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Magnesium and gastric acid secretion.

This study examined the modifications of acid gastric secretion caused by magnesium oxide, peroxide, silicate and sulphate in 805 patients with duodenal ulcers; The calcium-magnesium antagonism on the one hand and the acetazolamide - magnesium synergia on the other, were also investigated. Our results show that administration of magnesium, either oral or parenteral, does not significantly modify gastric acid secretion, either basal or stimulated by maximal histamine. Administration of un infusion of calcium gluconate 15 mg/kg body weight, significantly increases gastric acid secretion as compared to basal secretion. Addition of a dose of magnesium sulphate to the infusion antagonises the effect of gastric acid secretion caused by calcium. Administration of 1.5 gr magnesium oxide along with 25 mg acetazolamide per kg/body weight, strengthens the inhibitory effect of acetazolamide upon gastric acid secretion, increasing the proportion of significant inhibitory effects up to 98% of the cases under investigation. Addition of magnesium to the classical therapy antagonises the noxious effects of calcium compounds; the presence of magnesium in the composition of antacid powders proves necessary.

Adult↗

Correction of thiazide-induced hypomagnesemia by potassium-magnesium citrate from review of prior trials.

PURPOSE: To ascertain whether hypomagnesemia develops during short-term thiazide treatment in normal subjects and if it can be corrected by potassium-magnesium citrate (Relyte) supplementation. METHODS: Serum magnesium data were retrieved from 242 normal subjects from prior 4 trials. After 1-3 weeks of treatment with hydrochlorothiazide 50 mg/day, subjects received supplementation with Relyte or a related compound while continuing on thiazide for 3 weeks. RESULTS: Hypomagnesemia (< or =1.8 mg/dl) was disclosed in 19.4% of 242 subjects on thiazide alone. In such patients, Relyte treatment significantly increased serum magnesium concentration to the normal range, whereas supplementation with potassium citrate or potassium chloride did not. In the Relyte group comprised of 131 subjects, the frequency of hypomagnesemia decreased from 22.9% on thiazide alone to 4.6% after 4 weeks of Relyte supplementation. In contrast, the frequency of hypomagnesemia displayed a non-significant increase from 15.7% on thiazide alone to 20-24% on potassium citrate or potassium chloride. CONCLUSION: Mild hypomagnesemia develops in about one fifth of normal subjects during short-term thiazide treatment. Relyte can readily correct it.

Benzothiadiazines↗

Studies on the loss of infectivity of live type 3 poliovaccine on storage.

The Children's Vaccine Initiative established a Product Development Group in 1991 to help in the development of oral poliovaccines of improved thermostability. Under the auspices of this group, the effect of different stabilizers on the loss of infectivity of commercial monovalent type 3 live poliovaccine bulks at 37 degrees C, 42 degrees C and 45 degrees C has been examined. The only effective conditions were the maintenance of the pH at 6.5, and the use of deuterium oxide at a concentration of 90%. All other additives, including detergents, albumin, antiviral compounds, sucrose and magnesium chloride, alone or in combination either had no effect or increased the rate of loss of infectivity.

Antiviral Agents↗

Synthesis and Characterization of Dimeric Mutually Coordinated Magnesium meso-2-Pyridylporphyrins.

The synthesis and characterization of a series of meso-2-pyridylporphyrins and their Mg(2+) complexes are reported. Condensation of 4-alkylbenzyl-2,2'-dipyrromethanes (alkyl = Me, n-Pr, or n-Bu) with 2-pyridinecarboxaldehyde yielded a series of free-base meso-2-pyridylporphyrins. Insertion of Mg(2+) into the free-base porphyrins yielded the respective magnesium complexes. These compounds were characterized using 1D ((1)H and (13)C) and 2D ((1)H-(1)H COSY) NMR methods, UV-visible absorption spectroscopy, fluorescence spectroscopy, and mass spectrometry. The interplanar spacing of the dimers is sufficiently small that there is excitonic coupling of the constituent chromophores. The overall dissociation constant of these dimers is estimated at 2 x 10(-)(6) M. Addition of donor ligands such as acetone, DMF, DMSO, or pyridine converts the dimeric species to their respective constituent monomers. Titration of the dimeric complex with pyridine-d(5)() shows that disaggregation requires coordination of two pyridine molecules at independent binding sites. Tracking of the pyridine coordination by (1)H NMR spectroscopy allowed for determination of the equilibrium constant for the pyridine-induced disaggregation reaction (2.1 x 10(-)(3) M(2)). Both the spontaneous dissociation and the pyridine-induced disaggregation reactions occur by two steps.

