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Biomedical subjects

A Schmoldt

Publications and source records attributed to A Schmoldt.

At least 37 records · Page 2Linked to original sources
PubMed1996

Three suicide attempts with moclobemide.

OBJECTIVE: To report plasma moclobemide, course and outcome of two cases of overdose with moclobemide alone and one case of combined ingestion of moclobemide and clomipramide. METHODS: Moclobemide identification and quantification was achieved by gas chromatography-mass spectrometry after alkaline extraction. CASE REPORTS: In case 1, plasma moclobemide was 2.8 mg/L with 1.8 mg/L clomipramide; in case 2, 18 mg/L; in case 3 60.9 mg/L and 4.6 mg/L 12 hours later. None of the patients showed serious effects during 24 hours of observation. Plasma moclobemide at 10 to 30 times therapeutic was not associated with major toxic effects. Moclobemide seems to be considerably less toxic than tricyclic antidepressants.

Antidepressive Agents, Tricyclic↗
PubMed1995

[Fatal vacuolar cardiomyopathy in chronic chloroquine drug treatment].

Clinical and morphological findings recorded in an 81-year-old woman patient with a 45-year history of rheumatoid arthritis treated with long-term chloroquine therapy are reported. The cause of death was low cardiac output syndrome, which upon autopsy and postmortem toxicological analyses was classified as vacuolar chloroquine-induced cardiomyopathy. The pathogenesis and the morphological and clinical characteristics of cardiotoxic effects of chloroquine are reviewed.

Aged↗
PubMed1994

[A compilation of therapeutic and toxic plasma drug concentrations].

In order to assess the significance of drug levels measured in clinical and forensic toxicology as well as for therapeutic drug monitoring (TDM), it is essential that good collections of data are readily available. For more than 400 frequently used drugs therapeutic and, if data were available, toxic and fatal plasma concentrations as well as elimination half-lives were compiled in a table including, e.g., hypnotics like barbiturates and benzodiazepines, neuroleptics, antidepressants, sedatives, analgesics, anti-inflammatory agents, antihistamines, anti-epileptics, beta-adrenergic antagonists, antibiotics (penicillins, cephalosporins, aminoglycosides, gyrase inhibitors), diuretics, calcium-channel blockers, cardiac glycosides, anti-arrhythmics, anti-asthmatics, angiotensin converting enzyme inhibitors, opioid agonists, and local anaesthetics. Data have been abstracted from published information, both compilations and primary sources, and supplemented with data collected in our own forensic and clinical toxicology laboratories. Wherever possible, ranges for therapeutic plasma concentrations are expressed as trough concentration at steady-state. The range of (or single) half-life values given for each drug are chosen to represent the terminal log-linear phase at most. In addition to the assessment of significance of drug levels for the therapeutic monitoring of patients, this list can assist the diagnostic assessment in cases of intoxication.

Drug Therapy↗
PubMed1994

Successful physostigmine treatment of acute dothiepin intoxication.

We report on a severe intoxication with the tricyclic antidepressant dothiepin. A treatment with a continuous infusion of physostigmine was successful and improved the ventricular arrhythmia. Dothiepin and its active metabolites were determined in plasma and urine by HPLC.

Adult↗
PubMed1993

Undetected drug addict fatalities.

A urine screening in fatalities with an unnatural or unknown cause of death (13-40 years of age) was carried out to evaluate the proportion of undetected drug-related cases. Ten out of 160 fatalities without a hint of drug consumption were classified as drug-related according to the definition of the Bundeskriminalamt; 5 of them committed suicide. Moreover, we found a relevant amount of AIDS deaths from the risk group of intravenous drug addicts not registered as drug-related deaths.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Comparison of drug abuse fatalities and emergencies.

During a 9-month period, drug abuse emergencies were investigated prospectively and compared with drug-related fatalities of the same period. The emergency patients were of younger age, the proportion of women and the prevalence of infections with HIV, HBV and HCV was higher than in drug-related deaths. Additional alcohol consumption was similar in both groups but more frequent in drug-addict emergencies where the patients were 20-30 years of age. It is suggested that the emergency patients might characterise a special risk group of drug addicts and might be a target for interventional help to prevent fatalities.

