Magnetic structure and spin reorientation of quaternary Dy2Fe2Si2C.

We have investigated the low temperature magnetic properties of Dy2Fe2Si2C by using magnetisation, specific heat, x-ray diffraction, neutron powder diffraction and 57Fe Mössbauer spectroscopy measurements over the temperature range 1.5 K-300 K. Dy2Fe2Si2C exhibits two magnetic transitions at low temperatures: an antiferromagnetic transition at [Formula: see text] K and a spin-reorientation transition at [Formula: see text] K. The magnetic structure above T t can be described with a propagation vector [Formula: see text] with the ordering of the Dy magnetic moments along the monoclinic b-axis whereas on cooling below T t the Dy moment tips away from the b-axis towards the ac-plane. We find that the spin-reorientation in Dy2Fe2Si2C is mainly driven by the competition between the second-order crystal field term B 20 and the higher-order terms, in particular B 40 and B 64.

Determination of the magnetic structure of Gd2Fe2Si2C by Mössbauer spectroscopy and neutron diffraction.

We have determined the magnetic structure of the intermetallic compound Gd2Fe2Si2C using neutron powder diffraction, (155)Gd and (57)Fe Mössbauer spectroscopy. This compound crystallizes in a monoclinic (C2/m) structure and its magnetic structure is characterized by antiferromagnetic order of the Gd sublattice along the b-axis, with cell-doubling along the c-axis. The propagation vector is k = [0 0 ½]. At 3.6 K the Gd moment reaches 6.2(2) µ(B). Finally, (57)Fe Mössbauer spectroscopy shows no evidence of magnetic ordering of the Fe sublattice.

[Therapy of cardiac arrhythmias. Clinical significance of potassium- and magnesium aspartate in arrhythmias]. / Therapie von Herzrhythmusstörungen. Die klinische Bedeutung von Kalium- und Magnesiumaspartat bei Arrhythmien.

UNLABELLED: Potassium and magnesium deficiencies usually coexist and represent a risk factor for cardiac arrhythmias. Serum levels--in particular of magnesium--are inconclusive for establishing a possible electrolyte deficiency. Basic treatment of arrhythmia should therefore include the administration of potassium and magnesium, since the benefit is great, and the possible side effects is negligible. A placebo-controlled study involving patients with cardiac arrhythmias revealed that appreciably fewer ventricular asystoles occurred after three weeks of treatment with potassium and magnesium aspartate, even when serum levels were within the normal range prior to initiating treatment. Patients older than 50, and those with previous coronary heart disease and/or myocardial infarction derived particular benefit from this form of treatment. CONCLUSION: These results underscore the key role played by potassium and magnesium in the treatment of cardiac arrhythmias.

Thiazolidine derivatives as source of free L-cysteine in rat tissue.

The present study demonstrates that a variety of thiazolidine-4-(R)-carboxylic acids (TDs) which are the products of reactions of L-cysteine (cys) with carbonyl compounds could serve as a "delivery" system for cys to the cell. Liberation of the amino acid can occur enzymatically as well as non-enzymatically. The two possibilities have been proven by identification of representative compounds. The most specific substrate for mitochondrial enzymatic oxidation was thiazolidine-4-carboxylic acid (CF), the product of the reaction of cys with formaldehyde, and the least metabolized TD was 2-methyl-thiazolidine-4-carboxylic acid (CA), the product of the reaction of cys with acetaldehyde. TDs formed from cys and different sugars were not metabolized at all in mitochondria. N-Formyl-L-cysteine (NFC) the intermediate product of mitochondrial metabolism of CF was ascertained by 1H-NMR spectroscopy whereas N-acetyl-L-cysteine (NAC), the predicted metabolite of CA, was not detected, possibly due to a fast turnover. The further enzymatic hydrolysis of NFC as well as NAC to free cys was demonstrated to take place in the cytoplasm. Non-enzymatic hydrolysis of TDs depended on the chemical nature of the substituents in the thiazolidine (Th) ring. The most stable compound was unsubstituted Th and the least stable were CGlu(D) and CA. Following non-enzymatic ring opening and hydrolysis, CA was converted to methyl-djenkolic acid, which equilibrates with CA. We have identified this new compound by 1H-NMR spectroscopy. TDs may cause both a decrease and an increase in the levels of SH-groups in mitochondria. In the case of the stable CF, which is metabolized only enzymatically, an increase in the levels of SH-groups in mitochondria was observed. This suggests that enzymatic control of the breakdown of TDs prevents overflowing of the cell with thiol groups. The latter seems to be induced by high concentrations of those TDs which are hydrolysed non-enzymatically. This process leads finally to a decrease in free SH-groups by different mechanisms. The findings demonstrate two different mechanisms by which TDs can provide cys to the cells. The biological and pharmacological consequences are discussed.

