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Biomedical subjects

T Daldrup

Publications and source records attributed to T Daldrup.

At least 37 records · Page 2Linked to original sources

Influence of chronic alcohol consumption on hepatic heme and porphyrin metabolism.

To study the effect of prolonged alcohol consumption on hepatic heme and porphyrin metabolism, female Wistar rats were fed for 60 days a nutritionally adequate liquid diet containing 36% of total calories as ethanol, whereas the control diet was isocaloric and contained no alcohol. Compared to pair-fed controls, the administration of the alcohol diet resulted in an increased hepatic activity of delta-aminolevulinic acid synthase by 223% (112.3 +/- 19.6 nmoles/hr/100 g b.wt. vs. 362.8 +/- 42.5; P less than 0.01), an enhanced urinary excretion of delta-aminolevulinic acid by 101% (64.8 +/- 11.8 nmoles/day vs. 130.8 +/- 22.4; P less than 0.05), and an augmented urinary output of total porphyrins by 142% (1.2 +/- 0.2 nmoles/day vs. 2.9 +/- 0.5; P less than 0.05). Concomitantly, the hepatic content of cytochrome P-450 was significantly enhanced and that of hepatic catalase activity marginally increased, whereas the hepatic iron content remained unaltered. In summary, the feeding of rats with a liquid alcohol diet for 60 days results in changes of hepatic heme and porphyrin metabolism which are associated and may be causally related with an induction of hepatic hemoproteins and subsequent derepression of hepatic delta-aminolevulinic acid synthase, whereas hepatic iron appears to play no pathogenic role.

5-Aminolevulinate Synthetase↗

Detection of digoxin, digitoxin, their cardioactive metabolites and derivatives by high-performance liquid chromatography and high-performance liquid chromatography-radioimmunoassay.

High-performance liquid chromatographic (HPLC) systems are described for the separation of the cardioactive metabolites of the digoxin and digitoxin series that are formed by the splitting of digitoxose sugar residues from the aglycone steroid: isocratic separation of digoxin and its cardioactive metabolites; isocratic separation of digitoxin and its cardioactive metabolites; and gradient elution separation of the digoxin and digitoxin series including beta-acetyl- and beta-methyldigoxin. Separations were performed on a 10-microns bonded octadecyl phase column using various mixtures of acetonitrile--water and acetonitrile--methanol--water as the mobile phase. These methods provide high peak resolution and are well suited for collecting elution fractions, e.g. to link up with sensitive immunological measurements. An HPLC-radioimmunoassay method is described for the quantitation of digoxin, digitoxin and their metabolites in human tissues.

Chromatography, High Pressure Liquid↗

[Etryptamine, a new designer drug with a fatal effect].

Capsules with etryptamine have been commonly available on the market since the middle of 1985. Up to 1962 this CNS-stimulating, monoamine-oxidase-inhibiting drug was sold as an antidepressant (Monase). A case of fatal intoxication is reported. The exact amount of etryptamine taken several hours before death are not known, but it could have been in the range of 700 mg. This drug was detected in tissue by means of common analytical techniques (GLC, GC-MS, HPLC, TLC). Etryptamine cross-reacts with the Emit-st amphetamine assay and can also be detected in urine using these techniques. The level in postmortem blood was 1.1 mg/l. The effects the young man showed were like those known from intoxication with amphetamines, MAO inhibitors, and thymoleptics. Malignant hyperthermia is discussed as a possible cause of death. It is suggested that trade in etryptamine should be controlled.

Adult↗

[Distribution of digoxin, digitoxin and their cardioactive metabolites in human heart and kidney tissue. A postmortem study].

A method was developed for the specific determination of digoxin and digitoxin, as well as their semisynthetic derivatives and dependent cardioactive metabolites, in autopsy samples of heart and kidney. A collective of six patients on long-term treatment with therapeutic doses of beta-acetyldigoxin had a mean myocardial digoxin content of 46.1 +/- 25.0 ng/g (SD); kidney: 50.3 +/- 30.3 ng/g. Digoxigenin bisdigitoxoside represented the second most important metabolite in heart and kidney; digoxigenin monodigitoxoside and digoxigenin follow, respectively. In a collective of seven patients on maintenance treatment with digitoxin, the mean tissue levels were higher but the metabolic pattern was similar (myocardial digitoxin content: 78.9 +/- 38.4 ng/g, renal content: 104.1 +/- 44.1 ng/g). The amount of digoxin formed by hydroxylation under long-term treatment with digitoxin in heart and kidney were approximately 10 ng/g. A case of digoxin intoxication differed both in the tissue content and in the metabolic distribution.

