16-Bromoepiandrosterone, an activator of the mammalian immune system, inhibits glucose 6-phosphate dehydrogenase from Trypanosoma cruzi and is toxic to these parasites grown in culture

Glucose 6-phosphate dehydrogenase (G6PDH) catalyzes the first step of the pentose-phosphate pathway which supplies cells with ribose 5-phosphate (R5P) and NADPH. R5P is the precursor for the biosynthesis of nucleotides while NADPH is the cofactor of several dehydrogenases acting in a broad range of biosynthetic processes and in the maintenance of the cellular redox state. RNA interference-mediated reduction of G6PDH levels in bloodstream-form Trypanosoma brucei validated this enzyme as a drug target against Human African Trypanosomiasis. Dehydroepiandrosterone (DHEA), a human steroidal pro-hormone and its derivative 16 alpha-bromoepiandrosterone (16BrEA) are uncompetitive inhibitors of mammalian G6PDH. Such steroids are also known to enhance the immune response in a broad range of animal infection models. It is noteworthy that the administration of DHEA to rats infected by Trypanosoma cruzi, the causative agent of Human American Trypanosomiasis (also known as Chagas` disease), reduces blood parasite levels at both acute and chronic infection stages. In the present work, we investigated the in vitro effect of DHEA derivatives on the proliferation of T. cruzi epimastigotes and their inhibitory effect on a recombinant form of the parasite`s G6PDH (TcG6PDH). Our results show that DHEA and its derivative epiandrosterone (EA) are uncompetitive inhibitors of TcG6PDH, with K(i) values of 21.5 +/- 0.5 and 4.8 +/- 0.3 mu M, respectively. Results from quantitative inhibition assays indicate 16BrEA as a potent inhibitor of TcG6PDH with an IC(50) of 86 +/- 8 nM and those from in vitro cell viability assays confirm its toxicity for T. cruzi epimastigotes, with a LD(50) of 12 +/- 8 mu M. In summary, we demonstrated that, in addition to host immune response enhancement, 16BrEA has a direct effect on parasite viability, most likely as a consequence of TcG6PDH inhibition. Crown Copyright (C) 2010 Published by Elsevier Ltd. All rights reserved.

THE PYROCHLORE SUPERGROUP OF MINERALS: NOMENCLATURE

A new scheme of nomenclature for the pyrochlore supergroup, approved by the CNMNC-IMA, is based on the ions at the A, B and Y sites. What has been referred to until now as the pyrochlore group should be referred to as the pyrochlore supergroup, and the subgroups should be changed to groups. Five groups are recommended, based on the atomic proportions of the B atoms Nb, Ta, Sb, Ti, and W. The recommended groups are pyrochlore, microlite, romite, betafite, and elsmoreite, respectively. The new names are composed of two prefixes and one root name (identical to the name of the group). The first prefix refers to the dominant anion (or cation) of the dominant valence [or H(2)O or rectangle] at the Y site. The second prefix refers to the dominant cation of the dominant valence [or H(2)O or rectangle] at the A site. The prefix "" keno-"" represents "" vacancy"". Where the first and second prefixes are equal, then only one prefix is applied. Complete descriptions are missing for the majority of the pyrochlore-supergroup species. Only seven names refer to valid species on the grounds of their complete descriptions: oxycalciopyrochlore, hydropyrochlore, hydroxykenomicrolite, oxystannomicrolite, oxystibiomicrolite, hydroxycalcioromite, and hydrokenoelsmoreite. Fluornatromicrolite is an IMA-approved mineral, but the complete description has not yet been published. The following 20 names refer to minerals that need to be completely described in order to be approved as valid species: hydroxycalciopyrochlore, fluornatropyrochlore, fluorcalciopyrochlore, fluorstrontiopyrochlore, fluorkenopyrochlore, oxynatropyrochlore, oxyplumbopyrochlore, oxyyttropyrochlore-(Y), kenoplumbopyrochlore, fluorcalciomicrolite, oxycalciomicrolite, kenoplumbomicrolite, hydromicrolite, hydrokenomicrolite, oxycalciobetafite, oxyuranobetafite, fluornatroromite, fluorcalcioromte, oxycalcioromite, and oxyplumboromite. For these, there are only chemical or crystalstructure data. Type specimens need to be defined. Potential candidates for several other species exist, but are not sufficiently well characterized to grant them any official status. Ancient chemical data refer to wet-chemical analyses and commonly represent a mixture of minerals. These data were not used here. All data used represent results of electron-microprobe analyses or were obtained by crystal-structure refinement. We also verified the scarcity of crystal-chemical data in the literature. There are crystalstructure determinations published for only nine pyrochlore-supergroup minerals: hydropyrochlore, hydroxykenomicrolite, hydroxycalcioromite, hydrokenoelsmoreite, hydroxycalciopyrochlore, fluorcalciopyrochlore, kenoplumbomicrolite, oxycalciobetafite, and fluornatroromite. The following mineral names are now discarded: alumotungstite, bariomicrolite, bariopyrochlore, bindheimite, bismutomicrolite, bismutopyrochlore, bismutostibiconite, calciobetafite, ceriopyrochlore-(Ce), cesstibtantite, ferritungstite, jixianite, kalipyrochlore, monimolite, natrobistantite, partzite, plumbobetafite, plumbomicrolite, plumbopyrochlore, stannomicrolite, stetefeldtite, stibiconite, stibiobetafite, stibiomicrolite, strontiopyrochlore, uranmicrolite, uranpyrochlore, yttrobetafite-(Y), and yttropyrochlore-(Y).

