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Magnesium monoperoxophtalate: an efficient single oxygen atom donor in DNA cleavage catalyzed by metalloporphyrin.

The peracid compound magnesium monoperoxophtalate (MMPP), water-soluble at physiological pH, behaves as a promising oxygen donor in the oxidative cleavage of DNA catalyzed by meso-tetrakis-(4-N-methylpyridyl)porphyrinatomanganese(III) pentaacetate. Shown on cleavage of supercoiled phi X174 DNA, MMPP is significantly more efficient than KHSO5, another recently developed single oxygen atom donor (Fouquet et al., J. Chem. Soc., Chem. Commun., 1987, 1169).

Bacteriophage phi X 174↗

Pressure dependence of the superconducting transition temperature of magnesium diboride.

We studied the pressure and temperature dependence of the electrical resistivity of the superconducting compound magnesium diboride (MgB(2)). The superconducting transition temperature decreases monotonically with pressure, being parabolic or linear, depending on samples. The rate of decrease under pressure is higher than in conventional superconductors. We discuss our results in terms of the semimetallic character of the electronic band structure of MgB(2).

Journal Article↗

Solid-state 25Mg NMR spectroscopic and computational studies of organic compounds. square-pyramidal magnesium(II) ions in aqua(magnesium) phthalocyanine and chlorophyll a.

We report a solid-state (25)Mg NMR spectroscopic study of two magnesium-containing organic compounds: monopyridinated aqua(magnesium) phthalocyanine (MgPc.H(2)O.Py) and chlorophyll a (Chla). Each of these compounds contains a Mg(II) ion coordinating to four nitrogen atoms and a water molecule in a square-pyramidal geometry. Solid-state (25)Mg NMR spectra for MgPc.H(2)O.Py were obtained at 11.7 T (500 MHz for (1)H) for a (25)Mg-enriched sample (99.1% (25)Mg atom) using both Hahn-echo and quadrupole Carr-Purcell Meiboom-Gill (QCPMG) pulse sequences. Solid-state (25)Mg NMR spectra for Chla were recorded at (25)Mg natural abundance (10.1%) at 19.6 T (830 MHz for (1)H). The (25)Mg quadrupole parameters were determined from spectral analyses: MgPc.H(2)O.Py, C(Q) = 13.0 +/- 0.1 MHz and eta(Q) = 0.00 +/- 0.05; Chla, C(Q) = 12.9 +/- 0.1 MHz and eta(Q) = 1.00 +/- 0.05. This work represents the first time that Mg(II) ions in a square-pyramidal geometry have been characterized by solid-state (25)Mg NMR spectroscopy. Extensive quantum mechanical calculations for electric-field-gradient (EFG) and chemical shielding tensors were performed at restricted Hartee-Fock (RHF), density functional theory (DFT), and second-order Møller-Plesset perturbation theory (MP2) levels for both compounds. Computed (25)Mg nuclear quadrupole coupling constants at the RHF and MP2 levels show a reasonable basis-set convergence at the cc-pV5Z basis set (within 7% of the experimental value); however, B3LYP results display a drastic divergence beyond the cc-pVTZ basis set. A new crystal structure for MgPc.H(2)O.Py is also reported.

Journal Article↗

[Prevention of osteoporosis and pathological calcifications].

Based on physiological data about the influence of magnesium compounds on the degree of saturation of blood plasma with calcium phosphates, we have hypothesized in 1988 that magnesium deficiency is the real cause of osteoporosis and pathological calcifications. The incidence of these diseases is among the elderly as high as 40%. These diseases are the reason that there is such a discrepancy between the morbidity and mortality curve for the elderly as a function of age. Meanwhile it has been proven that a. in all osteoporotic patients the intracellular magnesium content of the erythrocytes is lower than in controls, b. this content can be restored to normal by oral magnesium supplementation without increasing the serum magnesium level, c. by this supplementation the bone density in perimenopausal women increases and d. this supplementation keeps the blood plasma and probably also the other extracellular fluids undersaturated with octocalcium phosphate so that it is impossible for pathological calcifications to occur or to progress. The possible benefits for dentistry are the following: a. perhaps mandibular resorption is retarded or inhibited by oral magnesium supplementation and b. this treatment may also help to inhibit or diminish dental calculus formation in heavy calculus formers. Since both aspects are accessible to experimental clinical investigation, we will soon have the answer to these questions.