Beta-carbolines and tetrahydroisoquinolines: detection and function in mammals.

beta-Carbolines occur in man and rat. The concentration in various tissues is about 100 to 1000 times lower than that of classical neurotransmitters. Administration of beta-carbolines in animals induces overlapping but not identical activity profiles. The molecular modes of action differ. For example, harman (1-methyl-beta-carboline) acts as an endogenous inhibitor of monoamine oxidase [E.C. 1.4.3.4.], subtype A, whereas norharman (beta-carboline) probably acts by stimulation of a specific beta-carboline receptor which is different from the benzodiazepine-GABA receptor complex. There is substantial evidence that tetrahydroisoquinolines occur under physiological conditions as well. Whether tetrahydropapaveroline serves as a precursor of morphinanes in mammals, as has been found in opium poppies, remains to be elucidated.

beta-Carbolines and Tetrahydroisoquinolines: Detection and Function in Mammals.

beta-Carbolines occur in man and rat. The concentration in various tissues is about 100 to 1000 times lower than that of classical neurotransmitters. Administration of beta-carbolines in animals induces overlapping but not identical activity profiles. The molecular modes of action differ. For example, harman (1-methyl-beta-carboline) acts as an endogenous inhibitor of monoamine oxidase [E.C. 1.4.3.4.], subtype A, whereas norharman (beta-carboline) probably acts by stimulation of a specific beta-carboline receptor which is different from the benzodiazepine-GABA receptor complex. There is substantial evidence that tetrahydroisoquinolines occur under physiological conditions as well. Whether tetrahydropapaveroline serves as a precursor of morphinanes in mammals, as has been found in opium poppies, remains to be elucidated.

Formation of thiazolidine-4-carboxylic acid represents a main metabolic pathway of 5-hydroxytryptamine in rat brain.

Incubation of 5-hydroxytryptamine (5-HT) with rat brain homogenate resulted in the formation of (4R)-2-[3'-(5'-hydroxyindolyl)-methyl]-1,3-thiazolidine-4-carboxyl ic acid (5'-HITCA) as the major metabolite. The substance represents the condensation product of 5-hydroxyindole-3-acetaldehyde with L-cysteine. The chemical structure was confirmed by chromatographic and chemical methods as well as by fast atom bombardment mass spectrometry. Incubation of 5-HT in the presence of L-cysteine yielded the thiazolidine as the main metabolite up to 4 h. Under these conditions, the concentration of 5-hydroxyindole-3-acetic acid (5-HIAA) amounted to about 20% and 57% of 5'-HITCA (0.5 h and 4 h, respectively). In contrast to these findings, indole-3-acetic acid (IAA) was identified as the major metabolite when tryptamine was incubated under similar conditions. (4R)-2-(3'-Indolylmethyl)-1,3-thiazolidine-4-carboxylic acid (ITCA) was found to be the main conversion product of tryptamine only during the first 30 min. To investigate the fate of the thiazolidines, radiolabelled and unlabelled ITCA was incubated with rat brain homogenate. The compound was degraded enzymatically and rapidly. Subcellular fractionation revealed that the enzyme activity was present mainly in the cytosolic fraction whereas the preparation of mitochondria showed less activity. The responsible enzyme is presumably a carbon-sulfur lyase (EC 4.4.1.-). The major metabolite was isolated by HPLC and identified by mass spectrometry as well as by comparison with reference compounds to be IAA.(ABSTRACT TRUNCATED AT 250 WORDS)

Formation of a new biogenic aldehyde adduct by incubation of tryptamine with rat brain tissue.

