Conservation laws with discontinuous flux

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Physicochemical and biological properties of natural and synthetic C-22 and C-23 hydroxylated bile acids.

In order to define the effect of a side chain hydroxy group on bile acid (BA) physicochemical and biological properties, 23-hydroxylated bile acids were synthesized following a new efficient route involving the alpha-oxygenation of silylalkenes. 22-Hydroxylated bile acids were also studied. The synthesized bile acids included R and S epimers of 3 alpha,7 alpha,23-trihydroxy-5 beta-cholan-24-oic acid (23R epimer: phocaecholic acid), 3 alpha,12 alpha,23-trihydroxy-5 beta-cholan-24-oic (23R epimer: bitocholic acid), and 3 alpha,7 beta,23-trihydroxy-5 beta-cholan-24-oic acid. A 3 alpha,7 alpha,22-trihydroxy-5 beta-cholan-24-oic acid (haemulcholic acid) was also studied. The presence of a hydroxy group on the side chain slightly modified the physicochemical behavior in aqueous solution with respect to common BA: the critical micellar concentration (CMC) and the hydrophilicity were similar to naturally occurring trihydroxy BA such as cholic acid. The pKa value was lowered by 1.5 units with respect to common BA, being 3.8 for all the C-23 hydroxy BA. C-22 had a higher pKa (4.2) as a result of the increased distance of the hydroxy group from the carboxy group. When the C-23 hydroxylated BA were intravenously administered to bile fistula rats, they were efficiently recovered in bile (more than 80% unmodified) while the corresponding analogs, lacking the 23- hydroxy group, were almost completely glycine- or taurine-conjugated. On the other hand, the C-22 hydroxylated BA were extensively conjugated with taurine and less than 40% of the administered dose was secreted without being conjugated. In the presence of intestinal bacteria, they were mostly metabolized to the corresponding 7-dehydroxylated compound similar to common BA with the exception of bitocholic acid which was relatively stable. The presence of a hydroxy group at the C-23 position increased the acidity of the BA and this accounted for poor absorption within the biliary tree and efficient biliary secretion without the need for conjugation. 3 alpha,7 beta-23 R/S trihydroxy-5 beta-cholan-24-oic acids could improve the efficiency of ursodeoxycholic acid (UDCA) for gallstone dissolution or cholestatic syndrome therapy, as it is relatively hydrophilic and efficiently secreted into bile without altering the glycine and taurine hepatic pool

Antioxidant activity of phenolic extracts from different cultivars of Italian onion (Allium cepa) and relative human immune cell proliferative induction

The total antioxidant activity (TAC) may vary considerably between onion cultivars. Immunological effects of onion phenolic compounds are still underestimated.The objective of this study is to determine the total phenol content (TPC) and the relative TAC of three Allium cepa L. (Liliaceae) onion cultivars cultivated in Cannara (Italy): Rossa di Toscana, Borettana di Rovato, and Dorata di Parma, and to evaluate the phenol extracts ability to induce human immune cell proliferation.TPC was determined by the Folin-Ciocalteu method, TAC with FRAP, TEAC/ABTS, and DPPH methods. Peripheral blood mononuclear cells from healthy human donors were incubated for 24 h at 37 °C with 1 ng/mL of phenolic extract in PBS, immunostained, and then analyzed by 4-color flow cytometry for the phenotypic characterization of T helper cells (CD4+ cells), cytotoxic T lymphocytes (CD8+ cells), T regulatory cells (CD25high CD4+ cells), and natural killer cells/monocytes (CD16+ cells).Rossa di Toscana displayed the highest TPC (6.61 ± 0.87 mg GA equivalents/g onion bulb DW) and the highest TAC with the experienced methods: FRAP, 9.19 ± 2.54 μmol Trolox equivalents/g onion bulb DW; TEAC/ABTS, 21.31 ± 0.41 μmol Trolox equivalents/g onion bulb DW; DPPH, 22.90 ± 0.01 μmol Trolox equivalents/g onion bulb DW. Incubation with Rossa di Toscana extract determined an increase in the frequency of the antitumor/anti-infection NK CD16+ immune cells (23.0 ± 0.4%).Content of health-promoting phenols and the deriving antioxidant and immunostimulating activity vary considerably among the investigated cultivars. Rossa di Toscana can be considered as a potential functional food

Omeprazole induces apoptosis in normal human polymorphonuclear leucocytes.

