Carbonic Anhydrase Activators. Part 191 Spectroscopic and Kinetic Investigations for the Interaction of Isozymes I and II With Primary Amines

The interactions of Zn(II)- and Co(II)-substituted carbonic anhydrase (CA) isozymes I and II with amine type activators such as histamine, serotonin, phenetylamine dopamine and benzylhydrazine have been investigated kinetically, and spectroscopically. All of such activators are of the non-competitive type towards CO2 hydration and 4-nitrophenylacetate hydrolysis for both human isozymes (HCA I and HCA II). The electronic spectra of the adducts of Co(II)CA with amine activators are similar to the spectrum of the previously reported Co(II)CAII-phenol adduct, the only known competitive inhibitor towards CO2 hydration, where the phenol molecule binds into the hydrophobic pocket of the active site. This is a direct spectroscopic evidence that the activator molecules bind within the active site, but not directly to the metal ion. Recent X-ray crystallographic data for the adduct of HCA II with histamine show that the activator molecule is bound at the entrance of the active site cavity, near to residues His 64, Asn 62 and Gln 92, where actively aids in shuttling protons between the active site and the environment. Similar arrangements probably occur for the other activators reported in the present paper

Complexes With Biologically Active Ligands. Part 91 Metal Complexes of 5-Benzoylamino- and 5-(3-Nitrobenzoyl-Amino)-1,3,4-Thiadiazole-2-Sulfonamide as Carbonic Anhydrase Inhibitors

Complexes containing the anions of 5-benzoylamido-1,3,4-thiadiazole-2-sulfonamide and 5-(3-nitro-benzoylamido)-1,3,4-thiadiazole-2-sulfonamid as ligands, and V(IV); Cr(III); Fe(III); Co(II); Ni(II); Cu(II) and Ag(I) were synthesized and characterized by standard procedures (elemental analysis; IR, electronic, and EPR spectroscopy; TG, magnetic and conductimetric measurements). The original sulfonamides and their metal complexes are strong inhibitors of two carbonic anhydrase (CA) isozymes, CA I and II

Carbonic Anhydrase Inhibitors. Part 551 Metal Complexes of 1,3,4-Thiadiazole-2-Sulfonamide Derivatives: In Vitro Inhibition Studies With Carbonic Anhydrase Isozymes I, II and IV

Coordination compounds of 5-chloroacetamido-1,3,4-thiadiazole-2-sulfonamide (Hcaz) with V(IV), Cr(lll), Fe(ll), Co(ll), Ni(ll) and Cu(ll) have been prepared and characterized by standard procedures (spectroscopic, magnetic, EPR, thermogravimetric and conductimetric measurements). Some of these compounds showed very good in vitro inhibitory properties against three physiologically relevant carbonic anhydrase (CA)isozymes, i.e., CA I, II, and IV. The differences between these isozymes in susceptibility to inhibition by these metal complexes is discussed in relationship to the characteristic features of their active sites, and is rationalized in terms useful for developing isozyme-specific CA inhibitors

Carbonic Anhydrase Interaction With Lipothioars Enites: A Novel Class of Isozymes I and II Inhibitors

The interaction of carbonic anhydrase (CA) isozymes I and II with a series of As(III) derivatives, dialkyl and diaryl rac-2,3-dimyristoyloxypropyldithioarsonites, was investigated kinetically and spectrophotometrically, utilizing the native and Co(II)-substituted enzymes. Depending on the substitution pattern at the -As(SR)2 moiety of the investigated derivatives, inactive compounds were found for R = phenyl or naphthyl, and active ones for derivatives containing carboxyl groups (R = CH2COOH, cysteinyl and glutathionyl). Together with the arsonolipids previously investigated, the active compounds of this series - the "lipothioarsenites"- constitute a novel class of CA inhibitors that bind to the metal ion within the enzyme active site, as proved by changes in the electronic spectra of adducts of such inhibitors with Co(II)CA

Complexes With Biologically Active Ligands. Part 111. Synthesis and Carbonic Anhydrase Inhibitory Activity of Metal Complexes of 4,5-Disubstituted-3-Mercapto-1,2,4-Triazole Derivatives

Complexes containing five 4,5-disubstituted-3-mercapto-1,2,4-triazoles and Zn(II), Hg(II) and Cu(I) were synthesized and characterized by standard procedures (elemental analysis; IR, electronic and NMR spectroscopy, conductimetry and TG analysis). Both the thione as well as the thiolate forms of the ligands were evidenced to interact with the metal ions in the prepared complexes. The original mercaptans and their metal complexes behave as inhibitors of three carbonic anhydrase (CA) isozymes, CA I, II and IV, but did not lower intraocular pressure in rabbits in animal models of glaucoma