Zr- AND Ba-RICH MINERALS FROM THE PONTE NOVA ALKALINE MAFIC-ULTRAMAFIC MASSIF, SOUTHEASTERN BRAZIL: INDICATION OF AN ENRICHED MANTLE SOURCE

Zirconium- and Ba-rich minerals are found in gabbroic rocks from the Ponte Nova alkaline mafic-ultramafic massif in southeastern Brazil. The unusual mineralogical assemblage includes zirconolite, baddeleyite, Ba-rich alkali feldspar, and Ba- and Ti-rich biotite. Zirconolite of the Ponte Nova massif has higher levels of Zr (up to 1.172 apfu) than those registered in other terrestrial rocks and a prominent enrichment in the light rare-earth elements. Baddeleyite contains small quantities of Hf, Ti, and Fe. The Ba-rich alkali feldspar and Ba- and Ti-rich biotite contain up to 9.25 and 7.35 wt% BaO, respectively, and the biotite contains up to 12.01 wt% TiO(2). In the different intrusions of the Ponte Nova massif, such an unusual assemblage typifies the residual magma after the crystallization of clinopyroxene and olivine from previously enriched basanitic parental magma. The different trends of enrichments in REE and Th + U found for zirconolite of the intrusions of the Ponte Nova massif provide a better understanding of the variable degrees of enrichment of incompatible elements of the distinct gabbroic bodies. A lithospheric mantle source enriched in incompatible elements by the metasomatic action of volatile-rich fluids and with the presence of phlogopite or amphibole (or both) and other minor accessory phases could explain the presence of the Zr- and Ba-rich minerals in this gabbroic massif.

Chemical and radiological characterization of clay minerals used in pharmaceutics and cosmetics

Since the early days, clays have been used for therapeutic purposes. Nowadays, they are used as active ingredients or as excipient in formulations for a variety of purposes. Despite their wide use, little information is available in literature on their content of trace elements and radionuclides. The purpose of this study was to determine the elements (As, Ba, Br, Cs, Co, Cr, Eu, Fe, Hf, Hg, La, Lu, Rb, Sb, Sc, Sm, Ta, Tb, Yb, Zn, and Zr) and the radionuclides ((238)U, (232)Th, (226)Ra, (228)Ra, (210)Pb and (40)K) in Brazilian clays as well as the health and radiological implications of the use of these clays in pharmaceutical formulations. (C) 2011 Elsevier B.V. All rights reserved.

Controls of heavy minerals and grain size in a holocene regressive barrier (Ilha Comprida, southeastern Brazil)

Ilha Comprida is a regressive barrier island located in southeastern Brazil that was formed essentially by Quaternary sandy sediments. Ilha Comprida sediments were analyzed to assess heavy mineral indices and grain size variables. The spatial variation of heavy minerals and grain size was interpreted in terms of the present barrier dynamics and the barrier`s evolution since the Middle Holocene. These analyses allowed for the identification of the main factors and processes that control the variation of heavy minerals and grain size on the barrier. Rutile and zircon (RZi) and tourmaline and hornblende (THi) are significantly sensitive to provenance and exhibit the contributions of the Ribeira de Iguape River sediments, which reach the coast next to the northeastern end of Ilha Comprida. In addition to the influence of provenance, TZi responds mainly to hydraulic sorting processes. This agrees with a sediment transport pattern characterized by a divergence of two resultant net alongshore drifts southwest of the barrier. The sediments from the Ribeira de Iguape River reach the barrier directly through the river mouth and indirectly after temporary storage in the inner shelf. The combination of grain size and heavy mineral analyses is a reliable method for determining sediment transport patterns and provenance. (C) 2010 Elsevier Ltd. All rights reserved.