We investigated in vitro apoptosis in human polymorphonuclear neutrophils (PMN) induced by omeprazole. This drug, both in the native (OM) and acidified (OM-HCl) form, is a potent inducer of PMN apoptosis. The effect is time- and dose-dependent. OM-HCl is more efficient than OM in inducing PMN apoptosis. In fact, after 24 h incubation in vitro at 1×10 −4M OM-HCl induces apoptosis in 70% of the cell population compared to 37% induced by OM. Apoptosis induced by both forms of the drug is caspase dependent being significantly reduced by pretreating cells with the caspase 3 inhibitor (DEVDH-CHO). However, some differences in the apoptosis mechanisms between the two forms of the drug seem to exist because PMN treatment with the specific caspase 8 inhibitor (Z-IETD-FMK) only blocks OM-HCl mediated apoptosis. We observed cleavage of caspase 8 only in the cells incubated with OM-HCl while the executioner caspase 3 was activated with both forms of the drug. Furthermore, pretreatment with GM-CSF, a known activator of intracellular survival pathways in PMN, partially protected cells from OM-HCl induced apoptosis but did not contrast the apoptotic effect of OM. Cysteine cathepsin proteases also seem involved in the apoptotic mechanism of both drug forms since the specific inhibitor E64d gave a significant protection. To verify if OM-HCl induced apoptosis was dependent on the sulfenamide bound with the cell sulfhydryl groups we used molecules with thiol groups such as β-mercaptoethanol (β-ME) and reduced glutathione (GSH). Reactions of OM-HCl with cellular sulfhydryl groups are strongly involved in both the triggering and evolving phase of the apoptotic mechanism since significant protection from apoptosis was obtained when PMN were pretreated for 1h with β-ME (lipid-permeable) or GSH (lipid-impermeable). These results show that OM and OM-HCl induce apoptosis in human PMN and suggest that the second binds the sulfhydryl groups, present on the cell membrane, to then penetrate the cell thus causing a further significant increase in apoptosis. OM-induced PMN apoptosis during the treatment of gastric inflammatory disease could be an advantage for the resolution of the phlogosis state. However, this aspect should be further elucidated to assess the optimal therapeutical regimen for gastric diseases which are related to infective agents

VALIDATED PUNGENCY ASSESSMENT OF THREE ITALIAN ONION (ALLIUM CEPA L.) CULTIVARS

Abstract In the frame of a broad multidisciplinary study aimed at enlightening the peculiarities of three onion cultivars (Dorata di Parma, Borettana and Rossa di Toscana

Fusing Acoustic Ranges and Inertial Measurements in AUV Navigation: the Typhoon AUV at CommsNet13 Sea Trial

The paper presents some experimental results of autonomous underwater navigation, based on the fusion of acoustic and inertial measurements. The work is in the framework of the Thesaurus project, funded by the Tuscany Region, aiming at developing techniques for systematic exploration of marine areas of archaeological interest through a team of Autonomous Underwater Vehicles (AUVs). The test was carried out with one Typhoon vehicle, a 300m depth rated AUV with acoustic communication capabilities, during the CommsNet13 experiment, organized and scientifically coordinated by the NATO S&T Org. Ctr. for Maritime Research and Experimentation (CMRE, formerly NURC), with the participation of several research institutions. The fusion algorithm is formally casted into an optimal stochastic filtering problem, where the rough estimation of the vehicle position, velocity and attitude, are refined by using the depth measurement, the relative measurements available on the acoustic channel and the vehicle surge speed

Fast algorithms for the approximation of a fluid-dynamic

model on network

Combined monodimensional chromatographic approaches to monitor the presence of d-amino acids in cheese

The presence of d-amino acids (d-AAs) as a consequence of natural or artificial interventions such as ageing, microorganism action, preservative and conservative processes (alkali or heat treatment), is a scarcely treated aspect from the scientific community. It is also fully documented that even a minor degree of racemisation on the proteins' AAs is the cause of a reduced digestion of such proteins. Besides interfering with the regular metabolism of l-AAs, d-AAs can also contribute to the development of pathological conditions in humans. So far, nearly all the most important chromatographic techniques were applied to quantify d-AAs in foodstuffs. However, most of them rely upon pre- or post-column derivatization procedures, often combined with sophisticated analytical equipments. Differently, in this paper we propose an easy-to-set up combination of monodimensional chromatographic methods to monitor the variation of the d-Ala, d-Asp and d-Glu content in two commercially available Spanish cheese samples prepared from the same milk mixture and characterized by a different maturity time: no ripening and six months ripening. After the free amino acid mixture was extracted from the two cheese samples, an ion-pairing RP-HPLC achiral protocol was firstly optimized with the objective to avail of a method enabling the complete distinction of Ala, Asp, and Glu from all the other aminoacidic species in the two extracts. An ion-exchange-based chromatographic method was also optimized, thus allowing a profitable fractionation of the two aminoacidic mixtures. With such a procedure, less complex samples to be analyzed with a chiral ligand-exchange chromatography (CLEC) stationary phase based on S-trityl-. l-cysteine (. l-STC) units were obtained.The optimized CLEC conditions were then applied to the previously identified Ala, Asp and Glu containing fractions as well as to those including all the remaining species. For all the three compounds the enantiomeric excess (ee) was found to decrease passing from the ripened to the fresh cheese. As expected, the largest difference was found for Ala (ee value from 83.0% down to 20.5%), followed progressively by Asp (ee value from 90.5 to 75.0%) and Glu (ee value from 99.0 to 91.8%). © 2013 Elsevier Ltd.Peer Reviewe