Journal Article↗

Regioselectivity in the addition of vinylmagnesium bromide to heteroarylic ketones: C- versus O-alkylation.

The reactivity of heteroarylic ketones toward vinylmagnesium bromide (2) and the regiochemistry of the addition were investigated. The reactivity drastically increases when the carbonyl is conjugated with at least one aza group and the regiochemistry of the addition of the vinyl Grignard reagent depends on the carbonyl compound: in the series of di(heteroazolyl) ketones the O-alkylation product was observed as unique with di(1,3-benzothiazol-2-yl) ketone, and in different relative ratios with respect to the classic C-alkylation product with di(1,3-thiazol-2-yl) ketone, (1,3-benzothiazol-2-yl) (1,3-thiazol-2-yl) ketone, and di(1,3-benzoxazol-2-yl) ketone, whereas di(N-methylbenzimidazol-2-yl) ketone gave the exclusive formation of the carbinol. This behavior can be explained by the intervention of the delocalization power of the heterocyclic ring and this was confirmed by the results obtained from the reaction between vinylmagnesium bromide and a series of mixed (1,3-benzothiazol-2-yl) (para-substituted phenyl) ketones, that showed a relative O-/C-alkylation ratio dependent on the nature and on the electronic effect of the substituent on the phenyl ring. The results are in agreement with the existence of intermediate species bearing a negative charge on the benzylic carbonyl carbon atom, and make the O-alkylation reaction between vinyl Grignard reagents and carbonyl compounds no longer a rare case, since it was observed with a number of heterocyclic carbonyl compounds, such as (1,3-benzothiazol-2-yl) aryl ketones and di(heteroaryl) ketones of the pentatomic 1,3-heteroazolic series.

Alkylation↗

Synaptojanin inhibition of phospholipase D activity by hydrolysis of phosphatidylinositol 4,5-bisphosphate.

A 150-kDa protein that inhibits phospholipase D (PLD) activity stimulated by ADP-ribosylation factor and phosphatidylinositol 4, 5-bisphosphate (PI(4,5)P2) was previously purified from rat brain. The sequences of peptides derived from the purified PLD inhibitor now identify it as synaptojanin, a nerve terminal protein that has been implicated in the endocytosis of fused synaptic vesicles and shown to be a member of the inositol polyphosphate 5-phosphatase family. Further characterization of the enzymatic properties of synaptojanin now shows that it hydrolyzes only the 5-phosphate from inositol 1,4,5-trisphosphate (I(1,4,5)P3) and that it does not catalyze the dephosphorylation of either I(1,3,4)P3 or inositol 1, 4-bisphosphate. However, synaptojanin hydrolyzes both the 4- and 5-phosphates of PI(4,5)P2 and the 4-phosphate of phosphatidylinositol 4-phosphate, converting both compounds to phosphatidylinositol. Magnesium is required for the hydrolysis of I(1,4,5)P3, but not for that of phosphoinositides, by synaptojanin. The inhibition of PLD by synaptojanin is attributable to its ability to hydrolyze PI(4,5)P2. Synaptojanin did not inhibit PLD in the absence of PI(4,5)P2, and the extent of PLD inhibition was related to the extent of PI(4,5)P2 hydrolysis in substrate vesicles. It has been proposed that the biosynthesis of PI(4,5)P2 and the activation of PLD by ADP-ribosylation factor constitute a positive loop to increase rapidly the concentrations of PI(4,5)P2 and phosphatidic acid (PA) during membrane vesiculation. The PA thus produced, probably together with PI(4,5)P2, facilitates vesicle coat assembly. The hydrolysis of PI(4,5)P2, and consequent inhibition of PLD, by synaptojanin might therefore constitute a mechanism to halt the positive loop connecting PI(4,5)P2 and PA during the endocytotic cycle of synaptic vesicles and serve as a signal for uncoating.