Grain size and heavy minerals of the Late Quaternary eolian sediments from the Imbituba-Jaguaruna coast, Southern Brazil: Depositional controls linked to relative sea-level changes

The stratigraphic subdivision and correlation of dune deposits is difficult, especially when age datings are not available. A better understanding of the controls on texture and composition of eolian sands is necessary to interpret ancient eolian sediments. The Imbituba-Jaguaruna coastal zone (Southern Brazil, 28 degrees-29 degrees S) stands out due to its four well-preserved Late Pleistocene (eolian generation 1) to Holocene eolian units (eolian generations 2, 3, and 4). In this study, we evaluate the grain-size and heavy-mineral characteristics of the Imbituba-Jaguartma eolian units through statistical analysis of hundreds of sediment samples. Grain-size parameters and heavy-mineral content allow us to distinguish the Pleistocene from the Holocene units. The grain size displays a pattern of fining and better sorting from generation 1 (older) to 4 (younger), whereas the content of mechanically stable (dense and hard) heavy minerals decreases from eolian generation 1 to 4. The variation in grain size and heavy-mineral content records shifts in the origin and balance (input versus output) of eolian sediment supply attributable mainly to relative sea-level changes. Dunefields submitted to relative sea-level lowstand conditions (eolian generation 1) are characterized by lower accumulation rates and intense post-depositional dissection by fluvial incision. Low accumulation rates favor deflation in the eolian system, which promotes concentration of denser and stable heavy minerals (increase of ZTR index) as well as coarsening of eolian sands. Dissection involves the selective removal of finer sediments and less dense heavy minerals to the coastal source area. Under a high rate of relative sea-level rise and transgression (eolian generation 2), coastal erosion prevents deflation through high input of sediments to the coastal eolian source. This condition favors dunefield growth. Coastal erosion feeds sand from local sources to the eolian system. including sands from previous dunefields (eolian generation 1) and from drowned incised valleys. Therefore, dunefields corresponding to transgressive phases inherit the grain-size and heavy-mineral characteristics of previous dunefields, leading to selective enrichment of finer sands and lighter minerals. Eolian generations 3 and 4 developed during a regressive-progradational phase (Holocene relative sea level highstand). The high rate of sediment supply during the highstand phase prevents deflation. The lack of coastal erosion favors sediment supply from distal sources (fluvial sediments rich in unstable heavy minerals). Thus, dunefields of transgressive and highstand systems tracts may be distinguished from dunefields of the lowstand systems tract through high rates of accumulation (low deflation) in the former. The sediment source of the transgressive dunefields (high input of previously deposited coastal sands) differs from that of the highstand dunefields (high input of fluvial distal sands). Based on this case study, we propose a general framework for the relation between relative sea level, sediment supply and the texture and mineralogy of eolian sediments deposited in siliciclastic wet coastal zones similar to the Imbituba-Jaguaruna coast (C) 2009 Elsevier B.V. All rights reserved.

Effects of Micelles and Vesicles on the Oximolysis of p-Nitrophenyl Diphenyl Phosphate: A Model System for Surfactant-Based Skin-defensive Formulations against Organophosphates