Aged↗

Polynuclear magnesium and magnesium-titanium species. Syntheses and crystal structures of [Mg4(mu3,eta2-ddbfo)2(mu,eta2-ddbfo)2(mu,eta1-ddbfo)29eta1-ddbfo2],.

Tetranuclear magnesium complexes with chelating alkoxo ligands have been synthesized with the aim of investigating coordinatively unsaturated magnesium sites able to bind TiX4 (X = Cl, OR), of the type necessary for the formation of the active centers in polymerization catalysts. The magnesium compound [Mg4(mu3,eta2-ddbfo)2(mu,eta2-ddbfo)2(mu,eta1-ddbfo)2(eta1-ddbfo)2] x 2CH2Cl2 (1) (ddbfo = 2,3-dihydro-2,2-dimethyl-7-benzofuranoxide) was prepared by the reaction of MgBu2 with ddbfoH in dichloromethane. Complex 1 exists as a centrosymmetric tetranuclear species with two different types of magnesium centers corresponding to octahedral MgO6 and trigonal bipyramidal MgO5 geometry. Compound 1 is monoclinic, space group P2(1/c), with a = 12.053(2) A, b = 13.323(3) A, c = 17.069(3) A, beta = 98.50(3) degrees , and Z = 4. The reaction of 1 with methanol in tetrahydrofuran (THF) gave compound [Mg4(mu3-OMe)2(mu,eta2-ddbfo)2(mu,eta1-ddbfo)2(eta1-ddbfo)2(CH3OH)5] x CH3OH x THF (2). During this reaction one of the two five-coordinate MgO5 centers in 1 is completed by a methanol molecule and becomes octahedral in 2. Species 2 belongs to the P2(1/n) monoclinic space group, with a = 13.323(3) A, b = 20.768(4) A, c = 27.584(6) A, beta = 104.26(3) degrees , and Z = 4. Compound [Mg4(mu3,eta2-thffo)2(mu,zeta2-thffo)2(mu,eta1-thffo)2[mu-OTi(DIPP)3]2] x 2CH2Cl2 (3) is formed as a result of substitution of two thffo (thffo = 2-tetrahydrofurfuroxide) ligands bonded to the five-coordinate magnesium atom in [Mg4(thffo)8] by bulky OTi(DIPP)3 (DIPP = diisopropylphenolate) groups. Crystals of 3 are monoclinic, space group P2(1/n), with a = 17.069(3) A, b = 18.421(4) A, 17.815(4) A, beta = 90.77(3) degrees , and Z = 4. The X-ray crystal structures of complexes 1-3 are discussed in terms of explaining the role of the coordinatively unsaturated magnesium site in chiral catalyst active center formation.

Journal Article↗

Sorption-desorption of cadmium in aqueous palygorskite, sepiolite, and calcite suspensions: isotherm hysteresis.

Sorption isotherms have been widely used to assess the heavy metal retention characteristics of soil particles. Desorption behavior of the retained metals, however, usually differ from that of sorption, leading to a lack of coincidence in the experimentally obtained sorption and desorption isotherms. In this study, we examine the nonsingularity of cadmium (Cd) sorption-desorption isotherms, to check the possible hysteresis and reversibility phenomena, in aqueous palygorskite, sepiolite and calcite systems. Sorption of Cd was carried out using a 24-h batch equilibration experiment with eight different Cd solution concentrations, equivalent to 20-100% of maximum sorption capacity of each mineral. Immediately after sorption, desorption took place using successive dilution method with five consecutive desorption steps. Both Cd sorption and desorption data were adequately described by Freundlich equation (0.81<r(2)<0.99). The sorption and desorption reactions, however, did not provide the same isotherms, indicating that hysteresis occurred in Cd sorption-desorption processes. The extent of hysteresis was quantified based on the differences obtained from sorption and desorption isotherms regarding the amount of Cd sorbed, the Freundlich exponent, and the Cd distribution coefficient. The results revealed that, sepiolite possessed the most hysteretic behavior among the minerals studied. Calcite showed much smaller hysteresis compared to the other two silicate clays at low Cd surface load, but its hysteresis indices significantly increased, and exceeded that of palygorskite, as the amount of Cd in the systems increased. The average amount of Cd released after five desorption steps, was 13.8%, 2.2% and 3.6% for the palygorskite, sepiolite and calcite, respectively, indicating that a large portion of Cd was irreversibly retained by the minerals.

