Development of Mucoadhesive Gel Microbicide to Target Mucosal HIV Reservoirs

The wide use of microbicide is mainly depends on its effectiveness, less frequent application, ready availability and most importantly cost. The aim of this work was to develop affordable microbicide mucoadhesive gel formulation of synthetic anti HIV drug, stavudine and to characterise it in terms of its physical properties, mucoadhesiveness and spreadability. The purpose of the present study was also to compare different dissolution media used for in vitro release of vaginal dosage form. The gels were tested for antimicrobial, spermicidal and anti-HIV activity. Gels prepared using Carbopols and Polycarbophil were transparent and homogenous and had excellent mucoadhesion index - and showed fast drug release profile. Gels showed very good antimicrobial action against pathological microorganism

Conserved Residues R420 and Q428 in a Cytoplasmic Loop of the Citrate/Malate Transporter CimH of Bacillus subtilis Are Accessible from the External Face of the Membrane

CimH of Bacillus subtilis is a secondary transporter for citrate and malate that belongs to the 2-hydroxycarboxylate transporter (2HCT) family. Conserved residues R143, R420, and Q428, located in putative cytoplasmic loops and R432, located at the cytoplasmic end of the C-terminal transmembrane segment XI were mutated to Cys to identify residues involved in binding of the substrates. R143C, R420C, and Q428C revealed kinetics similar to those of the wild-type transporter, while the activity of R432C was reduced by at least 2 orders of magnitude. Conservative replacement of R432 with Lys reduced the activity by 1 order of magnitude, by lowering the affinity for the substrate 10-fold. It is concluded that the arginine residue at position 432 in CimH interacts with one of the carboxylate groups of the substrates. Labeling of the R420C and Q428C mutants with thiol reagents inhibited citrate transport activity. Surprisingly, the cysteine residues in the cytoplasmic loops in both R420C and Q428C were accessible to the small, membrane-impermeable, negatively charged MTSES reagent from the external site of the membrane in a substrate protectable manner. The membrane impermeable reagents MTSET, which is positively charged, and AMdiS, which is negatively charged like MTSES but more bulky, did not inhibit R420C and Q428C. It is suggested that the access pathway is optimized for small, negatively charged substrates. Either the cytoplasmic loop containing residues R420 and Q428 is partly protruding to the outside, possibly in a reentrant loop like structure, or alternatively, a water-filled substrate translocation pathway extents to the cytoplasm-membrane interface.

Sol–gel synthesis and thermal behavior of bioactive ferrous citrate–silica hybrid materials

Imbalance of the iron level in the body causes several diseases. In particular, the low level of iron, during pregnancy, is responsible for the iron deficiency anemia, and even of neurodegenerative diseases. Although the treatment of iron deficiency anemia with oral iron supplements has been known, this problem still afflicts many people. The aim of this work was the development of a system able to release ferrous ions in a controlled manner. Controlled drug release for medical applications, indeed, appears to be a very interesting alternative to a systemic therapy because it is assurance of treatment continuity and drug stability and optimizes drug absorption. For this purpose, ferrous citrate (Fe(II)C) was synthesized by a redox reaction between iron powder and citric acid. Fourier transform infrared spectroscopy (FTIR), 1,10-phenanthroline and sodium thiocyanate colorimetric assays confirmed that only Fe(II)C was obtained by redox reaction. Afterward, obtained Fe(II)C was embedded within a SiO2 matrix in different mass percentage, by means of a sol–gel route. FTIR spectroscopy and simultaneous thermogravimetry/first-order derivative of thermogravimetry were used to confirm the Fe(II)C presence in the silica matrix and to investigate the thermal behavior of the sol–gel materials, respectively. The bioactivity test carried out by soaking the synthesized drug delivery systems in a simulated body fluid showed that the biological properties of the silica matrix are not modified by the presence of Fe(II)C