The rates of oximolysis of p-nitrophenyl diphenyl phosphate (PNPDPP) by Acetophenoxime; 10-phenyl-10-hydi-oxyiminodecanoic acid; 4-(9-carboxynonanyl)-1-(9-carboxy-1-hydroyiminononanyl) benzene; 1-dodecyl-2-[(hydroxyimino)methyl]-pyridinium chloride (IV) and N-methylpyridinium-2-aldoxime chloride were determined in micelles of N-hexadecyl-N,N,N-trimethylammonium chloride (CTAC), N-hexadecyl-N,N-dimethylammonium propanesulfonate and dioctadecyldimethylammonium chloride (DODAC) vesicles. The effects of CTAC micelles and DODAC vesicles on the rates of oxymolysis of O,O-Diethyl O-(4-nitrophenyl) phosphate (paraoxon) by oxime IV were also determined. Analysis of micellar and vesicular effects on oximolysis of PNPDPP, using pseudophase or pseudophase with explicit consideration of ion exchange models, required the determination of the aggregate`s effects on the pK(a), of oximes and on the rates of PNPDPP hydrolysis. All aggregates increased the rate of oximolysis of PNPDPP and the results were analyzed quantitatively. In particular, DODAC vesicles catalyzed the reaction and increased the rate of oximolysis of PNPDPP by IV several million fold at pH`s compatible with pharmaceutical formulations. The rate increase produced by DODAC vesicles on the rate of oximolysis paraoxon by IV demonstrates the pharmaceutical potential of this system, since the substrate is used as an agricultural defensive agent and the surfactant is extensively employed in cosmetic formulations. (C) 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:1040-1052, 2009

Heterodinuclear Fe(III)Zn(II)-Bioinspired Complex Supported on 3-Aminopropyl Silica. Efficient Hydrolysis of Phosphate Diester Bonds

Presented herein is the synthesis and characterization of a new Fe(III)Zn(II) complex containing a Fe(III)-bound phenolate with a carbonyl functional group, which was anchored to 3-aminopropylfunctionalized silica as the solid support. The catalytic efficiency of the immobilized catalyst in the hydrolysis of 2,4-bis (dinitrophenyl) phosphate is comparable to the homogeneous reaction, and the supported catalyst can be reused for subsequent diester hydrolysis reactions.

Polyaniline/layered zirconium phosphate nanocomposites: Secondary-like doped polyaniline obtained by the layer-by-layer technique

In the present work, nanocomposites of polyaniline (PANI) and layered alpha-Zr(HPO4)(2).H2O (alpha-ZrP) were prepared using two different approaches: (i) the in situ aniline polymerization in the presence of the layered inorganic material and (ii) the layer-by-layer (LBL) assembly using an aqueous solution of the polycation emeraldine salt (ES-PANI) and a dispersion of exfoliated negative slabs of alpha-ZrP. These materials were characterized spectroscopically using mainly resonance Raman scattering at four exciting radiations and electronic absorption in the UV-VIS-NIR region. Structural and textural characterizations were carried out using powder X-ray diffraction (XRD) and scanning electron microscopy (SEM). The polymer obtained by the in situ aniline polymerization is located primarily in the external surface of the inorganic material although aniline monomers were intercalated between alpha-ZrP interlayer regions before oxidative polymerization. Through resonance Raman spectroscopy, it was observed that the formed polymer has semiquinone units (ES-PANI) and also azo bonds (-N = N-), showing that this method results in a polymer with a different structure from the usual ""head-to-tail"" ES-PANI. The LBL assembly of pre-formed ES-PANI and exfoliated alpha-ZrP particles produces homogeneous films with reproducible deposition from layer to layer, up to 20 bilayers. Resonance Raman (lambda(0) = 632.8 nm) spectrum of PANI/ZrP LBL film shows an enhancement in the intensity of the polaronic band at 1333 cm(-1) (nu C-N center dot+) and the decrease of the band intensity at 1485 cm(-1) compared to bulk ES-PANI. Its UV-VIS-NIR spectrum presents an absorption tail in the NIR region assigned to delocalized free charge carrier. These spectroscopic features are characteristic of highly conductive secondary doped PANI suggesting that polymeric chains in PANI/ZrP LBL film have a more extended conformation than in bulk ES-PANI.

Expression, purification and kinetic characterization of His-tagged glyceraldehyde-3-phosphate dehydrogenase from Trypanosoma cruzi

