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Intestinal adsorption of levothyroxine by antacids and laxatives: case stories and in vitro experiments.

Two patients with hypothyroidism treated for upper dyspepsia and constipation with aluminum hydroxide and magnesium oxide, respectively, presented a marked increase in the serum concentration of thyroid stimulating hormone and low serum thyroxine on a fixed dosage of levothyroxine. After discontinuation of antacids/laxatives, thyroid stimulating hormone was again reduced indicating interaction between levothyroxine and antacids/laxatives. In vitro studies revealed a dose-related increased adsorption of levothyroxine by addition of a combination of aluminum hydroxide, magnesium hydroxide and magnesium carbonate, while no connection between levothyroxine and the addition of magnesium oxide, alone, was found. This finding has major clinical consequences since 1) many patients are treated with levothyroxine, 2) most patients do not tell physicians that they take antacids/laxatives, and 3) consumption of antacids/laxatives in patients with levothyroxine-treated hypothyroidism may lead to serious undersubstitution with levothyroxine.

Adsorption↗

Effect of age and magnesium administration on the performance of SHR in the elevated plus-maze.

It is currently accepted that young spontaneously hypertensive rats (SHR) have lower pressure levels than adult SHR in which the hypertension is well established, reaching the highest plateau at about 24 weeks, and that treatment with magnesium initiated during intrauterine life postpones the onset of cardiovascular alterations in SHR to about 90 days. These animals also show many behavioral alterations. The anxiety of SHR was measured in the elevated plus-maze, considering the age of the animals and previous ingestion of food supplemented with 1% magnesium oxide. Both young (1.5-2 months) and adult (5-6 months) SHR showed higher mean ( +/- SEM) percent of entries (48 +/- 3 and 51 +/- 3, respectively) and a longer mean ( +/- SEM) percent of time spent (43 +/- 5 and 55 +/- 5, respectively) in the open arms when compared to the mean ( +/- SEM) percent of entries and time spent in the open arms of young (35 +/- 3 and 20 +/- 4, respectively) and adult (36 +/- 7 and 17 +/- 5, respectively) normotensive Wistar rats. Treatment with magnesium oxide did not alter the performance of SHR in the elevated plus-maze. SHR showed an anxiolytic-like behavior which was neither influenced by age nor by antihypertensive treatment.

Age Factors↗

Effects of a combination of evening primrose oil (gamma linolenic acid) and fish oil (eicosapentaenoic + docahexaenoic acid) versus magnesium, and versus placebo in preventing pre-eclampsia.

In a placebo controlled, partially double-blinded, clinical trial, a combination of evening primrose oil and fish oil was compared to Magnesium Oxide, and to a Placebo in preventing Pre-Eclampsia of Pregnancy. All were given as nutritional supplements for six months to a group of primiparous and multiparous pregnant women. Some of these women had personal or family histories of hypertension (21%). Only those patients who received prenatal care at the Central Maternity Hospital for Luanda were included in the study. Compared to the Placebo group (29%), the group receiving the mixture of evening primrose oil and fish oil containing Gamma-linolenic acid (GLA), Eicosapentaenoic acid (EPA), and Docosahexaenoic acid (DHA) had a significantly lower incidence of edema (13%, p = 0.004). The group receiving Magnesium Oxide had statistically significant fewer subjects who developed hypertension of pregnancy. There were 3 cases of eclampsia, all in the Placebo group.

Adolescent↗

Addition of buffers to high quality alfalfa hay-based diets for dairy cows in early lactation.

Beginning 4 wk postpartum, 14 Holstein cows were paired according to expected calving date and lactation number and assigned randomly to one of two treatments in a single reversal experiment designed to study the effects of added buffers to high quality alfalfa hay-based diets. Cows were offered daily 14.5 kg of concentrate containing 0 or 2% sodium bicarbonate and .5% magnesium oxide (as fed), plus free choice high quality alfalfa hay in a ratio of forage:grain approaching 50:50 (dry matter). No differences were in milk production, milk fat percentage, fat-corrected milk, or dry matter intake. Dry matter intake of grain was decreased with addition of buffers. Kilograms fat-corrected milk per kilogram of dry matter intake were 1.41 and 1.45 for control and buffered diets. No differences were significant for rumen pH, ammonia concentration, molar proportions of acetate and propionate, or ratio of acetate: propionate. Concentrations of total volatile fatty acids were higher for cows fed the buffered diet. No differences were in blood acid-base status or in various serum metabolites. Urine pH was 8.11 and 8.20 for control and buffered diets. Fractional urinary excretion of magnesium and sodium was greater when cows consumed the buffered diet. Diet digestibilities and rate of passage were not affected by dietary buffers. Addition of sodium bicarbonate plus magnesium oxide did not improve performance of early lactation cows fed high quality alfalfa hay as the sole forage.

