Zinc Interactions with a Soluble Mutated Rat Amylin to Mimic Whole Human Amylin: An Experimental and Simulation Approach to Understand Stoichiometry,Speciation and Coordination of the Metal Complexes

Islet amyloid polypeptide (IAPP) is a hormone co-secreted with insulin and zinc from pancreatic β-cells. To overcome the low solubility of human IAPP, we characterized zinc complexes species formed with 1) a mutated form of rat-IAPP(1–37; R18 H) able to mimic the human IAPP, 2) the r-IAPP(1–37) and the IAPP(1–8) fragment. Stoichiometry, speciation and coordination features of zinc(II) complexes were unveiled by ESI-MS, potentiometry and NMR measurements combined with DFT and free-energy simulations. Mononuclear species start to form around pH 6; Zn²⁺ binds both His18 and N-amino terminus in rat-IAPP(1–37; R18 H). The in silico study allows us to assess not only a structured turn compact domain in r-IAPP(1–37) and r-IAPP(1–37; R18 H) featured by a different free energy barrier for the transition from the compact to elongated conformation upon the coordination of Zn²⁺, but also to bring into light a coordination shell further stabilized by noncovalent interactions.     

Preparation,physicochemical characterization and biological activity evaluation of some inclusion complexes containing artesunate

Journal of Thermal Analysis and Calorimetry - The use of cyclodextrins as carrier molecules is currently highly researched since they can improve not only the apparent water solubility and...     

On neighborhoods and partial sums of certain meromorphic multivalent functions

The main purpose of the present paper is to derive some properties associated with the neighborhoods and partial sums of a certain class of meromorphic multivalent functions.     

Effects of plant lactones on the production of biofilm of Pseudomonas aeruginosa

Sixteen plant sesquiterpene lactones, thirteen from four species of the Family Asteraceae, and three from a species of Hepaticae, as well as seven annonaceous acetogenins isolated from the seeds of the tropical tree Annona cherimolia (Family Annonaceae), were evaluated for their ability to inhibit or stimulate the production of biofilm by a strain of Pseudomonas aeruginosa. The tested compounds carry a gamma-lactone moiety in their structures. This structural feature is similar to the lactone moiety present in N-acyl homoserine lactones, compounds that play the important role of "quorum sensors" in the mechanisms of biofilm formation observed in many gram-negative bacteria. A special assay was employed to evaluate the influence of the tested plant compounds to inhibit or stimulate the production of biofilm in a P. aeruginosa wild strain. Most of the tested compounds affected the biofilm formation mechanism. Six sesquiterpene lactones isolated from Acanthospermum hispidum and one from Enydra anagallis as well as an acetogenin from Annona cherimolia strongly inhibited (69-77%) the biofilm formation when incorporated to a bacterial culture at a concentration of 2.5 microg/ml. However, one of the acetogenins, squamocin, stimulated the biofilm formation even at a concentration of 0.25 microg/ml. The study of substances affecting the biofilm formation can lead to the design of new strategies to control P. aeruginosa infections.     

ZnO-coated glass fibers for the analysis of trihalomethanes by headspace-solid phase microextraction-gas chromatography

Li₂O-ZrO₂-BaO-SiO₂ glass fibers were produced and their surfaces were coated with zinc oxide. The fibers’ surface morphology was examined by scanning electron microscopy and the zinc oxide layer was characterized by mapping the K_α and L_α lines of zinc by energy dispersive X-ray spectroscopy. The results indicated that a homogeneous and porous layer of ZnO was formed on the fibers’ surface. This layer was subjected to a simultaneous determination of trihalomethanes using headspace-solid phase microextraction-gas chromatography. The study was conducted after evaluating the ideal time of incubation (15 min), extraction (15 min) and desorption (10 min), as well as the effect of the addition of salt (15%, m/v) on the analytical response. A good linear dynamic range was observed individually for trihalomethanes aqueous solutions containing 20 μg L⁻¹ and 500 μg L⁻¹ of trichloromethane, 15 μg L⁻¹ and 250 μg L⁻¹ of dichlorobromomethane and dibromochloromethane and 10 μg L⁻¹ and 100 μg L⁻¹ of tribromomethane, with all the compounds showing correlation coefficients higher than 0.9900.     

