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PubMed2002

Tumour cell uptake of the metastasis inhibitor ruthenium complex NAMI-A and its in vitro effects on KB cells.

PURPOSE: The uptake of NAMI-A (imidazolium trans-imidazoledimethylsulphoxidetetrachlororuthenate) by KB cells in vitro was compared with the effects of this compound on the cell cycle phase distribution of the cells. METHODS: NAMI-A uptake was determined by flameless atomic absorption spectroscopy, and the cell cycle phase distribution was determined by flow cytometry. RESULTS: NAMI-A uptake was proportional to its concentration in the incubation medium. The use of a number of incubation conditions showed that NAMI-A uptake from MEM was independent of the presence of serum and dependent on the presence of amino acids in the incubation medium, and that NAMI-A uptake was markedly higher when the cells were incubated in PBS. The uptake increase observed in PBS did not occur when the cells were kept at 0-4 degrees C, suggesting the presence of active transportation of NAMI-A into cells. In addition, the presence of divalent cations such as Ca(2+) and Mg(2+), appeared to facilitate NAMI-A uptake. The anionic substance transport inhibitor probenecid significantly reduced the active transportation of NAMI-A into cells. The effects of NAMI-A on cell cycle distribution were strictly dependent on its uptake by tumour cells and not on its extracellular concentration. CONCLUSIONS: These findings suggest the interaction of NAMI-A with biological components resulting in possible consequences for the distribution of the compound itself. Furthermore, NAMI-A enters tumour cells both by passive diffusion and by active transportation.

Amino Acids↗
PubMed1994

The effect of sweeteners on bitter taste in young and elderly subjects.

The purpose of this study was to quantify the degree of reduction in perceived bitterness by sweeteners at both threshold and suprathreshold concentrations of bitter compounds. Detection and recognition thresholds were determined for six bitter compounds (caffeine, denatonium benzoate, magnesium chloride, quinine hydrochloride, sucrose octaacetate, and urea) in the absence and presence of several suprathreshold concentrations of five sweeteners. The sweeteners were: sucrose, aspartame, sodium saccharin, mannitol, and sorbitol. Polycose was also tested along with the sweeteners. The degree to which bitter thresholds were affected by the addition of sweeteners was dependent on the chemical classification of the sweeteners and their concentrations. In general, the natural sweeteners, sucrose, mannitol, and sorbitol, were more effective than the noncaloric sweeteners, aspartame and sodium saccharin, in elevating the detection and recognition thresholds of the bitter compounds. A sweetness intensity approximating that of 6% sucrose (0.175 M sucrose) or greater was required to elevate thresholds. For elderly subjects, sweeteners did not significantly elevate thresholds for denatonium benzoate and sucrose octaacetate. The degree to which sorbitol and sucrose can decrease the perceived bitterness intensity of suprathreshold concentrations of the six bitter compounds was also determined. The concentrations of sweeteners and bitter compounds were selected to be of moderate to high subjective intensity. The levels of sweeteners used in the mixtures were: sucrose (none, 0.946 M, and 2.13 M) and sorbitol (none, 2.1 M, and 3.68 M). Both sweeteners significantly reduced the bitterness ratings of almost every concentration of the six bitter compounds. The greatest reductions in bitterness were 87.0% for 0.192 microM denatonium benzoate mixed with 2.13 M sucrose and 84.7% for 1.8 M urea mixed with 3.68 M sorbitol.

Adult↗
PubMed2006

Solutions to a combined problem of excessive hydrogen sulfide in biogas and struvite scaling.

