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Magnesium-sugar interaction. Synthesis, spectroscopic and structural characterization of Mg-sugar complexes containing beta-D-fructose.

The interaction between beta-D-fructose and hydrated magnesium salts has been studied and complexes of the type Mg(beta-D-fructose)Cl2.4H2O and Mg(beta-D-fructose)Br2.4H2O have been isolated and characterized. On the basis of comparisons of the spectroscopic and other chemical properties of several structurally known calcium-fructose compounds with those of the corresponding magnesium complexes, it is concluded that Mg2+ binds to two sugar moieties via O(2), O(3) of the first and O(4), O(5) of the second and to two water molecules, resulting in a six-coordinate geometry around the Mg2+. The strong sugar hydrogen-bonding network is rearranged upon sugar metallation and the sugar moiety shows the beta-anomer conformation in these magnesium-sugar complexes.

Journal Article↗

Calcium and thiol reactivity of human plasma clotting factor XIII.

1. The reaction of iodoacetate, 2-chloromercuri-4-nitrophenol and 5,5'-dithiobis-(2-nitrobenzoate) with thrombin-cleaved Factor XIII (i.e. Factor XIII(a)) was accompanied by enzyme inhibition. 2. The reaction with iodoacetate and 5,5'-dithiobis-(2-nitrobenzoate) was absolutely dependent on Ca(2+), and the rate of reaction increased with the Ca(2+) concentration up to very high, non-physiological concentrations. 3. 2-Chloromercuri-4-nitrophenol reacted with Factor XIII(a) in the absence of Ca(2+), but at a much slower rate. 4. Stopped-flow methods were used to quantify the reaction with 5,5'-dithiobis-(2-nitro-benzoate) because of the Ca(2+)-dependent dissociation of Factor XIII(a) (a'(2)b(2)) and subsequent aggregation of the a' chains into turbid precipitates. 5. The 3-carboxy-4-nitrothio-phenolate released was consistent with the reaction of 2 thiol groups/molecule of Factor XIII(a). The isolated b chains of Factor XIII did not react with either of the chromophoric reagents. This indicated that the a' chains of Factor XIII(a) were responsible for the thiol reactivity of the enzyme. 6. The Ca(2+) dependence of the enzyme inhibition by these thiol reagents was very dependent on protein concentration. This is discussed in relation to the Ca(2+)-induced dissociation of Factor XIII(a). 7. The acceptor substrate, casein, decreased the Ca(2+) concentration required for enzyme inhibition by both the mercurial and the aromatic disulphide compounds. Dansylcadaverine did not affect Ca(2+) dependence of inhibition.

Cadaverine↗

Modulation of electrolyte excretion by potassium retaining diuretics.

Triamterene and amiloride belong to the potassium retaining diuretics of the cycloamidine type. These agents exert natriuretic as well as antikaliuretic effects. After administration of high doses an additional magnesium-sparing property also becomes evident. Whereas amiloride is only metabolized to a minor extent, triamterene is rapidly bio-transformed to the phase-I metabolite, hydroxytriamterene, and the phase-II metabolite, hydroxytriamterene sulphuric acid ester. This acidic phase-II metabolite is still diuretically active, but its electrolyte excretion profile is different from the parent compound: although the natriuretic properties are not altered, the potassium retention is very weak. Further studies in rats with cycloamidine derivatives of the triamterene type containing neutral, acidic or basic side chains at the phenyl moiety as well as with basic pteridine derivatives, revealed further evidence that the natriuretic, antikaliuretic and antimagnesiuretic effects can be influenced almost independently by structural variations of the parent drug. Thus, it was possible to obtain compounds predominantly increasing sodium excretion without affecting potassium or magnesium excretion. On the other hand, substances could be developed with mainly antikaliuretic effects, or compounds, which enhanced sodium and reduced magnesium excretion and did not interfere with the potassium elimination. Based on these findings, it can be concluded that distal tubular transport of sodium, potassium and magnesium may be influenced independently from each other. These renal effects of triamterene and its derivatives seem to be independent of their antiarrhythmic actions, as suggested by recent studies.

Animals↗

Overexpression, purification and characterization of Dictyostelium calcineurin A.