Animal Feed↗

Nonsurgical management of partial adhesive small-bowel obstruction with oral therapy: a randomized controlled trial.

BACKGROUND: Patients with partial adhesive small-bowel obstruction are usually managed conservatively, receiving intravenous hydration and nothing by mouth. Previous studies have suggested that this approach is associated with longer hospital stays and an increased risk of delayed surgery. We conducted a randomized controlled trial to see if combining standard conservative treatment with oral administration of a laxative, a digestant and a defoaming agent would reduce the frequency of subsequent surgical intervention and reduce the length of hospital stay. METHODS: We identified 144 consecutive patients admitted between February 2000 and July 2001 with adhesive partial small-bowel obstruction and randomly assigned 128 who met the inclusion criteria to either the control group (intravenous hydration, nasogastric-tube decompression and nothing by mouth) or the intervention group (intravenous hydration, nasogastric-tube decompression and oral therapy with magnesium oxide, Lactobacillus acidophilus and simethicone). The primary outcome measures were the number of patients whose obstruction was successfully treated without surgery and the length of hospital stay. We also monitored rates of complications and recurring obstructions. RESULTS: Of the 128 patients, 63 were in the control group and 65 in the intervention group; the mean ages were 54.4 (standard deviation [SD] 15.9) years and 53.9 (SD 16.3) years respectively. Most of the patients were male. More patients in the intervention group than in the control group had successful treatment without surgery (59 [91%] v. 48 [76%], p = 0.03; relative risk 1.19, 95% confidence interval 1.03-1.40). The mean hospital stay was significantly longer among patients in the control group than among those in the intervention group (4.2 [SD 2.7] v. 1.0 [SD 0.7] days, p < 0.001). The complication and recurrence rates did not differ significantly between the 2 groups. INTERPRETATION: Oral therapy with magnesium oxide, L. acidophilus and simethicone was effective in hastening the resolution of conservatively treated partial adhesive small-bowel obstruction and shortening the hospital stay.

Administration, Oral↗

In vitro antidiabetics-antacid interactions.

The adsorption of the oral antidiabetics metformin hydrochloride, glibenclamide, acetohexamide, tolbutamide, carbutamide, tolazamide and glymidine on various antacids or adsorbents was studied at 37 degrees C. The antacids or adsorbents used were magnesium trisilicate, aluminium hydroxide, calcium carbonate, magnesium oxide, bismuth oxycarbonate, talc, kaolin as well as charcoal. None of the substances tested, with the exception of charcoal, exhibited superior adsorptive properties for all the drugs. Magnesium trisilicate and calcium carbonate were the best adsorbents for metformin hydrochloride. Acetohexamide and glibenclamide were adsorbed to an appreciable extent on most antacids. Tolbutamide showed an adsorption tendency towards talc. Most antacids slightly adsorbed carbutamide, while magnesium trisilicate showed a higher adsorption capacity for tolazamide and glymidine. The dissolution rate of acetohexamide in magnesium oxide suspension (5:400) increased about 40-fold after 10 min, whle in magnesium trisilicate suspension (5:400) it increased about 7-fold. On the other hand, magnesium trisilicate did not influence the dissolution rate of metformin hydrochloride. The probable variation in the bioavailability of orally administered antidiabetics when coadministered with antacids was discussed. However, further in vivo studies are needed before a final assessment for such drug-antacid interaction can be confirmed.

Adsorption↗

Blood plasma magnesium, potassium, glucose, and immunoreactive insulin changes in cows moved abruptly from barn feeding to early spring pasture.

Cations and immunoreactive insulin in plasma were measured in 35 lactating cows moved abruptly to early spring pasture. After change of cows from grass-clover hay to fescue-bluegrass pasture containing 22 to 31 g potassium/kg dry matter, immunoreactive insulin of 5 Holstein cows increased 30% in 5 days and averaged 45% above prepasture concentrations for 40 days. Magnesium averaged 44% below prepasture content of plasma during this period and was correlated negatively with potassium -.17 and immunoreactive insulin -.37. Thirty Herford cows were changed from corn silage and grass-clover hay to wheat-rye pasture containing 3.06% potassium in the dry matter. Each day on pasture, 10 cows each were fed 2.3 kg cornmeal, 10 were given 30 g magnesium oxide by capsule, and 10 were given no supplement. After unsupplemented cows were moved to pasture, immunoreactive insulin rose 51% in 8 days and plasma magnesium fell 24%. Both supplements reduced immunoreactive insulin, but magnesium was maintained higher by magnesium oxide than by cornmeal. Injection of two Holstein cows with insulin (2 IU/kg body weight) reduced plasma concentrations of both potassium and magnesium 20% below that of two cows injected with only physiological saline. Whether elevated plasma insulin may accelerate development of hypomagnesemia in cattle on spring pasture with relatively high potassium content has not been established.

