New photoantimicrobial films composed of porphyrinated lipophilic cellulose esters

Porphyrinated cellulose laurate esters have been prepared in homogeneous DMA/LiCl medium by "one-pot, two-step" reactions starting from cellulose, protoporphyrin IX, and lauric acid and using a TsCl/Pyridine system. The plastic films obtained after casting were shown to display photobactericidal activity against Gram positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria. This new photobactericidal polymer has potential for industrial, medical, or household applications.     

Efficient oxidative modification of polysaccharides in water using H2O2 activated by iron sulfophthalocyanine

Selective and environmentally friendly oxidation of polysaccharides by hydrogen peroxide in the presence of iron tetrasulfophthalocyanine (FePcS) catalyst was studied in aqueous media. Oxidation under mild conditions led to the cleavage of the C–C bond of vicinal diols of glycoside units as a result of carbonyl and carboxyl formation. Optimized experimental conditions allowed oxidation of hydroxyethylcellulose (HEC), sodium carboxymethylcellulose (NaCMC), guar gum (GG), and inulin to the extent of 19, 30, 53, 23 carbonyl functions per 100 anhydroglucose units, respectively. Possible explanation for this relatively modest conversion is discussed. Over-oxidation phenomena appear to play an important role during the oxidation process.     

Glycosyl bis-porphyrin conjugates: synthesis and potential application in PDT

Syntheses of new glycosylated neutral and cationic porphyrin dimers linked at the meso-position via a flexible hydrocarbon chain are described. A detailed 1H and 13C NMR study allows their complete structural elucidation. The UV-visible, fluorescence and MALDI mass spectra are also presented. Photocytotoxicities of these compounds against K562 leukaemia cell line are compared to those of Photofrin II.     

Metabolomics identifies novel Hnf1alpha-dependent physiological pathways in vivo

Mutations in the HNF1A gene cause maturity-onset diabetes of the young type 3, one of the most common genetic causes of non-insulin-dependent (type 2) diabetes mellitus. Although the whole-body Hnf1a-null mouse recapitulates the low insulin levels and high blood glucose observed in human maturity-onset diabetes of the young type 3 patients, these mice also suffer from Laron dwarfism and aminoaciduria, suggesting a role for hepatocyte nuclear factor 1α (Hnf1α) in pathophysiologies distinct from non-insulin-dependent (type 2) diabetes mellitus. In an effort to identify pathways associated with inactivation of Hnf1α, an ultraperformance liquid chromatography coupled to mass spectrometry-based metabolomics study was conducted on urine samples from wild-type and Hnf1a-null mice. An increase in phenylalanine metabolites is in agreement with the known regulation of the phenylalanine hydroxylase gene by Hnf1α. This metabolomic approach also identified urinary biomarkers for three tissue-specific dysfunctions previously unassociated with Hnf1α function. 1) Elevated indolelactate coupled to decreased xanthurenic acid also indicated defects in the indole and kynurenine pathways of tryptophan metabolism, respectively. 2) An increase in the neutral amino acid proline in the urine of Hnf1a-null mice correlated with loss of renal apical membrane transporters of the Slc6a family. 3) Further investigation into the mechanism of aldosterone increase revealed an overactive adrenal gland in Hnf1a-null mice possibly due to inhibition of negative feedback regulation. Although the phenotype of the Hnf1a-null mouse is complex, metabolomics has opened the door to investigation of several physiological systems in which Hnf1α may be a critical regulatory component.     

Which population level environmental factors are associated with asthma,rhinoconjunctivitis and eczema? Review of the ecological analyses of ISAAC Phase One

The International Study of Asthma and Allergies in Childhood (ISAAC) Phase One showed large worldwide variations in the prevalence of symptoms of asthma, rhinoconjunctivitis and eczema, up to 10 to 20 fold between countries. Ecological analyses were undertaken with ISAAC Phase One data to explore factors that may have contributed to these variations, and are summarised and reviewed here.In ISAAC Phase One the prevalence of symptoms in the past 12 months of asthma, rhinoconjunctivitis and eczema were estimated from studies in 463,801 children aged 13 - 14 years in 155 centres in 56 countries, and in 257,800 children aged 6-7 years in 91 centres in 38 countries. Ecological analyses were undertaken between symptom prevalence and the following: Gross National Product per capita (GNP), food intake, immunisation rates, tuberculosis notifications, climatic factors, tobacco consumption, pollen, antibiotic sales, paracetamol sales, and outdoor air pollution.Symptom prevalence of all three conditions was positively associated with GNP, trans fatty acids, paracetamol, and women smoking, and inversely associated with food of plant origin, pollen, immunisations, tuberculosis notifications, air pollution, and men smoking. The magnitude of these associations was small, but consistent in direction between conditions. There were mixed associations of climate and antibiotic sales with symptom prevalence.The potential causality of these associations warrant further investigation. Factors which prevent the development of these conditions, or where there is an absence of a positive correlation at a population level may be as important from the policy viewpoint as a focus on the positive risk factors. Interventions based on small associations may have the potential for a large public health benefit.     