The Woodman Point Wastewater Treatment Plant (WWTP) in Western Australia has experienced two separate problems causing avoidable maintenance costs: the build-up of massive struvite (MgNH4PO4. 6H2O) scaling downstream of the anaerobic digester and the formation of hydrogen sulfide (H2S) levels in the digester gas to levels that compromised gas engine operation and caused high operating costs on the gas scrubber. As both problems hang together with a chemical imbalance in the anaerobic digester, we decided to investigate whether both problems could be (feasibly and economically) addressed by a common solution (such as dosing of iron solutions to precipitate both sulfide and phosphate), or by using separate approaches. Laboratory results showed that, the hydrogen sulfide emission in digesters could be effectively and economically controlled by the addition of iron dosing. Slightly higher than the theoretical value of 1.5 mol of FeCl3 was required to precipitate 1 mol of dissolved sulfide inside the digester. Due to the high concentration of PO4(3-) in the digested sludge liquor, significantly higher iron is required for struvite precipitation. Iron dosing did not appear an economic solution for struvite control via iron phosphate formation. By taking advantage of the natural tendency of struvite formation in the digester liquid, it is possible to reduce the risk of struvite precipitation in and around the sludge-dewatering centrifuge by increasing the pH to precipitate struvite out before passing through the centrifuge. However, as the Mg2+/PO4(3-) molar ratio in digested sludge was low, by increasing the pH alone (using NaOH) the precipitation of PO4(3-) was limited by the amount of cations (Ca2+ and Mg2+) available in the sludge. Although this would reduce struvite precipitation in the centrifuge, it could not significantly reduce PO4(3-) recycling back to the plant. For long-term operation, maximum PO4(3-) reduction should be the ultimate aim to minimise PO4(3-) accumulation in the plant. Magnesium hydroxide liquid (MHL) was found to be the most cost-effective chemical to achieve this goal. It enhanced struvite precipitation from both, digested sludge and centrate to the point where more than 95% PO4(3-) reduction in the digested sludge was achieved.

Bacteria, Anaerobic↗
PubMed1994

Coaxially stacked RNA helices in the catalytic center of the Tetrahymena ribozyme.

Coaxial stacking of helical elements is a determinant of three-dimensional structure in RNA. In the catalytic center of the Tetrahymena group I intron, helices P4 and P6 are part of a tertiary structural domain that folds independently of the remainder of the intron. When P4 and P6 were fused with a phosphodiester linkage, the resulting RNA retained the detailed tertiary interactions characteristic of the native P4-P6 domain and even required lower magnesium ion concentrations for folding. These results indicate that P4 and P6 are coaxial in the P4-P6 domain and, therefore, in the native ribozyme. Helix fusion could provide a general method for identifying pairs of coaxially stacked helices in biological RNA molecules.

Animals↗
PubMed2002

MgF(3)(-) as a transition state analog of phosphoryl transfer.

The formation of complexes between small G proteins and certain of their effectors can be facilitated by aluminum fluorides. Solution studies suggest that magnesium may be able to replace aluminum in such complexes. We have determined the crystal structure of RhoA.GDP bound to RhoGAP in the presence of Mg(2+) and F(-) but without Al(3+). The metallofluoride adopts a trigonal planar arrangement instead of the square planar structure of AlF(4)(-). We have confirmed that these crystals contain magnesium and not aluminum by proton-induced X-ray emission spectroscopy. The structure adopted by GDP.MgF(-) possesses the stereochemistry and approximate charge expected for the transition state. We suggest that MgF3(-) may be the reagent of choice for studying phosphoryl transfer reactions.

Aluminum Compounds↗
PubMed1975

Constituents of urinary calculi containing struvite.

In a collection of 615 stones containing struvite and in which the sequential deposition of the constituents from the nucleus to the surface had been determined, other substances were found to follow a marked deposition of struvite in 139 cases. In 122, the compound was accompanied by struvite, in 16, struvite was replaced by it and in 1, both types of deposition had occurred in different layers. All urinary stone constituents could accompany struvite and many could replace this compound.

Humans↗
PubMed1989

Nutritional availability of magnesium and calcium in magnesium-supplemented diets.

The nutritive utilization of magnesium and calcium was studied using two different formulations of Mg: MgCO3 and an organic dietary Mg preparation. The influence of supplementation with the latter was also studied. The dietary organic magnesium did not modify food intake, which remained adequate in all animals used in the present experiments. Magnesium in both inorganic compound and organic preparation form was well absorbed; furthermore, absorption levels of the latter remained quite stable throughout the different experimental periods. Mg balance in both muscle and femur was similar in all groups studied. Digestive utilization of Ca and Ca content in the longissimus dorsi were higher in animals fed the organic Mg preparation while Ca levels in blood and femur were not affected.

Animals↗
PubMed1997

Iron toxicity in yeast.

It has been found that yeast cells are sensitive to iron overload only when grown on glucose as a carbon source. Effective concentration of ferrous iron is much higher than that found in natural environments. Effects of ferrous iron are strictly oxygen dependent, what suggest that the formation of hydroxyl radicals in the Fenton reaction is a cause of the toxicity. Respiratory deficiency and pretreatment of cells with antimycin A prevent toxic effects in the late exponential phase of growth, whereas uncouplers and 2mM magnesium salts completely protect even the most vulnerable exponential cells. Generally, toxic effects correlate with the ability of cells to take up this metal. The results presented suggest that during ferrous iron overload iron is transported through the unspecific divalent cation uptake system which is known in fungi. The data suggest that recently described high and low affinity systems of iron uptake in yeast are the only source of iron in natural environments.