Nanosized LaCo0.6Fe0.4O3 perovskites synthesized by citrate sol gel auto combustion method

LaCo0.6 Fe0.4 O3 (LCFO) nanopowder was synthesized from constituent metal nitrates, citric acid and ethylene glycol by citrate sol gel autocombustion method and calcined at different temperatures. The powders were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive X-ray analysis (EDAX) and Fourier transform infrared spectra (FTIR), whereas dielectric properties were investigated with LCR-meter. The FTIR spectra, taken for the xerogel and the sample calcined at 1000 °C, confirm that the organic groups were removed during calcination and oxide structure was formed. The XRD result shows that LCFO has rhombhohedral crystal structure with R-3C space group and forms single phase after calcination at 600 °C. The activation energy of crystallite growth, determined from the Arrhenius plot, was 17±2 kJ/mol. Surface feature studies of the powders were obtained from SEM. At 1000 °C, dense microstructure with well-shaped grain boundaries was obtained and the average grain size was around 400 nm. EDAX confirms the elemental composition. Finally, from the dielectric studies, it was found that the dielectric constant (εr ) as well as dielectric loss tangent (tan δ) decreases with increase in frequency

Effect of synthetic route on sintering behaviour, phase purity and conductivity of Sr- and Mg-doped LaGaO3 perovskites

La1-xSrxGa1-yMgyO3-d (LSGM) powders containing different amounts of Sr2+ and Mg2+ were prepared from precursors synthesised by either Pechini or citrate sol-gel method and by subsequent calcination at 1400 °C. Some powders were also submitted to further 10 h firing at 1500 °C. All as-calcined powders contained small amounts of Sr- and Ga-containing phases (namely SrLaGa3O7 and SrLaGaO4), as detected by X-Ray Diffraction (XRD). The relative amounts of these phases depended on x and y, i.e. the dopants’ levels. Nevertheless, powders prepared by the citrate method exhibited systematically higher phase purity than those obtained by the Pechini process. Calcined powders were then sintered at 1500 °C (10 h) in air and the degree of sintering was assessed by scanning electron microscopy (SEM). Phase composition of sintered pellets was different from that of powders. In fact, sintered pellets showed the presence of MgO, as detected by SEM, and of lesser amounts of SrLaGa3O7. Both these phases were less abundant in materials sintered using powders prepared by citrate method, thus suggesting that Pechini method does not represent the best wet chemical process for manufacturing. The conductivity of sintered pellets was measured by impedance spectroscopy in the 600–800 °C interval. Conductivity values of LSGM materials were affected by secondary phase segregation and, therefore, depended on both composition and sol-gel method synthetic route

Characterization of Shewanella oneidensis MtrC: a cell-surface decaheme cytochrome involved in respiratory electron transport to extracellular electron acceptors

MtrC is a decaheme c-type cytochrome associated with the outer cell membrane of Fe(III)-respiring species of the Shewanella genus. It is proposed to play a role in anaerobic respiration by mediating electron transfer to extracellular mineral oxides that can serve as terminal electron acceptors. The present work presents the first spectropotentiometric and voltammetric characterization of MtrC, using protein purified from Shewanella oneidensis MR-1. Potentiometric titrations, monitored by UV–vis absorption and electron paramagnetic resonance (EPR) spectroscopy, reveal that the hemes within MtrC titrate over a broad potential range spanning between approximately +100 and approximately -500 mV (vs. the standard hydrogen electrode). Across this potential window the UV–vis absorption spectra are characteristic of low-spin c-type hemes and the EPR spectra reveal broad, complex features that suggest the presence of magnetically spin-coupled low-spin c-hemes. Non-catalytic protein film voltammetry of MtrC demonstrates reversible electrochemistry over a potential window similar to that disclosed spectroscopically. The voltammetry also allows definition of kinetic properties of MtrC in direct electron exchange with a solid electrode surface and during reduction of a model Fe(III) substrate. Taken together, the data provide quantitative information on the potential domain in which MtrC can operate