Cadmium↗

Counteractive effects of propionate or 1,2-propanediol against hypoglycemia and ketonemia of tributyrin-treated cows.

We administered tributyrin (500 ml), tributyrin (500 ml) plus magnesium propionate (400 g), tributyrin (500 ml) plus sodium propionate (400 g), or tributyrin (500 ml) plus 1,2-propanediol (400 ml) as a single dose into rumens of lactating cows and then measured in blood the plasma concentrations of glucose, acetoacetate, 3-hydroxybutyrate, free fatty acids, and insulin as a function of time. Tributyrin administration caused hypoglycemia and hyperketonemia similar to the ketotic condition in less than 3 h and was a negative correlation of --.88 between glucose and ketone concentrations in blood plasma. Administration of either magnesium propionate, sodium propionate, or 1,2-propanediol could counteract the hypoglycemia and hyperketonemia induced by tributyrin administration without significantly changing the insulin response. Of the two propionate compounds, magnesium propionate was more effective than sodium propionate for alleviating hypoglycemia and hyperketonemia.

3-Hydroxybutyric Acid↗

Effect of potassium magnesium citrate on thiazide-induced hypokalemia and magnesium loss.

The study was performed to ascertain the value of potassium magnesium citrate, magnesium citrate, and potassium citrate in overcoming thiazide-induced hypokalemia and magnesium loss. Sixty-two healthy subjects were first administered hydrochlorothiazide, 50 mg/d. After 3 weeks of thiazide treatment (or earlier for potassium level </=3.5 mEq/L), they were randomized to receive one of three drugs while continuing to receive thiazide: potassium magnesium citrate (49 mEq of potassium, 24.5 mEq of magnesium), magnesium citrate (24.5 mEq/d of magnesium), or potassium citrate (49 mEq/d of potassium). Outcome measures were changes in serum potassium and magnesium levels and urinary potassium, magnesium, pH, and citrate values. All three drugs increased serum potassium concentration compared with that resulting from thiazide alone. Potassium magnesium citrate increased serum potassium levels from 3.3 +/- 0.2 to 3.8 +/- 0.3 mEq/L (P < 0.001), potassium citrate increased serum potassium levels from 3.4 +/- 0.4 to 3.9 +/-0.3 mEq/L (P < 0.001), and magnesium citrate from 3.4 +/- 0.4 to 3.7 +/- 0.3 mEq/L (P < 0.001). Potassium magnesium citrate led to a significant increase in urinary magnesium levels by the third week of supplementation (from 120 +/- 34 to 149 +/- 58 mg/d; P < 0.01) and produced a small but significant increase in serum magnesium level. Magnesium citrate significantly increased 24-hour urinary magnesium after the first week of supplementation and maintained this increase throughout the study. Potassium magnesium citrate and potassium citrate, but not magnesium citrate, significantly increased urinary pH and citrate values. Potassium magnesium citrate not only corrects thiazide-induced hypokalemia, but also may avert magnesium loss while providing an alkali load.

Adult↗

Characteristics of pharmaceutical grade phyllosilicate compacts.

The purpose of this paper was to determine the possible employment of three groups of phyllosilicates (two smectites, three palygorskites, and two sepiolites) as direct-compression tablet excipients. Compact lots of each material were obtained after application of three different compression loads and the elastic recoveries and tensile strengths of each lot were then determined. The results showed that, in comparison with laminar minerals (smectite samples), fibrous minerals (palygorskites and sepiolites) were found to have lower elastic recovery, regardless of the compression load. Almost all elastic recovery happened immediately after the ejection of the compacts. Then, and at least during the next 24 hr, smectite compacts maintained their dimensions without any significant variation, whereas fibrous compacts tended to continue increasing slightly their dimensions. On the other hand, compacts made with laminar particles had higher mechanical strength than those made with fibrous particles, except for one sepiolite sample in which the strength was similar. Both particle morphologies and the presence or absence of hydration water molecules were taken into account in order to explain these differences. According to the compact properties measured, at least two of the noncommercial samples (smectite from Gádor, Spain, and sepiolite from Vicálvaro, Spain) would be useful as direct-compression tablet excipients.