Animal Husbandry↗

Performance, blood and ruminal characteristics of cows receiving monensin and a magnesium supplement.

Forty-eight Angus and Hereford cows were used in a completely random design with a 2 X 2 factorial arrangement of treatments to evaluate the effects of monensin and two sources of Mg on performance, ruminal characteristics and mineral status of mature beef cows. Cows were fed wheat straw treated with NH3 during late gestation and straw treated with NH3 plus bromegrass haylage after calving along with a protein supplement that contained either MgO (7.5 g/kg) or MgSO4 (11 g/kg). One half of the cows received monensin (1 g/kg) in their protein supplement. During the precalving period, MgO without monensin increased (P less than .01) plasma Mg compared with Mg in plasma of cows receiving MgSO4 or MgO with monensin. Magnesium oxide also increased cow weight gains during late gestation (P less than .05) compared with weight gains of cows supplemented with MgSO4, but magnesium source had no effect on weight gain postcalving. Plasma glucose was increased by monensin (P less than .05) and by MgSO4 (P less than .01) during early lactation. Monensin increased the proportion of propionate before (P less than .05) and after (P less than .10) calving in the ruminal fluid of cows. Monensin also increased (P less than .05) cow weight gain precalving and tended to decrease (P less than .10) milk fat in lactating cows. Calf weight gains were not affected by treatment of dam. Magnesium oxide appeared to have higher Mg bioavailability than MgSO4 for cows precalving, but Mg bioavailability was not different postcalving. Monensin increased cow weight gains precalving and improved feed efficiency postcalving.

Animals↗

Bond energies for molecules, clusters, and deposit systems.

A new approach is suggested to the assignment of bond energies in molecules and clusters. It uses a shareholder principle for the redistribution of the shifts in atomic energies, which arise in a molecule, on the bonds. The scheme is directly suitable for semiempirical methods, where only one- and two-center terms occur. MSINDO calculations are performed to demonstrate the suitability of the approach for molecules and clusters. As an application the bonding in a deposit system is analyzed for the case of copper on magnesium oxide. It is found that copper atoms do not only bind to the preferred oxygen sites but also substantially to the magnesium sites. The copper-copper bonds are the strongest and will determine the structure of copper clusters on magnesium oxide surfaces.

Journal Article↗

Measurements of iron absorption from prenatal multivitamin--mineral supplements.

Although prenatal multivitamin--mineral supplements containing 60 to 65 mg of iron, taken once daily, are used widely to assure that pregnant women absorb the approximately 3.5 mg of supplemental iron per day that they require, there have been no studies concerning the absorption of iron from these preparations. Using cross-over studies in groups of normal nonpregnant women of childbearing age, such iron absorption was assessed using a technique in which absorption is calculated from the measured increase in serum iron after the oral ingestion of iron in various forms. With each of 4 different brands of prenatal supplements, mean iron absorption was less than the required 3.5 mg and ranged from 1.8 to 3.0 mg. These values were significantly less (P less than .01) than the 8.1 mg that was absorbed from 65 mg of iron alone. Decreased iron absorption in the prenatal supplements was shown to be due to inhibition by calcium carbonate and magnesium oxide and, in some cases, to poor iron release. When one of the 4 brands was reformulated to contain less calcium carbonate and less magnesium oxide, mean iron absorption increased to 4.5 mg. It is concluded that the amount of iron absorbed from many prenatal multivitamin--mineral supplements is significantly less than with standard forms of iron in nonpregnant women and that bioavailability studies should be performed on pregnant patients to determine whether these commercial preparations provide adequate amounts of iron during pregnancy.

Absorption↗

Magnesium deficiency increases oxidative stress in rats.