Influence of calcium-binding salts on heat stability and fouling of whey protein isolate dispersions

peer-reviewedThe effect of the calcium-binding salts (CBS), trisodium citrate (TSC), tripotassium citrate (TPC) and disodium hydrogen phosphate (DSHP) at concentrations of 1–45 mm on the heat stability and fouling of whey protein isolate (WPI) dispersions (3%, w/v, protein) was investigated. The WPI dispersions were assessed for heat stability in an oil bath at 95 °C for 30 min, viscosity changes during simulated high-temperature short-time (HTST) and fouling behaviour using a lab-scale fouling rig. Adding CBS at levels of 5–30 mm for TSC and TPC and 25–35 mm for DSHP improved thermal stability of WPI dispersions by decreasing the ionic calcium (Ca2+) concentration; however, lower or higher concentrations destabilised the systems on heating. Adding CBS improved heat transfer during thermal processing, and resulted in lower viscosity and fouling. This study demonstrates that adding CBS is an effective means of increasing WPI protein stability during HTST thermal processing

Methane dry reforming over nickel perovsikite catalysts

In recent years dry reforming of methane (DRM) has received considerable attention as a promising alternative to steam reforming for synthesis gas (H2 and CO) production. This process could be industrially advantageous, yielding a syngas with a H2/CO ratio close to 1, suitable for Fischer-Tropsch synthesis to liquid hydrocarbons and for production of valuable oxygenated chemicals. The major drawback of the process is the endothermicity of the reaction that implies the use of a suitable catalyst to work at relatively low temperatures (923-1,023 K). Higher temperatures would make the process unaffordable for an industrial development and would increase the risk of undesirable side reactions, such as coke formation, that are the main causes of catalyst deactivation. In this work the activity of nickel perovskite catalysts were studied and the results were compared with rhodium perovskite. It is well known that rhodium is very active and stable for dry reforming but its high cost makes its utilization limited. The Ni, due to its low cost, is a promising substitute even if it is more susceptible to coking. The perovskite structure allows a high dispersion of the metal into the catalyst increasing the catalytic activity. In this work the Ni perovskite was obtained with two methods (auto-combustion and modified citrate methods). The results pointed out that the Ni perovskite obtained with the auto-combustion method is a promising route for the use of Ni in this process. The experimental tests show that with Ni catalyst very good activity can be achieved from temperature of 973 K

The effects of bicarbonate and mineral surfaces on uranium immobilization under anaerobic conditions

For four decades, from 1940 through 1980, the U.S. Department of Energy (DoE) extensively mined and processed uranium at various sites. As a result, widespread uranium contamination exists in subsurface sediments and aquifers. In subsurface environments, uranium primarily exists as U(VI) or U(IV), oxidized and reduced species, respectively. U(VI) is highly soluble and toxic, U(IV), while relatively toxic, is insoluble which greatly reduces its exposure pathways. We seek to examine the role of ferric iron on U(VI) reduction by adsorbing U(VI) onto ferric and non-ferric mineral surfaces in the presence of a reductant. Further, we seek to understand the role that NaHCO3, a natural groundwater buffer, has in the reductive geochemical transformations of U(VI) adsorbed on ferric and non-ferric mineral surfaces. Bench top studies were performed using 100 uM U(VI) and the reductant AHQDS, in the presence and absence of Fe-Gel (amorphous ferric oxyhydroxide) and gamma-Al2O3. In the presence of a HEPES buffer at pH 8, results demonstrate direct homogeneous reduction in several hours in the absence of Fe-Gel or gamma-Al2O3, and reduction within a 48-hour period in the presence Fe-Gel or gamma-Al2O3. While adsorbed to both ferric and non-ferric mineral surfaces, U(VI) reduction is inhibited. U(VI) reduction in the presence of NaHCO3 buffer also inhibits U(VI) reduction