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Biomedical subjects

H G Classen

Publications and source records attributed to H G Classen.

At least 55 records · Page 3Linked to original sources

Prevention of stress-induced damage in experimental animals and livestock by monomagnesium-L-aspartate hydrochloride.

Monomagnesium-L-aspartate hydrochloride (Mg-Asp. HCl) is readily absorbed from the intestine of rats because this process is not saturable. Depending upon the dose administered, Mg-Asp. HCl exhibits Ca-antagonistic effects and inhibits the release of stress hormones. Higher concentrations of Mg salts, which do not contain chloride, e.g. MgO, tend to induce hypochloremic, metabolic alkalosis and changes of urinary pH, whereas MgCl2 produces hyperchloremic acidosis under these conditions. Evidence is given that oral supplementation with Mg-Asp. HCl has beneficial effects not only in experimental animals or livestock, but also in man, e.g. on exposure to muscular stress.

Acid-Base Equilibrium↗

Systemic stress, magnesium status and cardiovascular damage.

Evidence is given that cardiovascular damage due to systemic stress is potentiated by a coexisting Mg deficit. Supplementation with Mg is not only a suitable measure to eliminate this risk factor, but can also increase resistance against stressors in experimental animals, livestock and probably in man, too. When Mg is supplied in larger amounts by the oral route, care must be paid to bioavailability and acid base status.

Administration, Oral↗

Experimental data on the problem of specific hepatosplenography with radiodense lipomicrons.

Investigations into specific hepatosplenography performed with the aid of radiodense lipomicrons of different size ranges and various surface layers are presented. It is concluded that certain synthetic neutral and/or negatively charged amphiphilic substances may enhance hepatic and splenic uptake of small lipomicrons. Kinetics concerning clearance of lipid globules from the blood and hepatic concentration as well as elimination rates are studied. Furthermore, circulatory reactions following the intravenous administration of lipid emulsions and interactions between lipid globules and plasma proteins or synthetic polymeric substances are discussed.

Animals↗

[Magnesium therapy in pregnancy. Pharmacologic and toxicologic aspects of magnesium supplementation and use in pre-eclampsia and threatened premature labor].

The efficacy of parenteral Mg therapy for pre-eclampsia and eclampsia is due to the Mg antagonism of Ca ions. Accordingly, the Mg additional treatment of medicamentous tocolysis reduces the risk of an over-increased cardial energy consumption; at the same time Mg has an effect which inhibits uterine contractions. The favourable effects on the nocturnal calf cramps are due to the compensation of a combined Mg and Ca deficiency and/or a membrane stabilisation caused by Mg. In animal experiments all reproduction processes were negatively influenced by Mg deficiency, whilst the rate of abortions in early and late pregnancy as well as premature births decreased in pregnant women after administration of Mg. The perinatal mortality is similarly favourably influenced. Since prophylactic oral Mg application is effective and safe, it can be recommended without reservations.

Adrenergic beta-Agonists↗

Inhibition of nitrate-induced increase of plasma nitrite and methemoglobinemia in rats by simultaneous feeding of ascorbic acid or tocopherol.

The formation of plasma nitrite and levels of methemoglobin (MH) were studied after oral treatment with NaNO3 in female SD rats. No effects were observed when NaNO3 was administered in aqueous solution. However, feeding of diets containing an added 5% NaNO3 daily during 1 h significantly increased plasma NO2- and MH. These effects were significantly inhibited by the addition of ascorbic acid or of tocopherol to the NaNO3-containing diet. The transplacental transfer of NO2- was demonstrated as well as fetal methemoglobinemia.

Animals↗

Magnesium and potassium deprivation and supplementation in animals and man: aspects in view of intestinal absorption.

States of K and Mg deficiency, deprivation or depletion, are difficult to detect by determining serum concentrations, since both cations are concentrated intracellularly. The intestinal absorption of K is rather quick and complete; the uptake of Mg probably comprises two mechanisms and proceeds continuously, although incomplete. The resulting different pharmakokinetic behavior must be kept in mind when K and Mg are supplemented by the oral route. Favorable effects of oral K and Mg supplementation are reviewed, and the fact is stressed that the body cannot retain K, unless the Mg status is adequate. Therefore, K should be supplemented together with Mg. Drugs like amiloride not only spare K, but at the same time prevent renal losses of other important electrolytes, especially of chloride and Mg.