Tryptamine was degraded by incubation with rat brain homogenate to an unknown product. The reaction was stimulated by the nonionic detergents Triton X-100 and Lubrol PX and less by the zwitterionic detergent 3-[(3-cholamidopropyl)dimethylammonio]1-propanesulfonate (CHAPS). The same results were obtained with pig brain and bovine brain. The monoamine oxidase inhibitor pargyline inhibited the reaction strongly, indicating the participation of the enzyme on the reaction. Addition of 17,000 g supernatant from rat brain homogenate increased the formation effectively whereas phospholipids or chloroform/methanol (7:3) extract from the 17,000 g supernatant showed only little or no effect. Chromatographic and electrophoretic properties as well as the chemical reaction of the product with specific reagents suggest that the compound consists of an indole part and an amino acid part. The product could be identified by fast atom bombardment mass spectrometry and by comparison with the synthetic substance (4R)-2-(3-indolylmethyl)-1,3-thiazolidine-4-carboxylic acid. It is formed by the enzymatic oxidation of tryptamine producing indole-3-acetaldehyde which spontaneously cyclizes with free L-cysteine from the tissue. The results suggest that the reaction of biogenic aldehydes with brain macromolecules may proceed via an analogous reaction.

Formation of 1-methyl-beta-carbolines in rats from their possible carboxylic acid precursor.

In vivo metabolism of 1-methyl-1,2,3,4-tetrahydro-beta-carboline-1-carboxylic acid (1-CTHH), a possible precursor of the endogenous beta-carbolines tetrahydro-harman (THH) and harman was investigated in rats. Following intraperitoneal injection of [4-14C]1-CTHH, a rapid distribution of the radioactivity in the tissues was observed. The highest radioactivity was measured in the kidney and the lowest in the brain as well as in the fat tissue. Approximately 55% of the administered dose was excreted in the urine within 90 min. The radioactivity in the urine consisted of unchanged 1-CTHH (greater than 90%) besides harmalan and trace amounts of harman. Harmalan represents the major degradation product of 1-CTHH; it could be identified in all tissues examined and in the urine. The concentration in the blood, however, was low at all time points investigated. The peak concentration of harmalan in most tissues was measured between 15-30 min after injection. A time-dependent formation of THH was found in the lung and spleen indicating an important role of these organs in the biosynthesis of THH. Furthermore, the metabolism of [4-14C]1-CTHH in the brain was studied following intracerebroventricular injection. The formation of harmalan in the brain was not affected by pretreatment with the aromatic amino acid decarboxylase inhibitor NSD 1015. Determination of the harmalan concentration in several brain regions revealed a high level in the hippocampus and hypothalamus and a small concentration in pons, corpus striatum, cerebellum and cerebral cortex 20 min after injection. The analyses of the

Degradation of tryptamine in pig brain: identification of a new condensation product.

Incubation of tryptamine with pig brain homogenate led to the formation of a product which is not identical with other known tryptamine metabolites. The same results were observed with rat brain tissue and bovine brain tissue. The compound has been isolated and identified by NMR spectroscopy, fast atom bombardment mass spectroscopy, and by chemical synthesis as a thiazolidine derivative, (4R)-2-(3-indolylmethyl)-1,3-thiazolidine-4-carboxylic acid. It is formed by a condensation reaction of indole-3-acetaldehyde generated enzymatically from tryptamine and of free L-cysteine present in the tissue. The compound inhibited monoamine oxidase (preferentially type A) and the neuronal gamma-aminobutyric acid uptake.