Chemistry, Pharmaceutical↗

Nebulized magnesium sulfate in the management of acute exacerbations of asthma.

OBJECTIVE: To evaluate the efficacy and safety of nebulized magnesium sulfate in the treatment of acute exacerbations of asthma. DATA SOURCES: MEDLINE, EMBASE, and PubMed (all to October 2005) were searched using the key words magnesium, magnesium sulfate, magnesium compounds, nebulise, nebulize, vaporise, vaporize, nebulizers and vaporizers, aerosols, asthma, exacerbation, bronchial spasm, and bronchospasm. STUDY SELECTION AND DATA EXTRACTION: Prospective, randomized, controlled trials that evaluated efficacy and safety endpoints of nebulized magnesium sulfate in the management of acute exacerbations of asthma were included. All studies were evaluated independently by both authors. Efficacy outcomes included pulmonary function, clinical disease severity (as defined by each study), and rate of hospitalization. Safety outcomes were as described by each trial. DATA SYNTHESIS: Six prospective trials met the study criteria. Nebulized magnesium alone failed to demonstrate any benefit compared with beta(2)-agonists alone at improving pulmonary function. In trials in which nebulized magnesium was used as a vehicle for albuterol, there appear to be additional benefits to albuterol therapy in terms of improvements in pulmonary function in a population with mild-to-moderate asthma. The heterogeneous patient populations, study designs, magnesium doses, and the delivery methods preclude the extrapolation of these results to current clinical practice. CONCLUSIONS: The studies included in this review fail to clarify the role of nebulized magnesium sulfate; therefore, this therapy cannot be recommended at this time. Future studies evaluating the role of nebulized magnesium as an adjunct therapy to beta(2)-agonist, anticholinergic, and corticosteroid therapy are necessary to determine whether a clinically relevant benefit of this intervention exists.

Acute Disease↗

One-dimensional filtration of pharmaceutical grade phyllosilicate dispersions.

The filtration behaviour of some clay-water dispersions was studied. Two Spanish fibrous phyllosilicates (sepiolite from Vicálvaro and palygorskite from Turón) and a commercial bentonite (Bentopharm UK) with similar sizes and different morphologies (fibrous and/or laminar) were selected as model clays. Sepiolite from Vicálvaro is an almost pure fibrous sample, Bentopharm presents a high amount of laminar particles and palygorskite from Turón is made up of similar percentages of laminar and fibrous particles. The disperse systems were made up using a rotor-stator mixer working at two different mixing rates (1000 and 8000 rpm), for periods of 1 and 10 min. Filtration measurements were taken and the corresponding filtration curves obtained. Finally, the desorptivity (S) of the filtration cakes was calculated and correlated to the textural characteristics of the materials, the solid fraction and mixing conditions. Filtration behaviour of the dispersions depended on all three of these factors. Laminar dispersions presented lower S values than fibrous dispersions. In the 2% w/v dispersions the bridging forces between particles did not permit formation of an interconnected network as in 10% w/v dispersions and, consequently, filtration times increased with the solid fraction (i.e. S values decreased). Regarding stability to pH changes, the results showed that filtration behaviour was highly sensitive to basic pH in the fibrous clay dispersions and almost insensitive in the laminar clay dispersions.

Aluminum Silicates↗

Pharmaceutical grade phyllosilicate dispersions: the influence of shear history on floc structure.