Effect of platelet lysate on human cells involved in different phases of wound healing

Background Platelets are rich in mediators able to positively affect cell activity in wound healing. Aim of this study was to characterize the effect of different concentrations of human pooled allogeneic platelet lysate on human cells involved in the different phases of wound healing (inflammatory phase, angiogenesis, extracellular matrix secretion and epithelialization). Methodology/Principal Findings Platelet lysate effect was studied on endothelial cells, monocytes, fibroblasts and keratinocytes, in terms of viability and proliferation, migration, angiogenesis, tissue repair pathway activation (ERK1/2) and inflammatory response evaluation (NFκB). Results were compared both with basal medium and with a positive control containing serum and growth factors. Platelet lysate induced viability and proliferation at the highest concentrations tested (10% and 20% v/v). Whereas both platelet lysate concentrations increased cell migration, only 20% platelet lysate was able to significantly promote angiogenic activity (p<0.05 vs. control), comparably to the positive control. Both platelet lysate concentrations activated important inflammatory pathways such as ERK1/2 and NFκB with the same early kinetics, whereas the effect was different for later time-points. Conclusion/Significance These data suggest the possibility of using allogeneic platelet lysate as both an alternative to growth factors commonly used for cell culture and as a tool for clinical regenerative application for wound healing

Reviewing the problem of the U(1) axial symmetry and the chiral transition in QCD

We discuss the role of the U(1) axial symmetry for the phase structure of QCD at finite temperature. We expect that, above a certain critical temperature, also the U(1) axial symmetry will be (effectively) restored. We will try to see if this transition has (or has not) anything to do with the usual chiral transition: various possible scenarios are discussed. In particular, supported by recent lattice results, we analyse a scenario in which a U(1)-breaking condensate survives across the chiral transition. This scenario can be consistently reproduced using an effective Lagrangian model. The effects of the U(1) chiral condensate on the slope of the topological susceptibility in the full theory with quarks are studied: we find that this quantity (in the chiral limit of zero quark masses) acts as an order parameter for the U(1) axial symmetry above the chiral transition. Further information on the new U(1) chiral order parameter is derived from the study (at zero temperature) of the radiative decays of the pseudoscalar mesons in two photons: a comparison of our results with the experimental data is performed.Comment: 27 pages, LaTeX file. Completely revised version including new references and new comments on the result

Intra-swash hydrodynamics and sediment flux for dambreak swash on coarse-grained beaches

The paper reports on dambreak-type swash experiments in which intra-swash hydrodynamics and sediment flux are measured for swash on a coarse sand beach and a gravel beach. Flow velocity and depth are measured using PIV and LIF respectively; the intra-swash sediment flux is measured using sediment traps. Comparison of measured hydrodynamics with the immobile, permeable bed experiments of Kikkert et al. (2013) indicates that bed mobility impacts on the swash hydrodynamics, reducing the maximum run-up by approximately 8% for both beaches, compared to the maximum run-up on the corresponding immobile beach. The measured intra swash sediment flux at a given location is characterised by high flux at the moment of bore arrival, followed by rapid decay during uprush, becoming zero at some time before flow reversal. For the gravel beach, the backwash sediment flux is negligibly small, while for the sand beach the backwash flux increases slowly as the flow accelerates down the beach, and peaks at about the time of maximum backwash velocity. Intra-swash sediment flux calculated using the Meyer-Peter and Müller bed load transport formula, with measured hydrodynamics as input and bed shear stress estimated using both the Swart and Colebrook formulae, is within a factor 2 of the measured intra-swash flux. The agreement between the calculated and measured flux is better for the sand beach than for the gravel beach, and better for uprush than for backwash. For the sand beach there is good agreement between calculated and measured total uprush and total backwash sediment volumes. The agreement is less good for the gravel beach, for which calculated and measured uprush volumes show a similar trend but the calculated backwash volumes over-estimate the (negligible) volumes observed in the experiments

Legionnaires' disease associated with macular rash: two cases.

Legionnaires' disease is an acute bacterial infection, generally sustained by Legionella pneumophila, which involves primarily the lower respiratory tract, although it is often associated with multi-systemic extrapulmonary manifestations. Afflicted patients may sometimes have gastrointestinal symptoms, liver function abnormalities, renal failure or central nervous system complications, while cutaneous manifestations are very uncommon and may include erythematous, maculopapular or petechial skin lesions. Pathogenesis of skin involvement in the setting of Legionnaires' disease is still uncertain, but may involve toxic or immunological mechanisms. Two exceptional cases of Legionella pneumonia complicated by diffuse, macular rash in two adult women are described, in association with severe peripheral polyneuropathy and flaccid quadriplegia in one case