Antimycin A↗
PubMed1982

Multiple compression of powders in a tablet press.

Lactose, magnesium carbonate, phenacetin, microcrystalline cellulose and directly compressible starch compacts were repeatedly compressed in a tablet press, the tablets not being ejected from the die between compressions. When the interval between compressions was 1.3 s, all substances showed a decrease in the maximum force exerted by the tablet press, this being attributed to the formation of a structure of lower porosity. As the intervals between compressions is increased, the decrease in force is reduced, and in the case of microcrystalline cellulose and directly compressible starch, the force exerted at the second compression is greater than that exerted by the first.

Carbonates↗
PubMed1986

Modulation of activity of human alkaline phosphatases by Mg2+ and thiol compounds.

Interaction of purified human liver and placental alkaline phosphatases (orthophosphoric-monoester phosphohydrolase (alkaline optimum), EC 3.1.3.1) with sulfhydryl groups, sulfhydryl reagents, and Mg2+ were studied. L-Cysteine (0.1 mmol/l) or Mg2+ activated the liver enzyme 4-5-fold and the placental enzyme 2-3-fold, with optimal pH 7.5-8.0; these activations were not additive. L-Cysteine (2 mmol/l) inhibited both enzymes maximally at pH greater than 9.0; phosphate protected the enzymes. S-Methylcysteine had little effect, with or without Mg2+. Inhibition by sulfur-containing compounds paralleled their ability to bind Zn2+. Fluoresceine mercury acetate (specific for sulfhydryl groups) inhibited the isoenzymes, whereas iodoacetic acid, iodoacetamide, dithionitrobenzoic acid, and p-chloromercuribenzoate had little effect. The inhibition was reversed by L-cysteine and only slightly protected by inorganic phosphate. Thus, there are two sites on human liver and placental alkaline phosphatase that interact with L-cysteine; a Mg2+-binding site, which results in activation, and a site that involves one or both of the bound Zn2+ ions and results in inactivation. Both enzymes have a protected essential thiol group.

Alkaline Phosphatase↗
PubMed2000

Syntheses, structures, and reactivities of heteroleptic magnesium amide thiolates.

The syntheses and characterizations of a family of novel heteroleptic magnesium amide thiolates are presented. The compounds are synthesized by ligand redistribution chemistry involving reactions of equimolar amounts of magnesium amides and magnesium thiolates. Utilization of the smaller thiolates [Mg(SPh)2]n and [Mg(S-2,4,6-iPr3C6H2)2]n results in the isolation of dimeric species, [Mg(THF)(N(SiMe3)2)(mu-SR)]2 (R = Ph (1), 2,4,6-iPr3C6H2 (2)), with four-coordinate metal centers and bridging thiolate functions. The sterically more encumbered thiolate S-2,4,6-tBu3C6H2 induces the formation of the four-coordinate, monomeric species Mg(THF)2(N(SiMe3)2)(S-2,4,6-tBu3C6H2) (3)). Careful choice of reaction conditions allows the successful syntheses of pure heteroleptic compounds; however, it remains difficult to obtain the compounds in high yields, since a tendency toward product symmetrization and ligand redistribution under re-formation of the starting materials is prevalent. One of these symmetrized products is also included in this report: the dimeric, four-coordinate magnesium thiolate [Mg-(THF)(S-2,4,6-tBu3C6H2)(mu-S-2,4,6-tBu3C6H2)]2 (4), isolated as the product of the reaction between [Mg-(N(SiMe3)2)2]2 and Mg(THF)2(S-2,4,6-tBu3C6H2)2. All compounds were characterized by NMR and IR spectroscopy, elemental analyses, and X-ray crystallography. Crystal data obtained with Mo K alpha (lambda = 0.710 73 A) radiation are as follows. 1: C16H31MgNOSSi2, a = 11.2100(1) A, b = 17.4512(3) A, c = 11.2999(2) A, beta = 97.952(1) degrees, V = 2189.32(6) A3, Z = 4, monoclinic, space group P2(1)/n, R1 (all data) = 0.0934. 2: C25H49MgNOSSi2, a = 11.1691(1) A, b = 11.0578(1) A, c = 26.0671(4) A, beta = 99.906(1) degrees, V = 3171.44(6) A3, Z = 4, monoclinic, space group P2(1)/c, R1 (all data) = 0.0557. 3: C36H71MgNO3SSi2, a = 42.8293(16) A, b = 10.9737(5) A, c = 16.8305(7) A, beta = 98.755(3) degrees, V = 7818.1(6) A3, Z = 8, monoclinic, space group C2/c, R1 (all data) = 0.1331. 4: C80H132Mg2O2S4, a = 18.8806(2) A, b = 19.3850(2) A, c = 27.3012(4) A, beta = 97.250(1) degrees, V = 9912.4(2) A3, Z = 4, monoclinic, space group P2(1)/n, R1 (all data) = 0.1023.