Magnesium deficiency has been implicated in the development of atherosclerosis and late diabetic complications, diseases often associated with increased oxidative stress. Present study was carried out to examine the effect of magnesium deficiency on oxidative stress and total radical trapping antioxidant parameter (calculated) in rats and correlate it with the development of free radical mediated diseases. Male Wistar rats were divided into two groups and pair fed for six weeks with low magnesium diet (70 mg/kg) and control diet (990 mg/kg) prepared synthetically. Deionized water was given ad libitum. Low magnesium diet caused a significant decrease in plasma and red blood cell magnesium levels. A marked increase in plasma malondialdehyde and corresponding decrease in total radical trapping antioxidant parameters (calculated) were observed in the low magnesium diet group than control group. The level of plasma glucose increased moderately in the low magnesium diet group. Hypertriglyceridemia and significantly decreased plasma HDL (high density lipoprotein)-cholesterol levels were observed in the low magnesium diet group. The results clearly demonstrate that magnesium deficiency is associated with increased oxidative stress through reduction in plasma antioxidants and increased lipid peroxidation suggesting that the increased oxidative stress may be due to increased susceptibility of body organs to free radical injury.

Animals↗

Desorption of atropine sulphate and hyoscyamine hydrobromide by various antacids in vitro.

Desorption of atropine sulphate and hyoscyamine hydrobromide by antacids such as magnesium trisilicate, magnesium oxide, aluminium hydroxide an bismuth carbonate was carried out i vitro. This was achieved by preparing a complex of the alkaloids with bromothymolblue and then partitioning th complex between aqueous buffer phase and non-aqueous chloroform phase. The latter was analyzed colorimetrically. The desorption followed the sequence: magnesium trisilicate greater than bismuth carbonate greater than aluminium hydroxide greater than magnesium oxide. The results also show that desorption is dependent on the amount of alkaloid adsorbed and the pH of the medium.

Adsorption↗

The in vitro adsorption of some antibiotics on antacids.

The adsorption of oxytetracycline hydrochloride, tetracycline hydrochloride, doxycycline hyclate, triacetyloleandomycin, chloramphenicol, ampicillin, and cloxacillin sodium was studied on various antacids namely, magnesium trisilicate, magnesium oxide, calcium carbonate, bismuth oxycarbonate, aluminium hydroxide, and kaolin. The adsorption of the various antibiotics by milk was also tested as milk is frequently used as an antacid. Charcoal was included in the present study as a model adsorbent having a large hydrophobic surface. The adsorption of the various antibiotics on the different antacids and other adsorbents in most cases obeyed the Freundlich adsorption isotherm. Magnesium trisilicate and magnesium oxide showed the highest adsorptive capacity, relative to other antacids used, for most antibiotics. Calcium carbonate and aluminium hydroxide and intermediate power while kaolin and bismuth oxycarbonate had the least adsorptive power. Charcoal exhibited a marked adsorption for all antibiotics tested. Tetracyclines were found to be more highly adsorbed than other antibiotics studied. Triacetyloleandomycin and chloramphenicol had intermediate values. Ampicillin was only adsorbed to a slight extent while cloxacillin was not adsorbed on the antacids used. The extent of adsorption was correlated to the structure of both the adsorbent and adsorbate, the pH of the adsorbent suspension, and to the polarity of the antibiotic in such pH. The reversibility of the adsorption process was studied in different media and at pH values similar to those of the gastrointestinal tract. The extent of elution was found to be inversely proportional to the adsorptive capacity of the different adsorbents. In general, 0.0143 n NaHCO3 solution was found to possess higher eluting properties than 0.01 n HCl. An exception to this pattern was observed with tetracyclines adsorbed on aluminium hydroxide where the elution with acid resulted in a higher degree of desorption. Careful in vitro and in vivo testing of drug availability is advisable prior to the concomitant administration of antibiotics with antacids or other adsorbents.

Adsorption↗

pH-independent drug release of an extremely poorly soluble weakly acidic drug from multiparticulate extended release formulations.

Extended release mini matrix tablets for 8-Prenylnaringenin (8-PN), an extremely poorly soluble weakly acidic drug, were developed by using polyvinylacetate/polyvinylpyrrolidone as matrix former. Mini matrix tablets were manufactured by direct compression or wet granulation technique. With conventional modified release formulations, the drug demonstrated pH-dependent release due to pH-dependent solubility of the drug substance (i.e., increasing solubility at higher pH-values). In order to achieve pH-independent drug release two classes of pH-modifying agents (water-soluble vs. water-insoluble) were studied with respect to their effect on the dissolution of 8-PN. Addition of water-soluble salts of weak acids (sodium carbonate and sodium citrate) failed in order to achieve pH-independent 8-PN release. In contrast, addition of water insoluble salts of a strong base (magnesium hydroxide and magnesium oxide) was found to maintain high pH-values within the mini matrix tablets during release of 8-PN at pH 1 over a period of 10 h. The micro-environmental conditions for the dissolution of the weakly acidic drug were kept almost constant, thus resulting in pH-independent drug release. Compound release from mini matrix tablets prepared by wet granulation was faster compared to the drug release from tablets prepared by direct compression.

Calcium Phosphates↗