Amino Acid Sequence↗

Characterization of the interaction between annexin I and profilin.

Annexin I belongs to a family of calcium-dependent phospholipid-binding and membrane-binding proteins. Although many of the biochemical properties and the three-dimensional structure of this protein are known, its true physiological roles have yet to be thoroughly defined. Its putative functions include participation in the regulation of actin microfilaments dynamics, proposed after the discovery of an interaction with actin. In accordance with this hypothesis, we found that annexin I can also interact with profilin. We used different methods, overlay and surface plasmon resonance (BIAcore), to measure the parameters of the association equilibrium, i.e. k(on), k(off) and k(d). The affinity of annexin I for profilin was between 10(7) M and 10(8) M. High concentrations of KCl did not prevent the interaction, although a slight decrease in affinity was observed. Calcium, a modulator of annexin I functions interfered only marginally with the association, in a manner comparable to magnesium. Proteins or compounds known to interact with annexin I or profilin were found to inhibit the annexin-I--profilin interaction when added in the reaction medium. Recombinant profilin exhibited a slightly lower affinity than natural platelet protein when measured with BIAcore. Due to the submembrane localisation of annexin I and the regulatory activity of profilin on the cytoskeleton, an interaction between annexin I and profilin may therefore be implicated in the regulation of some cellular functions, particularly those governing membrane-cytoskeleton dynamic organization.

Actins↗

Microthrix parvicella, a filamentous bacterium isolated from activated sludge: cultivation in a chemically defined medium.

A large number of media have been tested for cultivating Microthris parvicella, a filamentous microorganism often present in the activated sludge of oxidation ditches. The bacterium was found to utilize oleic acid (preferably as Tween 80) as the sole source of carbon and energy. Sulfur is required in the reduced form. The tested media vary from a complex to a chemically defined medium. Growth yields of 1.3 to 1.5 g/liter were obtained on media containing Tween 80 (4 g/liter), reduced nitrogen and reduced sulfur compounds, calcium and magnesium salts, phosphate buffer, trace elements, thiamin, and cyanocobalamin. The optimum temperature for growing the organism is approximately 25 degrees C, and the pH of the nutrient medium should be above 7.

Culture Media↗

Characterization of a naturally occurring diamine auxotroph of Veillonella alcalescens.

Veillonella alcalescens strain ATCC 17745 was shown to require putrescine or cadaverine for growth. None of the other compounds tried, including magnesium and spermidine, were able to substitute for the diamines. Studies with labeled diamines showed that spermidine was made from putrescine in this organism. A polyamine analogous to spermidine, but made from cadaverine, was not found. A combination of growth experiments and chemical assays suggested that protein synthesis was limited in diamine-starved cells. Protein synthesis occurred prior to nucleic acid synthesis when putrescine was added to starved cells.

Bacterial Proteins↗

Metal ions suppress the abnormal taste behavior of the Drosophila mutant malvolio.