Journal Article↗
PubMed1999

The hepatitis C virus internal ribosome entry site adopts an ion-dependent tertiary fold.

Hepatitis C virus (HCV) contains an internal ribosome entry site (IRES) located in the 5' untranslated region of the genomic RNA that drives cap-independent initiation of translation of the viral message. The approximate secondary structure and minimum functional length of the HCV IRES are known, and extensive mutagenesis has established that nearly all secondary structural domains are critical for activity. However, the presence of an IRES RNA tertiary fold and its functional relevance have not been established. Using chemical and enzymatic probes of the HCV IRES RNA in solution, we show that the IRES adopts a unique three-dimensional structure at physiological salt concentrations in the absence of additional cofactors or the translation apparatus. Folding of the IRES involves cooperative uptake of magnesium and is driven primarily by charge neutralization. This tertiary structure contains at least two independently folded regions which closely correspond to putative binding sites for the 40 S ribosomal subunit and initiation factor 3 (eIF3). Point mutations that inhibit IRES folding also inhibit its function, suggesting that the IRES tertiary structure is essential for translation initiation activity. Chemical and enzymatic probing data and small-angle X-ray scattering (SAXS) experiments in solution show that upon folding, the IRES forms an extended structure in which functionally important loops are exposed. These results suggest that the 40 S ribosomal subunit and eIF3 bind an HCV IRES that is prefolded to spatially organize recognition domains.

Base Sequence↗
PubMed1993

Theoretical analyses on the role of metal cations in RNA cleavage processes.

Previously, we found that locations of metal cations in biomolecules, such as proteins and nucleotides, were in accord with predictions based on electrostatic-potential calculations of the nearest polar functional groups. Electrostatic potential of a cyclic oxyphosphorane dianion 2, which is a model compound for an intermediate or a transition state for the hammerhead ribozyme reaction, indicates that Mg2+ coordinations at the regions between axial (bridging) and equatorial (phosphoryl) oxygens are most favorable. If we consider the fact that negative charge is concentrated on two of the equatorial phosphoryl oxygens in the transition state 2, the axial-equatorial coordination is an unexpected result. Nevertheless, experimental results also support such an axial-equatorial coordination. Therefore, hammerhead ribozyme is a metalloenzyme in which at least one Mg2+ ion acts as a base and possibly a second Mg2+ ion acts as a Lewis acid. The double Mg2+ ion catalysis may be a common mechanism among various types of ribozyme and some protein enzymes as well.

Animals↗
PubMed2004

Uptake of iron by a vegetable; kaiware daikon (Japanese radish sprout).

Uptake of iron and several other minerals into kaiware daikon (Japanese radish sprout) was investigated by changing their supplementary conditions. The supplementation of calcium sulfate (0.1% (w/v), 230 ppm as calcium ion) and iron (III) chloride (0.1% (w/v), 200 ppm as iron ion) in hydroponics promoted the growth of kaiware daikon ca. 1.0-1.5 cm longer than the control group of no additions, while magnesium sulfate (0.1% (w/ v), 100 ppm as magnesium ion) did not affect the length of sprouts so much, but caused their leaves to grow a little wider. Mineral contents in the sprout were maximal when it was added, at ca. 0.1% (w/v), to the hydroponic solution. In tests regarding iron (II) ion supplementation, the color of the kaiware daikon seeds changed from brownish to black and the sprout did not grow well. In contrast, the iron (III) ion did not affect their color and promoted growth of the sprout. When the seeds were soaked in an iron (II) sulfate (75 ppm) or an ammonium iron (III) citrate (180 ppm) solution for 24 h prior to germination, the resulting kaiware daikon contained a few times higher the amount of iron than commercially available ones.