The catalytic subunit of Ca2+/calmodulin-dependent protein phosphatase (calcineurin A) was overexpressed about 50-fold in Dictyostelium discoideum cells transformed with a vector containing the cDNA for D. discoideum calcineurin A under control of the actin-6 promoter. In crude lysates from the overexpressing cell line, high Ca2+/calmodulin-stimulated phosphatase activity was detected. Calcineurin A was purified by anion exchange chromatography and calmodulin-Sepharose affinity chromatography, and the enzymatic activity of the isolated protein was characterized. Its phosphatase activity was strictly dependent on the addition of divalent metal ions such as Mg2+ or Mn2+. Disulphide-reducing agents increased the activity more than 10-fold. Ca2+/calmodulin stimulated the activity by a factor of 2.5-5. Despite the high extra Ca2+/calmodulin-dependent phosphatase activity, the overexpressing cell line showed no phenotypic aberrations.

Aniline Compounds↗

Recent advances in ceramics for dentistry.

For the last ten years, the application of high-technology processes to dental ceramics allowed for the development of new materials such as heat-pressed, injection-molded, and slip-cast ceramics and glass-ceramics. The purpose of the present paper is to review advances in new materials and processes available for making all-ceramic dental restorations. Concepts on the structure and strengthening mechanisms of dental ceramics are provided. Major developments in materials for all-ceramic restorations are addressed. These advances include improved processing techniques and greater mechanical properties. An overview of the processing techniques available for all-ceramic materials is given, including sintering, casting, machining, slip-casting, and heat-pressing. The most recent ceramic materials are reviewed with respect to their principal crystalline phases, including leucite, alumina, forsterite, zirconia, mica, hydroxyapatite, lithium disilicate, sanidine, and spinel. Finally, a summary of flexural strength data available for all-ceramic materials is included.

Aluminum Compounds↗

A novel additive for the reduction of acid gases and NO(x) in municipal waste incinerator flue gas.

The reduction of SO2, HCl, and NO(x) concentrations using calcium magnesium acetate (CMA) as a novel sorbent in a simulated municipal waste incinerator flue gas was investigated. The reduction of individual SO2, HCl, and NO(x) concentrations was tested at 850 degrees C and it was found that CMA could reduce the SO2 concentration by 74%, HCl concentration by 64%, or NO(x) concentration by 94%. It was observed that individual SO2 or HCl capture increased with increasing initial oxygen concentration in the reacting gas or increasing sorbent input. NO(x) reduction decreased with increasing initial oxygen concentration in the reacting gas. The simultaneous reduction of SO2, HCl, and NO(x) concentrations by CMA was also investigated. It was found that CMA could simultaneously capture 60% SO2 and 61% HCl and reduce NO(x) concentrations by 26%, when the initial oxygen concentration in the reacting gas was 4%. During the simultaneous reduction of SO2, HCl, and NO(x), it was noted that as the initial oxygen concentration in the reacting gas increased, the efficiency of SO2 capture increased too, but the efficiency of HCl capture and the efficiency of NO(x) destruction decreased.

Acetates↗

Modulation of crystalline Proteus mirabilis biofilm development on urinary catheters.

The crystalline biofilms formed by Proteus mirabilis can seriously complicate the care of patients undergoing long-term bladder catheterization. The generation of alkaline urine by the bacterial urease causes calcium and magnesium phosphates to precipitate from urine and accumulate in the catheter biofilm, blocking the flow of urine from the bladder. The pH at which these salts crystallize from a urine sample, the nucleation pH (pH(n)), can be elevated by diluting the urine and by increasing its citrate content. The aim of this study was to examine whether manipulation of pH(n) in these ways modulated the rate at which crystalline biofilm developed. Experiments in laboratory models of the catheterized bladder infected with P. mirabilis showed that when the bladder was supplied with a concentrated urine (pH(n) 6.7) at a low fluid output (720 ml per 24 h), catheters blocked at 19-31 h. Diluting this urine 1:4 increased the pH(n) to 7.5 and models supplied with this urine at 2880 ml per 24 h took 110-137 h to block. When models were supplied with urine containing citrate at 1.5 mg ml(-1) or above (pH(n) 8.3-9.1), the catheters drained freely for the full 7 day experimental period. Scanning electron microscopy revealed that the catheter biofilms that developed in urine with high pH(n) values were devoid of crystalline formations. These observations should encourage a clinical trial to examine the effect of increasing a patient's fluid intake with citrate-containing drinks on the encrustation and blockage of catheters.