One step selective 5'-O-allylation of thymidine using microwave or ultrasound activation

An improved procedures for the synthesis of 5'-O-allylthymidine via one step selective allylation of thymidine using either ultrasound or microwave activation is described.     

Complete spectra of the far-red chemiluminescence of the oxygenase reaction of Mn2+-activated ribulose-bisphosphate carboxylase/oxygenase establish excited Mn2+ as the source

Chemiluminescence emitted by Mn(2+)-activated ribulose-1,5-bisphosphate carboxylase/oxygenase (rubisco) while catalyzing oxygenation was analyzed to clarify the source of the emission. Using dual detectors capturing radiation over a wide range of visible and infrared wavelengths, we tested for radiation from singlet O(2) decay and found it to be essentially absent (less than 0.1% of the total luminescence intensity). Spectra were determined between 647 and 885 nm with a very sensitive, charge-coupled detector-based spectrograph to detect differences in the emission spectra between rubiscos from bacterial and higher plant sources. All Mn(2+)-activated rubiscos emitted a broad, smooth spectrum of chemiluminescence, unchanging as the reaction progressed. The spectra from higher plant rubiscos (spinach and both the wild type and an L335V mutant from tobacco), all exhibited maxima at about 800 nm. However, Mn(2+)-activated rubisco from the bacterium, Rhodospirillum rubrum, emitted at shorter wavelengths (760 nm peak), demonstrating host ligand-field influences arising from aminoacyl residue differences and/or conformational changes caused by the absence of small subunits. The findings provide strong evidence that the chemiluminescence arises from an excited state of the active-site Mn(2+) that is produced during oxygenation. We propose that the Mn(2+) becomes excited by a one-electron exchange mechanism of oxygenation that is not available to Mg(2+)-activated rubisco.     

Cellular delivery of impermeable effector molecules in the form of conjugates with peptides capable of mediating membrane translocation.

Most molecules that are not actively imported by living cells are impermeable to cell membranes, including practically all macromolecules and even many small molecules whose physicochemical properties prevent passive membrane diffusion. The use of peptide vectors capable of transporting such molecules into cells in the form of covalent conjugates has become an increasingly attractive solution to this problem. Not only has this technology permitted the study of modulating intracellular target proteins, but it has also gained importance as an alternative to conventional cellular transfection with oligonucleotides. Peptide vectors derived from viral, bacterial, insect, and mammalian proteins endowed with membrane translocation properties have now been proposed as delivery vectors. These are discussed comprehensively and critically in terms of relative utility, applications to compound classes and specific molecules, and relevant conjugation chemistry. Although in most cases the mechanisms of membrane translocation are still unclear, physicochemical studies have been carried out with a number of peptide delivery vectors. Unifying and distinguishing mechanistic features of the various vectors are discussed. Until a few years ago speculations that it might be possible to deliver peptides, proteins, oligonucleotides, and impermeable small molecules with the aid of cellular delivery peptides not only to target cells in vitro, but in vivo, was received with scepticism. However, the first studies showing pharmacological applications of conjugates between macromolecules and peptide delivery vectors are now being reported, and therapies based on such conjugates are beginning to appear feasible.     

Detection of local structures in reduced unfolded bovine pancreatic trypsin inhibitor.

The structure of BPTI and reduced BPTI in concentrated guanidinium HCl (GUHCl) in the presence of glycerol has been probed by measurements of dynamic nonradiative excitation energy transfer between probes attached to its amino groups. Interprobe distance distributions were obtained from analysis of donor fluorescence decay curves and used to characterize local structures in unordered states of the protein. Site specifically fluorescently labeled BPTI derivatives (1-n)BPTI (n = 15, 20, 41, 46) were used, each carrying a 2-methoxy-naphthyl-1-methylenyl group (MNA) at the N-terminal amino group of arg1 and 7-(dimethylamino)-coumarin-4-yl-acetyl residue (DA-coum) at one of its epsilon-NH2 groups of the lysine side chains. Analysis of donor fluorescence decay kinetics gave the interprobe distance distributions in the native and denatured states. The N-terminal-segment, residues 1-15, is in an extended conformation (with an average interprobe distance of 34 +/- 2 A) in the native state. Upon unfolding by reduction with DTT or beta-mercapto ethanol in 6 M GUHCl/glycerol mixture, the conformation of this segment relaxed to a state characterized by a reduced average interprobe distance and a larger width of the distances distribution. The average distance between residues 1 and 26, i.e., between the N-terminus and the turn of the twisted beta sheet element (residues 18-35), increased upon unfolding. At -30 degrees C in the above solvent, the distribution between these two sites was probably composed of two conformational subpopulations. About 45 +/- 20% of the molecules were characterized by a short interprobe distance (like the native state) representing a compact conformation, and 55 +/- 20% of the molecules showed large interprobe distances representing an expanded (unfolded) conformation. Thus local structures seem to exist in reduced denatured BPTI even under denaturing conditions in 6 M GUHCl/glycerol mixtures. Some of those structures are unstable in guanidinium isothiocyanate (GUSCN). The method introduced here is suitable for probing local structures and very long range interactions in unfolded proteins and for search for folding initiation sites (FISs) and early folding intermediates.