Absorption↗
PubMed2002

Optimal conditions for bio-oxidation of ferrous ions to ferric ions using Thiobacillus ferrooxidans.

A chemo-biochemical process using Thiobacillus ferrooxidans for desulphurization of gaseous fuels and emissions containing hydrogen sulphide (H2S) has been developed. In the first stage, H2S present in fuel gas and emissions is selectively oxidized to elemental sulphur using ferric sulphate. The ferrous sulphate produced in the first stage of the process is oxidized to ferric sulphate using Thiobacillus ferrooxidans for recycle and reuse in the process. The effects of process variables, temperature, pH, total dissolved solids (TDS), elemental sulphur, ferric and magnesium ions on bio-oxidation of ferrous ions to ferric ions were investigated using flask culture experiments. The bio-oxidation of ferrous ions to ferric ions could be achieved efficiently in the temperature range of 20(+/-1)-44(+/-1) degrees C. A pH range of 1.8(+/-0.02)-2.2(+/-0.02) was optimum for the growth of culture and effective bio-oxidation of ferrous ions to ferric ions. The effect of TDS on bio-oxidation of ferrous ions indicated that a preacclimatized culture in a growth medium containing high dissolved solid was required to achieve effective bio-oxidation of ferrous ions. Elemental sulphur ranging from 1000 to 100,000 mg/l did not have any effect on efficiency of ferrous ion oxidation. The efficiency of bio-oxidation of ferrous ions to ferric ions was not affected in the presence of ferric ions up to a concentration of 500 mg/l while 3 mg/l of magnesium ion was optimal for achieving effective bio-oxidation.

Bioreactors↗
PubMed1991

Influence of oral co-administered metallic drugs on ofloxacin pharmacokinetics.

Following recent concern over probable interactions between the 4-quinolones and metal ions, the effect of co-administered drugs--sodium bicarbonate, potassium citrate, ferrous sulphate, magnesium trisilicate, calcium carbonate and aluminium hydroxide--on the saliva and urine pharmacokinetics of ofloxacin in healthy human volunteers has been investigated. The Cmax and AUC0-9 in saliva were generally in the range 1.05-1.40 mg/L and 4.89-6.16 mg.h/L, respectively, and were unaffected (P less than 0.05) by the metallic drugs, except aluminium hydroxide which lowered these values. Again, only aluminium hydroxide modified the Ka of ofloxacin, resulting in a slower absorption rate. However, none of the metallic drugs altered the T1/2 beta of the 4-quinolone in saliva. In-vitro studies using simulated gastric fluid showed that ferrous sulphate, aluminium hydroxide and calcium carbonate reduced ofloxacin availability to 67.4%, 69.3% and 73.8%, respectively. This effect was ascribed to the formation of complexes between ofloxacin and the metal ions concerned. Substantial correlation between in-vitro and in-vivo availability data was demonstrated in all cases except for ofloxacin combinations with ferrous sulphate and calcium carbonate. In general, there was also good correlation between the saliva and urine data.

Adult↗
PubMed1994

[Study of neuromuscular transmission with evoked electromyography--11. Comparison between blocks by magnesium and by pancuronium].

Effects of magnesium (Mg) on muscle compound action potentials (CAPs) which were elicited from gastrocunemius muscle by sciatic nerve stimulation in cats were studied, and the results were compared with those of alpha-bungarotoxin (alpha BuTX) and of non-depolarizing relaxants which had been reported previously. Recovery curves (RCs) of CAPs and train-of-four ratios (TOFR) as parameters of neuromuscular blockade were estimated during blocks by Mg as well as the methods described in the previous reports. The following results were obtained. 1) Neuromuscular blocks which were dependent on serum [Mg2+] were observed in accordance with cumulative dosages of MgSO4 solutions. 2) Recovery curves of CAPs showed a pattern which was characterized by extreme potentiations of test responses at shorter intervals of paired stimuli, followed by a slight depression at longer intervals than 500 msec. This pattern of RC was remarkably different from those after alpha BuTX and relaxants. 3) The mechanisms to produce these differences of RCs were discussed, and it is concluded that the notable depression of RCs derived from muscle relaxants may be caused by inhibitory effect on nerve terminals of relaxants which have different mechanism from that by Mg.

Animals↗