Biofilms↗

Neuroprotective and cognition-enhancing properties of MK-801 flexible analogs. Structure-activity relationships.

Neuroprotective and biobehavioral properties of a series of novel open chain MK-801 analogs, as well as their structure-activity relationships have been investigated. Three groups of compounds were synthesized: monobenzylamino, benzhydrylamino, and dibenzylamino (DBA) analogs of MK-801. It was revealed that DBA analogs exhibit pronounced glutamate-induced calcium uptake blocking properties and anti-NMDA activity. The hit compound of DBA series, NT-1505, was investigated for its ability to improve cognition functions in animal model of Alzheimer's disease type dementia, simulated by treating animals with cholinotoxin AF64A. The results from an active avoidance test and a Morris water maze test showed that experimental animals, treated additionally with NT-1505, exhibited much better learning ability and memory than the control group (AF64A treated) and close to that of the vehicle group of animals (treated with physiological solution). Study of NT-1505 influence on locomotor activity revealed that it is characterized by a spectrum of behavioral activity radically different from that of MK-801, and in contrast to the latter one does not produce any psychotomimetic side effects in the therapeutically significant dose interval. The computed docking of MK-801 and its flexible analogs on the NMDA receptor elucidated the crucial role of the hydrogen bond formed between these compounds and the asparagine residue for magnesium binding in the NMDA receptor. It was suggested that strong hydrophobic interaction between MK-801 and the hydrophobic pocket in the NMDA receptor-channel complex determines much higher irreversibility of this adduct compared to the intermediates formed between this site and Mg ions or flexible DBA derivatives, which might explain the absence of PCP-like side effects of the latter compounds.

Animals↗

DNA-Protein crosslinks induced by nickel compounds in isolated rat renal cortical cells and its antagonism by specific amino acids and magnesium ion.

Suspensions of isolated renal cortical cells in modified Krebs-Henseleit buffer (pH 7.4) were incubated with nickel chloride, nickel acetate, nickel sulfate, and nickel subsulfide (0-2 mM) at 37 degreesC for 2 h. A significant increase (63%) in DNA-protein crosslinks was observed at 2 mM nickel sulfate, whereas nickel subsulfide induced a significant increase in such crosslinks beginning at 0.5 mM concentration and a maximum increase of 200% of the control value reached at 2 mM concentration. No significant reduction in viability of renal cortical cells (as measured by trypan blue exclusion) was observed due to these nickel compounds at any concentration used. In the second series of experiments, coincubation of nickel subsulfide (2 mM) with l-histidine (8 or 16 mM), l-cysteine (4 or 8 mM), or l-aspartic acid (8 or 24 mM) significantly reduced the DNA-protein crosslinks induced by 2 mM nickel subsulfide. Similarly Mg2+ (24 mM), but not Ca2+ (24 mM), was able to antagonize nickel subsulfide-induced increase in DNA-protein crosslinks. High extracellular levels of Mg2+ and these amino acids significantly decreased the accumulation of Ni2+ from nickel subsulfide in renal cortical cells. Furthermore, these amino acids at high concentrations significantly inhibited the binding of Ni2+ from nickel subsulfide to deproteinized DNA from renal cortical cells, whereas such inhibition due to Mg2+ was close to significant (0.1 > p > 0.05). In vitro exposures of renal cortical cells to nickel subsulfide (0-2 mM) increased the formation of reactive oxygen species in concentration-dependent manner. Furthermore, coincubation of 2 mM nickel subsulfide with either catalase, dimethylthiourea, mannitol, or vitamin C at 37 degreesC for 2 h resulted in a significant decrease of nickel subsulfide-induced formation of DNA-protein crosslinks, suggesting that nickel subsulfide-induced DNA-protein crosslink formation in isolated rat renal cortical cells is caused by the formation of reactive oxygen species. The potent protective effects of these specific amino acids and Mg2+ against nickel subsulfide-induced DNA-protein crosslink formation in isolated renal cortical cells are due to reduction of cellular uptake of Ni2+ and inhibition of the binding of Ni2+ to deproteinized DNA.

Amino Acids↗

Hypocalcemia and inhibition of parathyroid hormone secretion after administration of WR-2721 (a radioprotective and chemoprotective agent).