Biotransformation of 1-methyl-1,2,3,4-tetrahydro-beta-carboline-1-carboxylic acid to harmalan, tetrahydroharman and harman in rats.

1-Methyl-1,2,3,4-tetrahydro-beta-carboline-1-carboxylic acid (1-carboxytetrahydroharman, 1-CTHH) has been detected in the brain of rats following intracerebroventricular injection of tryptamine and pyruvic acid. We now report the metabolism of this compound. Following intraperitoneal injection of 1-CTHH into rats, harmalan was found to be the major metabolite besides tetrahydroharman (THH) and harman. A high concentration of THH was measured in the lung while most of harman was found in the urine. Harmalan and THH could be detected in the brain in low concentrations. The products were separated following extraction from tissues by high-performance liquid chromatography (HPLC) on a reversed phase C18-DB column. The identity of the metabolites was confirmed by mass spectrometry (MS) analysis. The results demonstrate the role of 1-CTHH as a precursor of the biologically active compounds harmalan, THH and harman.

Formation of a beta-carboline (1,2,3,4-tetrahydro-1-methyl-beta-carboline-1-carboxylic acid) following intracerebroventricular injection of tryptamine and pyruvic acid.

Tritium labelled 1-carboxy-tetrahydroharman was identified in rat brain following i.c.v.-injection of [3H]tryptamine and pyruvic acid. The animals had been treated with the MAO inhibitor pargyline (40 mg/kg) 30 min before i.c.v. injection. Under these conditions, only trace amounts of [3H]indole acetic acid could be detected in the brain. The formation of 1-CTHH was time-dependent. Five minutes following the i.c.v. injection, approximately 0.45% of the administered tryptamine was converted into 1-CTHH and 23% were still unchanged. The amount of the radioactive 1-CTHH increased slightly within 1 h (0.8%; [3H] tryptamine: 6%). Pretreatment of the rats with high doses of pargyline (75 mg/kg; 90 min before i.c.v. injection) prevented the formation of both [3H]1-CTHH and [3H]indole acetic acid (IAA) suggesting that high doses of pargyline inhibit the formation of 1-CTHH. As control for a possible non-enzymatic formation of 1-CTHH, [3H]tryptamine and various concentrations of pyruvic acid were incubated in phosphate buffer at pH 7.4. 1-CTHH was not detected under these conditions. However, the formation of 1-CTHH was observed at high pyruvic acid concentrations (final concentration = 100 mM) and low pH values (less than pH4). To support the assumption that the observed condensation of both precursors to 1-CTHH occurred intracellularly, the metabolism of tryptamine was studied. Two minutes after i.c.v. injection of [3H]tryptamine approximately 4% of the injected dose remained unchanged and 10% were metabolized to [3H]IAA. These findings suggest a rapid disappearance of [3H]tryptamine from the cerebrospinal fluid as well as a rapid penetration into the cerebral tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Pharmacology of harmalan (1-methyl-3,4-dihydro-beta-carboline).

Harmalan is presumably formed in vivo as an intermediate product of the biosynthesis of harman as well as tetrahydroharman. The pharmacological effects of harmalan as well as its affinity towards benzodiazepine, 5-HT2 and tryptamine binding sites were investigated in the present study. Harmalan induced clonic convulsions which were antagonized by diazepam. Receptor binding experiments as well as combined treatments with antagonists point to an interaction which involves neither benzodiazepine nor 5HT2 receptor sites but rather tryptamine binding sites. Good agreement was found between the potency of harmalan to increase spontaneous motor activity and the affinity to the tryptamine binding sites when compared with the effects of tryptamine in both tests. In the light-dark-chamber test for predicting anxiolytic effects of drugs, harmalan elicited opposite effects to diazepam. The results of combined treatment also suggested an interaction of both compounds not involving benzodiazepine receptors. Tryptamine binding sites seemed to play no role since the amine was inactive under these conditions. Thus, harmalan induces several tryptamine agonistic effects and others not involving tryptamine binding sites.