Trypanosomes are flagellated protozoa responsible for serious parasitic diseases that have been classified by the World Health Organization as tropical sicknesses of major importance. One important drug target receiving considerable attention is the enzyme glyceraldehyde-3-phosphate dehydrogenase from the protozoan parasite Trypanosoma cruzi, the causative agent of Chagas disease (T. cruzi Glyceraldehyde-3-phosphate dehydrogenase (TcGAPDH); EC 1.2.1.12). TcGAPDH is a key enzyme in the glycolytic pathway of T. cruzi and catalyzes the oxidative phosphorylation of D-glyceraldehyde-3-phosphate (G3P) to 1,3-bisphosphoglycerate (1,3-BPG) coupled to the reduction of oxidized nicotinamide adenine dinucleotide, (NAD(+)) to NADH, the reduced form. Herein, we describe the cloning of the T. cruzi gene for TcGAPDH into the pET-28a(+) vector, its expression as a tagged protein in Escherichia coli, purification and kinetic characterization. The His(6)-tagged TcGAPDH was purified by affinity chromatography. Enzyme activity assays for the recombinant His(6)-TcGAPDH were carried out spectrophotometrically to determine the kinetic parameters. The apparent Michaelis-Menten constant (K(M)(app)) determined for D-glyceraldehyde-3-phosphate and NAD(+) were 352 +/- 21 and 272 +/- 25 mu M, respectively, which were consistent with the values for the untagged enzyme reported in the literature. We have demonstrated by the use of Isothermal Titration Calorimetry (ITC) that this vector modification resulted in activity preserved for a higher period. We also report here the use of response surface methodology (RSM) to determine the region of optimal conditions for enzyme activity. A quadratic model was developed by RSM to describe the enzyme activity in terms of pH and temperature as independent variables. According to the RMS contour plots and variance analysis, the maximum enzyme activity was at 29.1 degrees C and pH 8.6. Above 37 degrees C, the enzyme activity starts to fall, which may be related to previous reports that the quaternary structure begins a process of disassembly. (C) 2010 Elsevier Inc. All rights reserved.

Nature of new order rights to minerals : a rubikian exercise since passing the mayday rubicon with a cubic zirconium?

The Mineral and Petroleum Resources Development Act 28 of 2002 has created new categories of rights to "minerals" that may be granted to applicants by the Minister of Minerals and Energy. In this article the nature of these rights will be examined. The legislature has labelled prospecting rights and mining rights to minerals as limited real rights in the MPRD Act. The remaining rights to minerals are not labelled. Provision is made for registration or recording rights in the revived Mining Titles Registration Act 16 of 1967 (as amended). Registered rights are claimed to constitute a limited real right binding against third parties. Discrepancies and contradictions regarding the nature of rights to minerals are created by the two statutes. It is concluded that only upon clarification of the provisions of the two sister statutes, would the nature of rights to minerals be more evident. The proposed amendment of section 5(1) of the MPRD Act would be in line with property doctrine based upon the common law and is to be welcomed.

"Minerals", "petroleum" and "operations" in the Mineral and Petroleum Resources Development Act 28 of 2002 : a geologist as devil's advocate for a change? "

This article examines the meaning of "minerals", petroleum, "operations" and activities in relation to such substances to determine the ambit of the application of the Minerals and Petroleum Resources Development Act 28 of 2002, the type of rights necessary for such operations and activities and the ambit of these rights. The examination of the meaning of these concepts takes place with reference to prior definitions in statutes and also from a natural science and geology perspective. An attempt is made to show that the legal definitions do no always correspond with the geological meanings and the meanings on the ground. It is questioned whether in recent legislation why more reliance is not placed on input from geologists in the field.

Microstructures and bond strengths of the calcium phosphate coatings formed on titanium from different simulated body fluids

Calcium phosphate (Ca-P) coatings were deposited on Ti substrates by a biomimetic method from m-SBF and 10× SBF, respectively. Comparative study of microstructures and bond strengths of the Ca-P coatings deposited from those different SBFs was carried out. Effect of the surface roughness of the substrates on the bond strength of the Ca-P coatings was also studied. Scanning electron microscopy (SEM), X-ray diffractometry (XRD), Fourier transformed infrared spectroscopy (FTIR), inductive coupled plasma spectrometry (ICP) and thermogravimetry (TG) were used to characterize the Ca-P coatings. The bond strengths between the coatings and Ti substrates were measured using an adhesive strength test. Results indicated that the ionic concentrations of the SBFs and the surface roughness of the substrate had a significant influence on the formation, morphology and bond strength of the Ca-P precipitates. The induction period of time to deposit a complete Ca-P layer from the m-SBF is much longer, but the Ca-P coating is denser and has higher bond strength than that formed from the 10× SBF. The Ti with a surface roughness of R_a 0.64 µm and R_z 2.81 µm favoures the formation of a compact Ca-P coating from the m-SBF with the highest bond strength of approximately 15.5 MPa.