We investigated the causes of the hypocalcemia associated with WR-2721, an investigational drug that protects normal tissues against the toxic effects of radiation and chemotherapy. Sixteen patients with advanced cancers had serial measurements of serum calcium and other studies of blood chemistry before and after taking the compound. In all 16 patients (18 courses) the mean serum calcium level fell from 2.33 to 1.90 mmol per liter (9.33 to 7.62 mg per deciliter, P less than 0.001) after WR-2721, and in all 8 patients from whom data were obtained, serum calcium levels remained depressed at 24 hours. In 12 patients, ionized calcium levels dropped from 0.98 to 0.80 mmol per liter (P less than 0.01). Serum magnesium values fell from 0.96 to 0.74 mmol per liter (1.91 to 1.48 mg per deciliter, P less than 0.001). There were no changes in arterial pH or serum phosphate concentrations. In nine patients urinary calcium excretion rose from 3.96 to 10.68 mumol per minute (P less than 0.01) after WR-2721. Despite hypocalcemia, parathyroid hormone levels fell in all subjects. WR-2721 also inhibited the release of parathyroid hormone from bovine parathyroid cells incubated in vitro in low (0.5 mM) concentrations of calcium. We conclude that WR-2721 inhibits the secretion of parathyroid hormone and enhances calciuria, thereby leading to hypocalcemia.

Amifostine↗

Investigation of the Scope of Heterogeneous and Homogeneous Procedures for Preparing Magnesium Chelates of Porphyrins, Hydroporphyrins, and Phthalocyanines.

A simple method has been developed for metalation of porphyrinic compounds under homogeneous conditions at room temperature using a stable ethereal solution of MgI(2) and N,N-diisopropylethylamine. A previously developed heterogeneous procedure employs a mixture of a magnesium halide and a nonnucleophilic amine in a noncoordinating solvent at room temperature. The scope of the heterogeneous and homogeneous magnesium insertion procedures has been investigated across a family of 19 porphyrinic compounds, including synthetic porphyrins, synthetic or naturally occurring chlorins, and organic-soluble phthalocyanines. The rate of magnesium insertion increased in the series phthalocyanines < chlorins < porphyrins, which parallels the basicity of the ligands. Though phthalocyanines have the smallest core size, the magnesium phthalocyanines were far more stable than magnesium porphyrins to acid-induced demetalation. The heterogeneous method is broadly applicable to porphyrins, chlorins, and phthalocyanines. The homogeneous method is generally slower than the heterogeneous method, though both afford rapid metalation of most porphyrins, including electron-deficient, peripherally coordinating, or facially encumbered meso-substituted tetraarylporphyrins, and the beta-substituted octaethylporphyrin. Chlorin e(6) trimethyl ester and methyl pyropheophorbide a were metalated cleanly under homogeneous but not heterogeneous conditions, while pheophytin a failed with both methods. The homogeneous method failed altogether with phthalocyanines. Several methods in magnesium chemistry have been developed that augment these procedures, including a mild synthesis of tetraphenylchlorin and a streamlined separation of porphyrin, chlorin, and bacteriochlorins based on selective formation of the magnesium chelates. Collectively, these methods should broaden the scope of model systems based on magnesium chelates of porphyrinic compounds.

Journal Article↗

Use of the sodium borohydride reduction technique to identify a gamma-glutamyl phosphate intermediary in the Escherichia coli glutamine synthetase reaction.

Incubation of unadenylylated Escherichia coli glutamine synthetase with ATP, L-[14C]glutamate and metal ion results in the formation of gamma-glutamyl-P which can under appropriate conditions be reduced by sodium borohydride. The acyl-P compound is formed catalytically as judged by the quantity of radioactive alpha-amino-delta-hydroxyvalerate produced compared to the concentration of enzyme subunits. Formation of the glutamyl-P compound occurs in the presence of magnesium or manganous ions, and the relation of this apparent lack of metal ion specificity with regard to the highly specific Mg2+-supported biosynthetic activity of the unadenylylated form is discussed.

Adenosine Triphosphate↗

Simple metallic compounds as pulp-capping agents.

A study is described in which six metallic compounds identified in a previous pilot experiment were tested as pulp-capping agents using the exposed rat molar. Barium sulfate, calcium carbonate, cupric oxide, ferric oxide, and heavy magnesium oxide gave poor results. Stannic oxide gave more favorable results and is being studied further.

Animals↗