The effect of mixing conditions on the flow curves of some clay-water dispersions was studied. Two Spanish fibrous phyllosilicates (sepiolite from Vicálvaro and palygorskite from Turón) and a commercial bentonite (Bentopharm Copyright, UK) were selected as model clays. The disperse systems were made up using a rotor-stator mixer working at two different mixing rates (1000 and 8000 rpm), for periods of 1 and 10 min. Rheological measurements were taken and the corresponding flow curves obtained immediately after interposition and then after a period of 24 h under low shear caused by a roller apparatus. Aqueous sepiolite dispersions showed the highest viscosity and were easily interposed, whereas palygorskite dispersions were more difficult to obtain, resulting in low to medium viscosity gels. Bentonite dispersions provided medium viscosity systems, which greatly increased their viscosity after the low shear treatment (as a result of swelling), whereas the viscosity of the fibrous clays stayed at approximately the same values or even decreased. A linear relation was found between mixing energy and apparent viscosity in the bentonite systems, while apparent viscosity in the sepiolite samples was related to mixing power, with minor influence of mixing times. All the systems studied had thixotropic behaviour, changing from clearly positive to even negative thixotropy in some palygorskite systems. Finally, we studied the effect of drastic pH changes on the system structure. Results showed that rheological properties were highly sensitive to pH in the fibrous dispersions, but less sensitive behaviour was found in the laminar clay systems.

Aluminum Silicates↗

Polyamines and acetylpolyamines increase the stability and alter the conformation of nucleosome core particles.

The interactions of spermine (4+ charge at physiological pH), N1-acetylspermine(3+), spermidine(3+), N1- and N8-acetylsperimidine(2+), putrescine(2+), hexaamminecobalt(3+), and magnesium(2+) with nucleosome core particles have been examined by using thermal denaturation and circular dichroism. Tetra- and triamines were 2-3 times more effective than diamines at stabilizing core particles against thermal denaturation. Secondary effects were also observed, with acetylpolyamines slightly less effective than unmodified polyamines of equivalent charge. Hexaamminecobalt(3+) was less effective than the triamines, while magnesium had essentially no effect. This is surprising since magnesium is more effective than diamines at stabilizing naked DNA. All the cations tested altered the circular dichroism spectra of the core particles in the DNA region (284 nm). The peak at 284 nm was suppressed by tetra- and trivalent compounds to approximately twice the extent of divalent compounds. Magnesium appears to suppress the peak by a lesser extent than the diamines. This indicates that the DNA twist and/or folding is changed by these cations. A plateau of both thermal denaturation and circular dichroism effects was observed at cation concentrations where 30-40% of the total DNA negative charges could be neutralized by the added cations. We suggest that polyamine and histone acetylation function in concert to lower the stability and change the conformation of the nucleosome core, thus facilitating replication and transcription in vivo.

Animals↗

Effect of varying doses of potassium-magnesium citrate on thiazide-induced hypokalemia and magnesium loss.

The purpose of this study was to compare the efficacy of three dosages of potassium-magnesium citrate in overcoming thiazide-induced hypokalemia and magnesium loss and increasing urinary pH and citrate. Sixty-one normal subjects first took hydrochlorothiazide at 50 mg/d. After 3 weeks of thiazide treatment or earlier if hypokalemia developed, the subjects were randomized to take one of three dosages of potassium-magnesium citrate (K ( 4 ) MgCit ( 2 ) ) for 3 weeks while continuing on the thiazide: 4 tablets per day (24 mEq potassium, 12 mEq magnesium, and 36 mEq citrate per day), 7 tablets per day (49 mEq potassium, 24.5 mEq magnesium, and 73.5 mEq citrate per day), or 10 tablets per day (70 mEq potassium, 35 mEq magnesium, and 105 mEq citrate per day). Outcome measures were changes in serum potassium and magnesium and urinary potassium, magnesium, pH, and citrate. All three dosages of potassium-magnesium citrate significantly increased serum potassium concentration, with >80% of subjects regaining normal values despite continued thiazide therapy. The two higher dosages, but not the lowest dosage, caused a small but significant increase in serum magnesium concentration, while substantially increasing urinary magnesium. All three dosages significantly increased urinary pH and citrate in a dose-dependent manner. The lowest dosage produced increases sufficient to prevent stone recurrence. Side effects of thiazide therapy were ameliorated by the highest dosage but not by the two lower dosages. Potassium-magnesium citrate at a dosage of 4 tablets per day is adequate to correct thiazide-induced hypokalemia and to increase urinary pH and citrate sufficiently for stone prevention. Higher dosages are probably required for the prevention of magnesium loss and adverse symptoms of thiazide therapy.