A mutation in the malvolio (mvl) gene affects taste behavior in Drosophila melanogaster. The malvolio gene encodes a protein (MVL) that exhibits homology to the mammalian natural resistance-associated macrophage proteins. It is also homologous to the Smf1 protein from Saccharomyces cerevisiae, which we have recently demonstrated to function as a Mn2+/Zn2+ transporter. We proposed that the Drosophila and mammalian proteins, like the yeast SMF1 gene product, are metal-ion transporters. To test this hypothesis, malvolio mutant flies were allowed to develop, from egg to adulthood, on a medium containing elevated concentrations of metal ions. Mutant flies that were reared in the presence of 10 mmol l-1 MnCl2 or FeCl2 developed into adults with recovered taste behavior. CaCl2 or MgCl2 had no effect on the mutant's taste perception. ZnCl2 inhibited the effect of MnCl2 when both ions were supplied together. Similar suppression of the abnormal taste behavior was observed when mvl mutants were fed MnCl2 or FeCl2 only at the adult stage. Furthermore, exposure of adult mutant flies to these ions in the testing plate for only 2 h was sufficient to restore normal taste behavior. The suppression of the defective taste behavior suggests that MVL functions as a Mn2+/Fe2+ transporter and that Mn2+ and/or Fe2+ are involved in the signal transduction of taste perception in Drosophila adults.

Animals↗

[Renal failure--concepts for drug therapy in intensive care].

This article describes concepts of drug treatment for patients with severe renal failure (creatinine clearance less than 10 ml/min), especially in intensive care. These subjects often develop multiorgan failure and require special considerations: 1. Not only should the maintenance dose of digoxin be reduced to 0.05-0.1 mg/day, but the loading or digitalizing dose should also be diminished to 0.4-0.6 mg. 2. Penicillins, cephalosporins, quinolones, and other antibiotics with a high therapeutic ratio can be given as recommended by the manufacturer or reference lists according to renal insufficiency. 3. For drugs with a low therapeutic index, such as aminoglycosides, vancomycin, flucytosine, some antiarrhythmic agents, cardiac glycosides, and theophylline, therapeutic drug monitoring is mandatory. 4. Steroids, insulin, atropine, catecholamines, anticoagulants, thrombolytic agents, antihypertensive drugs, and organic nitrates can be given according to their effect. However, nitroprusside should be discontinued after 2 days because its metabolites may be toxic. 5. The dose of H2-receptor antagonists used for the control of gastric acidity and the treatment of peptic ulcers should be reduced to 20-50% of the normal. The administration of aluminum, magnesium, and bismuth compounds should be avoided. 6. Loop diuretics (e.g., furosemide) can be effective at increased doses in patients with chronic renal failure and fluid overload, particularly when used in combination with a thiazide in refractory edema. Thiazides alone are useless, and potassium-sparing diuretics are contraindicated. 7. Colloid-containing solutions should be infused cautiously at a maximal rate of 2 x 500 ml/week only when the plasma volume is contracted.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗

[Utilization of mycelial waste of antibiotic production in the technology of kilned construction materials].

At present the main part of the mycelial waste of antibiotic production is collected in sludge lagoones, discarded to the sewage treatment system or burnt. The mycelial waste is one of the causes of the environmental pollution. It contains a significant quantity of valuable substances, such as lipids, carbohydrates, proteins and amino acids. The inorganic portion of the waste includes the compounds of calcium, magnesium, sodium, iron, silicium and phosphorus. The levels of the above substances in the mycelial waste allow using it as organic mineral additives in making expanded clay aggregate gravel with the use of low quality clay and loam. It may be also used as the burn-out of the raw material charge in making burnt bricks and other burnt building materials. By its calorific value the mycelial waste is equal to brown coal or peat. It was shown that the structural and mechanical properties of the mixtures of the mycelium and clay depended on the moisture content of the composition and the proportion of its components. The mycelial waste provided a decrease in the optimal temperature of burning by 40-50 degrees C. The production tests at the expanded clay aggregate plants showed that the bulk weight of expanded clay aggregate might be lowered by 50-100 kg/m3 and the usual additives with the use of petroleum products might be completely excluded from the technological process. The use of the mycelial waste for manufacture of burnt building materials provides saving of the fuel energy sources and improvement of the quality of the finished product. It is also important from the ecological viewpoint.

Anti-Bacterial Agents↗