Bimodal Fluorescence/Magnetic Resonance Molecular Probes with Extended Spin Lifetimes

Bimodal molecular probes combining nuclear magnetic resonance (NMR) and fluorescence have been widely studied in basic science, as well as clinical research. The investigation of spin phenomena holds promise to broaden the scope of available probes allowing deeper insights into physiological processes. Herein, a class of molecules with a bimodal character with respect to fluorescence and nuclear spin singlet states is introduced. Singlet states are NMR silent but can be probed indirectly. Symmetric, perdeuterated molecules, in which the singlet states can be populated by vanishingly small electron-mediated couplings (below 1 Hz) are reported. The lifetimes of these states are an order of magnitude longer than the longitudinal relaxation times and up to four minutes at 7 T. Moreover, these molecules show either aggregation induced emission (AIE) or aggregation caused quenching (ACQ) with respect to their fluorescence. In the latter case, the existence of excited dimers, which are proposed to use in a switchable manner in combination with the quenching of nuclear spin singlet states, is observe

Probiotics action on gliadin sequences relevant to gluten sensitivity

The Celiac disease in genetically predisposed individuals is mainly induced by specific repetitive sequences in gliadins (PQPYP). This autoimmune disease stems from the interaction between toxic sequences and lamina propria cells, that is relevant also to other forms of gluten sensitivity. Specific endo-esoprolinase were isolated from lactic acid bacteria, suggesting possible practical applications. The ability of some probiotics at removing "toxic" celiac sequences was investigated, at first by assessing the presence and level of endo- and eso-prolinase activity in some of the most popular probiotic bacteria. Significant activities were detected in Lactobacillus and Bifidum species, as well as in the probiotic Escherichia coli Niessle 1917. On the basis of prolinase data, we investigated by mass spectroscopy the removal of "toxic" sequences in gliadin. A complete disappearance of these sequences was observed only with Escherichia coli Niessle 1917. Among the Bifidus and Lactobacillus species, only B. bifidum MIMBb23SG and L. acidophilus LA5 showed a significant decrease in the "toxic" sequences. All together, this study suggests a potential use of lactic bacteria to lower gluten response in sensitive individuals, including celiacs and gluten-sensitive

Comparative analysis of eliciting capacity of raw and roasted peanuts: the role of gastrointestinal digestion

This study investigated the simultaneous impact of food matrix and processing on the food allergy eliciting capacity of peanuts in a physiologically relevant context. Whole raw and roasted peanuts were subjected to in vitro digestion combining the harmonized oral-gastric-duodenal digestion models with brush border membrane enzymes (BBM) to simulate the jejunal degradation of peptides. SDS-PAGE and HPLC analysis showed that roasting increased digestibility of peanuts and this trend was even more evident after BBM degradation. The eliciting properties of raw and roasted peanuts were assessed by Rat Basophil Leukemia assay in the presence of sera from peanut-allergic patients. As general features, the BBM digestion reduced allergenicity of roasted peanuts compared to the raw counterpart, suggesting that intestinal peptidases effectively contribute to further destroy specific domains of peanut allergens. These findings provide new and more realistic insights in the stability of peanut allergens within their natural matrix

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

Direct arylations on water: synthesis of 2,5-disubstituted oxazoles balsoxin and texaline

An efficient two-step palladium catalysed synthesis of 2,5-disubstituted oxazoles is reported

Percutaneous ethanol injection for treatment of solid, cystic and autonomous thyroid nodules

Percutaneous ethanol injection (PEI) guided by ultrasound has been used for the treatment of cystic, solid and autonomous thyroid nodules. We present our experience in the treatment of 50 patients with thyroid nodules: 26 solid, 17 cystic and 7 autonomous (AN). Patients were evaluated 1 week, 1, 3, and 6 months and 1 year after PEI. After one year, solid nodules showed a mean 74% volume reduction, and cysts a volume reduction of 92%, with no recurrences. After one year, 5 patients with AN reached clinical and laboratory euthyroidism; the other 2 also became euthyroid, but with subnormal TSH. Recurrence of thyrotoxicosis was not observed and mean nodular reduction was 66%. The procedure was well tolerated by all patients. The results confirm that PEI is a good therapeutic alternative for reduction of solid and cystic thyroid nodules and for the treatment of autonomous nodules.A injeção percutânea de etanol (IPE) guiada por ultra-som tem sido utilizada para o tratamento de nódulos tiroidianos autônomos, sólidos e císticos. Apresentamos nossa experiência em 50 pacientes tratados, sendo 26 portadores de nódulos sólidos, 17 de nódulos císticos e 7 de nódulos autônomos (NA). Avaliamos os pacientes 1 semana, 1 mês, 3 meses, 6 meses e 1 ano após a IPE. Após 1 ano, os nódulos sólidos reduziram a 74% do volume inicial, os císticos diminuíram 92% sem apresentar recidivas. Um ano após o tratamento dos nódulos autônomos, 5 pacientes estavam em eutiroidismo clínico e laboratorial e 2 em eutiroidismo mas com TSH subnormal. Não houve recorrência da tirotoxicose e a redução nodular foi de 66%. O procedimento foi bem tolerado por todos. Os resultados confirmam que a IPE é uma boa alternativa terapêutica para redução dos nódulos tiroidianos císticos e sólidos e no tratamento dos nódulos autônomos.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de MedicinaUNIFESP, EPM, Depto. de MedicinaSciEL

The EPRL intertwiners and corrected partition function

Do the SU(2) intertwiners parametrize the space of the EPRL solutions to the simplicity constraint? What is a complete form of the partition function written in terms of this parametrization? We prove that the EPRL map is injective for n-valent vertex in case when it is a map from SO(3) into SO(3)xSO(3) representations. We find, however, that the EPRL map is not isometric. In the consequence, in order to be written in a SU(2) amplitude form, the formula for the partition function has to be rederived. We do it and obtain a new, complete formula for the partition function. The result goes beyond the SU(2) spin-foam models framework.Comment: RevTex4, 15 pages, 5 figures; theorem of injectivity of EPRL map correcte

Quaternionic Electroweak Theory

We explicitly develop a quaternionic version of the electroweak theory, based on the local gauge group $U(1, q)_{L}\mid U(1, c)_{Y}$. The need of a complex projection for our Lagrangian and the physical significance of the anomalous scalar solutions are also discussed.Comment: 12 pages, Revtex, submitted to J. Phys.