Chemical Characterization of Flowers and Leaf Extracts Obtained from Turnera subulata and Their Immunomodulatory Effect on LPS-Activated RAW 264.7 Macrophages

The anti-inflammatory properties of Turnera subulata have been evaluated as an alternative drug approach to treating several inflammatory processes. Accordingly, in this study, aqueous and hydroalcoholic extracts of T. subulata flowers and leaves were analyzed regarding their phytocomposition by ultrafast liquid chromatography coupled to mass spectrometry, and their anti-inflammatory properties were assessed by an in vitro inflammation model, using LPS-stimulated RAW-264.7 macrophages. The phytochemical profile indicated vitexin-2-O-rhamnoside as an important constituent in both extracts, while methoxyisoflavones, some bulky amino acids (e.g., tryptophan, tyrosine, phenylalanine), pheophorbides, and octadecatrienoic, stearidonic, and ferulic acids were detected in hydroalcoholic extracts. The extracts displayed the ability to modulate the in vitro inflammatory response by altering the secretion of proinflammatory (TNF-α, IL-1β, and IL-6) and anti-inflammatory (IL-10) cytokines and inhibiting the PGE-2 and NO production. Overall, for the first time, putative compounds from T. subulata flowers and leaves were characterized, which can modulate the inflammatory process. Therefore, the data highlight this plant as an option to obtain extracts for phytotherapic formulations to treat and/or prevent chronic diseases.     

A Novel Strategy for Quantifying Clopidogrel Using Square‐wave Voltammetry and a Boron‐doped Diamond Film

The voltammetric behavior of clopidogrel bisulfate (CLO), an antiplatelet agent, was investigated for the first time in the literature on a cathodically pretreated boron‐doped diamond electrode (CP‐BDDE) using cyclic (CV) and square‐wave voltammetry (SWV). It was observed an anodic peak for CLO, suitable for analytical purposes, at about 1.15 V (vs. Ag/AgCl (3.0 mol L^?1 KCl)) by CV in Britton‐Robinson buffer solution (pH 5.0). On the physical‐chemical characterization of the interface phenomena, it was proved that electrode reaction of the analyte was controlled by a diffusion process. At optimized square‐wave parameters (pulse amplitude of 60 mV, frequency of 30 Hz and scan increment of 3 mV), the obtained analytical curve was linear for the CLO concentration range from 0.60 to 60.0 μmol L^?1, with a detection limit of 0.60 μmol L^?1. The simple, rapid and greener analytical method, based on CP‐BDDE electrochemical sensor, was successfully applied in real samples (pharmaceuticals and urine).     

Identification of adequate vehicles to carry nerve regeneration inducers using tubulisation

ABSTRACT: BACKGROUND: Axonal regeneration depends on many factors, such as the type of injury and repair, age, distance from the cell body and distance of the denervated muscle, loss of surrounding tissue and the type of injured nerve. Experimental models use tubulisation with a silicone tube to research regenerative factors and substances to induce regeneration. Agarose, collagen and DMEM (Dulbecco's modified Eagle's medium) can be used as vehicles. In this study, we compared the ability of these vehicles to induce rat sciatic nerve regeneration with the intent of finding the least active or inert substance. The experiment used 47 female Wistar rats, which were divided into four experimental groups (agarose 4%, agarose 0.4%, collagen, DMEM) and one normal control group. The right sciatic nerve was exposed, and an incision was made that created a 10 mm gap between the distal and proximal stumps. A silicone tube was grafted onto each stump, and the tubes were filled with the respective media. After 70 days, the sciatic nerve was removed. We evaluated the formation of a regeneration cable, nerve fibre growth, and the functional viability of the regenerated fibres. RESULTS: Comparison among the three vehicles showed that 0.4% agarose gels had almost no effect on provoking the regeneration of peripheral nerves and that 4% agarose gels completely prevented fibre growth. The others substances were associated with profuse nerve fibre growth. CONCLUSIONS: In the appropriate concentration, agarose gel may be an important vehicle for testing factors that induce regeneration without interfering with nerve growth.