Administration, Oral↗

Influence of decreased and increased magnesium supply on the cardiotoxic effects of epinephrine in rats.

Female Sprague-Dawley rats kept on a standard chow or on a magnesium (Mg)-deficient diet during 6 days received s.c. injections of 0, 25, 50, 100 and 200 micrograms of epinephrine (Ep). 1 h before, they were orally treated with 0, 125 or 250 mg of Mg/kg b.w. given as magnesium aspartate hydrochloride. Drug-induced changes were studied by analyzing serum and cardiac tissue samples (Mg, Ca, K, Na and in addition glucose, FFA, cholesterol and creatine kinase in serum) taken at 7 different times (15 to 420 min) after treatment with Ep; effects were evaluated by considering the respective areas under the concentration-time curves (AUC). AUCs were calculated with linear and logarithmic graduation of the time-scale and were also transformed into logarithms. In additional experiments, animals of both diet groups were treated with Mg and Ep as described above and the hearts, excised after 420 min, were prepared for histological examination. Cardiotoxic effects induced by adrenergic overstimulation were aggravated by Mg deficiency. Most pronounced electrolyte alterations and histologically detectable cardiac necroses were observed in the Mg-deficient animals at 420 min following the s. c. injection of 200 micrograms of Ep. On the other hand, oral Mg treatment induced hypermagnesemia and reduced toxic effects of Ep--especially Ca overload of the heart muscle--in controls and in Mg-deficient rats.

Animals↗

Failure to produce hypertension in rats by chronic exposure to cadmium.

Groups of ten male and ten female Sprague-Dawley rats were exposed for 92 and 84 wk, respectively, to increasing concentrations of cadmium (as the chloride) in their drinking-water. The exposure levels of Cd used were 0, 5, 12.6 and 31.5 ppm Cd, and 5 ppm Cd plus certain trace metals. Blood pressure was measured in unanaesthetized animals at regular intervals (46 times in females, 49 times in males) by an indirect method to which the animals were kept conditioned. At the end of the experiments blood pressure was also determined directly under sodium pentobarbital anaesthesia. Although the weight of the kidneys, Cd residues and the severity of histological alterations in the kidneys increased in a dose-related manner, the blood pressure and pulse rate were not significantly affected in any of the experimental groups. There was a dose-dependent decrease in water consumption; all other parameters remained unaffected.

Animals↗

[Inhibition of stress reactions by magnesium. Beneficial effects of parenteral magnesium therapy on the development of stress ulcers in rats (author's transl)].

In rats fasted for 24 h with drinking-water ad libitum, gastric ulcers were produced by immobilization for 18 h. Subcutaneous injections of magnesium-aspartate-hydrochloride (Maganesiocard) induced pronounced hypermagnesemia after about 1, 7 and 13 h. Macroscopical estimation of gastric lesions as well as the quantitative microscopical examination performed under blind conditions and considering both surface and depth of the ulcers revealed significant protective effects of the magnesium therapy.

Animals↗

Acute toxicity testing of some herbicides-, alkaloids-, and antibiotics-metabolizing soil bacteria in the rat.

Seven strains of soil bacteria with the ability to metabolize herbicides, alkaloids or antibiotics were tested in rats for acute toxicity. 1. Upon oral administration of 9.0 x 10(8) to 6.6 x 10(10) cells daily during 7 d no adverse reactions were observed. 2. Exposure by air did not lead to specific pulmonary changes. 3. Intracutaneous injection of 7.5 x 10(6) to 1.4 x 10(8) cells did not lead to adverse skin reactions. 4. Intraperitoneal injections up to 10(8) cells per animal did not kill rats although bacteria entered blood. At higher concentrations some mortality occurred partly due to unspecific stress reactions. 5. Animal data and observations on 20 humans being exposed to these strains for 2 months up to 15 years support the view that the bacteria tested are essentially harmless for health.

Adult↗

Stress and magnesium.

The General Adaptation Syndrome is characterized by three stages: Alarm Reaction - Adaptation - Exhaustion. Results of animal experiments and clinical observations indicate that both central nervous and peripheral systemic reactions to acute stress - e.g. noise - can be accentuated by magnesium deficiency and reduced by mild hypermagnesemia, respectively. Concerning long term suboptimal magnesium supply, experimental data indicate that a stage of adaptation might be achieved during a certain period of time, preceded and followed by stages of markedly decreased resistance.U

Animals↗

Platelet aggregation evoked in vitro and in vivo by phosphatidic acids and lysoderivatives: identity with substances in aged serum (DAS).