Adult↗

On the use of parenteral magnesium salts in the treatment of acute ischaemic heart disease: a brief review.

With the advent of pharmacological, mechanical and surgical revascularization as firstline therapies in acute coronary artery disease syndromes, the search for adjunctive pharmacotherapy against reocclusion and reperfusion injury has intensified. In addition, safe pharmacotherapeutic intervention conferring survival advantage is required for those at high risk ineligible for recanalization or beta blockade. Of major importance, in this vein, is the intriguing association between parenteral magnesium and the amelioration of myocardial ischaemia and the eradication of lethal ischaemic ventricular arrhythmias reasserted in both animal and human studies. In addition, in more recent years, parenteral magnesium has been linked to the amelioration of reperfusion injury in animal experiments. In this paper we shall review the literature with respect to myocardial ischaemia, its pathophysiology and treatments. In doing so, we shall present data that strongly supports the logistic use of parenteral magnesium compounds as essential therapy in the treatment of acute ischaemic heart disease associated with necrosis, and a potential role in ablating reperfusion injury.

Electrophysiology↗

Reperfusion effects on the magnesium-procaine arrested rabbit heart.

Rabbit hearts were subjected to cardiac arrest induced by injecting 3 isotonic cardioplegic solutions each of which contained in combination with procaine-HCl one of 3 different magnesium compounds. A period of 40 min arrest was followed by reperfusion of 15 min. A regular sinus rhythm returned after washout of the cardioplegic solution. The pattern of the essentially unaltered myocardial ultrastructure correlated with the well-preserved high-energy phosphate stores. The effects of magnesium and procaine on cell permeability and the consequences of the different fusion are discussed. The study stresses the importance of an adequate period of postischemic reperfusion of the heart in an unloaded state in support of myocardial recovery. The studies presented herein suggest further investigations of various concentrations of magnesium and procaine combined with different amounts of calcium in perfusates for the preservation of the heart and possibly of other organs.

Animals↗

Magnesium studies in hemodialysis patients before and after treatment with low dialysate magnesium.

The magnesium status of 22 hemodialysis patients was studied by analyses of serum, skeletal muscle and peripheral blood lymphocyte levels of magnesium. Despite elevated serum magnesium, normal magnesium levels were noted in skeletal muscle and lymphocytes. 12 patients were exposed to a low dialysate magnesium concentration, resulting in normalization of serum magnesium but no changes in muscle or lymphocyte magnesium, which might indicate slow exchange between these intracellular stores and the extracellular fluid. Normalization of serum magnesium was followed by a slight rise in circulating parathyroid hormone levels without noticeable changes in serum calcium or phosphate levels. Since signs of an absolute magnesium excess were not detected, a combination of low dialysate magnesium and the use of an oral magnesium compound as a phosphate binder might be a way to decrease aluminium exposition in hemodialysis patients.

Alkaline Phosphatase↗

Headache due to photosensitive magnesium depletion.

Clinical and paraclinical data (visual stress tests, electroencephalographic and cerebrovascular photic driving, visual evoked potentials) demonstrate that the concept of photosensitive headache is fully justified. The interictal hallmark of photosensitive cephalalgic patients is potentiation (or sensitization) instead of habituation. The aetiopathogenic mechanisms of photosensitive headache associate hypofunction of the biological clock and magnesium depletion. The new concept of headache due to photosensitive magnesium depletion seems justified. It appears logical to add the treatments of magnesium depletion and of photosensitivity to classical treatment of headache. Prophylactic magnesium treatment relies on atoxic nutritional magnesium supplementation in case of primary magnesium deficiency. Pharmacological doses of parenteral magnesium may be used but may induce toxicity. Therefore it is necessary to know the therapeutic index of magnesium compound used: the larger its value, the greater the safety margin. Treatment of photosensitivity uses various types of < >: darkness therapy through physiologic, psychotherapic, physiotherapic, pharmacologic stimulating techniques and substitutive darkness therapy through palliative treatment. Melatonin is only a partial substitutive treatment of photosensitivity. A new model of photosensitive magnesium depletion with potentiation should be a useful tool for discriminating the most efficient gent.

Biological Clocks↗