Adult↗

[The value of the Emit-dau system in the examination of cadaveric urine].

Randomly taken postmortem urine samples (170) were analyzed by the Emit-dau system for their barbiturate and benzodiazepine content. Of the samples, 23% and 25% were found positive for barbiturate and benzodiazepine, respectively. The percentages of the positive samples were reduced by a heating process to 9% and 11%, respectively. TLC and Emit-st were used for reference procedures. The relative high percentage (above 30%) of the urine samples analyzed exhibited elevated lysozyme activity and protein value. It was found that the disturbing proteins in the Emit-dau system contained not only endogene lysozyme but other thermolabile fractions with higher molecular weight.

Barbiturates↗

[Significance of the putrefactive bacterium Clostridium sordellii for the determination of age of the cadaver].

The method of determining postmortal interval by means of the content of ABU, GABA and GLU in putrefied postmortem brain is based on the speed of spreading, the metabolism and the growth of certain clostridia. The experiments have shown that the fecal bacteria can reach the brain in a few days. The significance of this temperature-dependent invasion ability of the bacteria for the determination of the age of the corpse is discussed.

Amino Acids↗

[Degradation of glutamic acid and proline in Clostridium sordellii under cadaveric bacteriological inspection].

Glutamic acid (GLU) is decarboxylated to gamma-aminobutyric acid (GABA) by Clostridium sordellii isolated from a decaying human brain. The dependence of this reaction on temperature, pH and substrate concentration has been established. The pH-optimum is in the range of 5.0 to 5.2. Near optimal pH the temperature optimum is greater than 28 degrees C. At higher pH-values (6 to 7) activity is relatively independent of temperature. The similarity to results in decaying human brains (10, 11, 12) shows a good correlation between postmortem bacterial flora and GLU-degradation. Furthermore it is shown that C. sordellii produces delta-aminovaleric acid (AVA) from proline (PRO).

Amino Acids↗

[Formation of alpha-aminobutyric acid in Clostridium sordellii].

After a modified growth C. sordellii is able to ferment threonine as mono-substrate. It could be demonstrated for the first time that alpha-aminobutyric acid is definitely formed from threonine by clostridia. The pH-optimum of this reaction is greater than 8, the temperature optimum is greater than 28 degrees C. Further fermenting products are: glycine and presumably acetaldehyde.

Acetaldehyde↗

[Practical experiences with the determination of cadaver age by evaluation of bacterial metabolic products].

In an experiment a corpse had been kept at room temperature (16 degrees-23 degrees C) for 1163 h. At regular intervals brain samples were taken and the content of free amino acids and related compounds was determined by column chromatography. It could be demonstrated that in a period of 4-20 days postmortem the age of the corpse could be calculated from the concentrations of alpha-aminobutyrate (ABU), gamma-aminobutyrate (GABA), and glutamic acid (GLU) in brain employing the previously [5] presented formula: (formula; see text) T is the postmortem time lapse (days). ABU, GABA, and GLU are the concentrations (mumol/g) wet tissue of the corresponding amino acids. During this postmortem interval there is nearly a linear correlation; from this interval a correct assignment between concentrations and time cannot be given. The determination method is in the range of about 15 degrees-25 degrees C (guarantees bacterial growth and metabolism) independent of ambient temperature. The brain samples (cortex or parts of the putrified brain mush) can be taken without any special precaution during normal autopsy. The results of the experiment (in Fig. 1) were supported by some practical cases where the time lapse since death was well (in Fig. 1) or reasonably (in Fig. 1) known. These results suggest that this method allows in many cases the determination of the age of a corpse found in a warm environment (approximately 15 degrees-25 degrees C) approximately 4-20 days after death.

Age Factors↗

[The kinetics of the postmortal bacterial metabolism of the glutamic acid in brain (author's transl)].

This paper gives a brief report on investigations on bacterial enzyme activities in putrefied brain tissue. The effects of temperature changes (5--30 degrees C) and pH-changes (3--8) on the rate of the glutamic acid reactions, especially proteolysis and alpha- resp. gamma-decarboxylation, were examined to reveal to which extent a temperature and pH-independence is valid for the previously developed time of death formula: (formula: see text). The present investigation demonstrates the independence of the mentioned formula for the important pH-range of 6--7.2 and for a temperature range of 17.5--25 degrees C (room temperature). A second important result is that in these ranges a high proteolytic activity is observed so that the continuation of the reaction sequences will be maintained. These results reveal that the postmortal metabolism of the glutamic acid may be suitable to determine the time of death.

Aminobutyrates↗