In serum incubated at 36 degrees C for 18-24 hours a factor (DAS) develops which on intravenous injection into cats evokes platelet aggregation followed by an increase in pulmonary vascular resistance (PVR). This change in PVR is mediated via the platelets since it significantly correlates with the preinjection platelet count. There is evidence that phosphatidic acids (PA) and lysophosphatidic acids (LPA) are the active components of DAS. Investigations performed on platelet-rich plasma from man, cat, pig, dog, rabbit, guinea pig, and rat demonstrate that only human and feline platelets exposed to PA or to LPA are aggregated. Feline platelets are more sensitive to either compound than are the platelets from men; however, human platelets exhibit two exceptional properties, a) the sensitivity rapidly declines with time, b) pretreatment with subthreshold concentrations of LPA or PA induces a specific tachyphylaxis.

Adenosine Diphosphate↗

Experimental studies on the intestinal uptake of organic and inorganic magnesium and potassium compounds given alone or simultaneously.

The peroral administration of magnesium and potassium compounds in effective doses (ED50) to rats yielded the following results: 1. Magnesium or potassium given as chlorides are significantly better absorbed than the corresponding aspartates. 2. In the presence of aspartate in higher concentrations the absorption of both magnesium and potassium is inhibited to a certain degree. 3. Increasing amounts of chloride cannot abolish the inhibitory effect of aspartate on potassium absorption, in contrast magnesium, which, in the presence of aspartate is better taken up when chloride is provided. 4. High concentrations of magnesium may perhaps impede the uptake of potassium to a small degree but not vice versa. 5. Magnesium losses from the body--induced by treatment with 9-alpha-fluorocortisol-acetate--can be effectively substituted by peroral administration of chloride-containing magnesium compounds over a reasonable time. The simultaneously occurring loss of potassium cannot be corrected correspondingly by potassium supplements.

Animals↗

[N-Methylphenethylamine, an indirect sympathicomimetic agent in vegetables (author's transl)].

N-Methylphenethylamine, a secondary amine present in vegetable foodstuffs, in concentrations up to 6.6 ppm, is an indirectly acting sympathomimetic amine; on i.v. injection the circulatory effects correspond to 1/80 to 1/100 of those of epinephrine. Following enternal application pressoric and positive chronotropic effects are observed during appr. 30 min; the no-effect level amounts to about 7 mg/kg.

Animals↗

Magnesium concentrations in plasma and bone following enteral administration of Br-, Cl- and Mg++ in the form of different compounds and combinations.

In accordance with the results achieved in previous experiments the intestinal absorption of magnesium and its uptake into bone of rats were significantly improved when MgCl2 or mono-magnesium-mono-aspartate-hydrochloride (Mg asp. HCl) were used instead of mono-magnesium-di-l-aspartate (Mg asp.). Treatment with mono-magnesium-mono-aspartate-hydrobromide (Mg asp. HBr) resulted in remarkably elevated magnesium concentrations in plasma and bone. Since the animals were strongly sedated at the same time, we had to differentiate the influence of anesthesia from unspecific distress and specific actions of bromide and chloride, e.g. on intestinal uptake and/or renal excretion of Mg. Experiments in which the narcotic effect of bromide was reduced to moderate sedation by additional treatment with chloride would appear to suggest that both specific and unspecific mechanisms were involved. In additional experiments it was shown that the effects of Mg asp. plus KBr or Mg asp. plus KCl or CaCl2 were similar to those of the corresponding magnesium aspartate hydrohalogenides.

Administration, Oral↗

[Pharmacology and pharmacokinetics of magnesium (author's transl)].

A dose-dependent fall in diastolic blood pressure, pulse rate, systolic pressure, inhibition of neuromuscular transmission and blockade of sympathetic ganglia could be demonstrated during infusion of magnesium in animal experiments. In sighting trials in two clinically healthy subjects, suggestions of a phasic course for plasma Mg were found, with a minimum in the morning. After administration of magnesium asparate hydrochloride in enteric coated capsules, the plasma Mg rose, depending on the dose, with a maximum at 3.7 hours. Raising the plasma Mg over 24 hours is possible with a total dose of 9 mg/kg Mg, divided into two or three doses daily. For reasons of absorption and better tolerance, division into three doses seems more advantageous.

Adult↗