Adolescent↗
PubMed1993

Differential effects of misoprostol and ranitidine on the pharmacokinetics of diclofenac and gastrointestinal symptoms.

1. The effects of oral misoprostol (800 microg day(-1)) and ranitidine (300 mg day(-1)) on the pharmacokinetics of diclofenac (100 mg) were assessed in a three-way randomized crossover study in 18 healthy male subjects. 2. Subjects were studied over three 8 day periods, during which they received twice-daily placebo, misoprostol, or ranitidine. A single dose of diclofenac was given orally on days 1 and 8, and plasma diclofenac concentrations were measured by h.p.l.c. over 24 h. 3. Misoprostol caused a non-significant 19% increase in the mean Cmax value of diclofenac on both days 1 and 8. After 8 days of dosing with misoprostol there was a significant (P = 0.04) 20% decrease in the AUC of diclofenac. 4. Ranitidine had no statistically significant effects on the pharmacokinetics of diclofenac. 5. Co-administration of misoprostol and diclofenac was associated with a higher frequency and severity of gastrointestinal symptoms and frequency of bowel opening, and a decrease in faecal consistency when compared with either placebo or ranitidine plus diclofenac (P < 0.01).

Administration, Oral↗
PubMed1992

Monoclonal antibodies against 4-hydroxybiphenyl-UDP-glucuronosyltransferase.

Monoclonal antibodies against purified rat liver 4-hydroxybiphenyl UDP-glucuronosyltransferase were developed using the hybridoma technology. In immunoblot analysis the antibodies specifically reacted with purified 4-hydroxybiphenyl-UDPGT but not with other purified UDPGT enzyme fractions. One single band was detected with microsomes of rat liver and small intestine but not with microsomes of kidney and lung. The reactive protein was also found in dog and human liver microsomes. It could be shown that there was no increase of immunoreactive protein after pretreatment with phenobarbital or 5,6-benzoflavone. This supports the hypothesis that more than one 4-hydroxybiphenyl-UDPGT exist in rat liver which are differently inducible.

Animals↗
PubMed1992

Hydroxysteroid sulfotransferase and a specific UDP-glucuronosyltransferase are involved in the metabolism of digitoxin in man.

In vitro experiments were performed with cytosolic and microsomal fractions of human liver specimens in order to investigate which enzyme forms of sulfotransferase (ST) and UDP-glucurosyltransferase (GT) are involved in the metabolism of digitoxin (dt-3) and/or its cleavage products. It was found that the cytosolic STs preferentially react with digitoxigenin (dt-0) whereas microsomal GTs conjugate digitoxigenin-monodigitoxoside (dt-1) and in traces the bisdigitoxoside (dt-2). Dt-3 and dt-0 cannot be glucuronidated. By separation of different sulfotransferases it was found that the hydroxysteroid-ST is responsible for dt-0 and 3-epidigitoxigenin (epi-dt-0) sulfation. The hydroxysteroid-ST could be purified and characterized (apparent Km and Vmax for dt-0 sulfation: approx. 17 mumol/l and 2.7 nmol/min mg protein, respectively). Of various model substrates and endogenous compounds (steroids, bilirubin) none caused a competitive inhibition of the microsomal dt-1 glucuronidation except dt-2 and dt-3. Therefore it can be supposed that a new GT form catalyses this reaction. It is characterized by an extraordinarily high affinity towards dt-1 with Km values ranging between 0.7 and 27 mumol/l.

Binding, Competitive↗
PubMed1991

Rat liver microsomal ring- and S-oxidation of thiaarenes with central or peripheral thiophene rings.

The metabolism of the following thiaarenes has been investigated using liver microsomes of untreated, phenobarbital-, AroclorR- and 5,6-benzoflavone-pretreated rats: dibenzothiophene, naphtho[2,1-b]thiophene, benzo[b]naphtho[2,1-b]thiophene, benzo[b]naphtho[1,2-d]thiophene, benzo[b]naphtho-[2,3-d] thiophene, phenanthrol[1,2-b]thiophene, phenanthrol[4,5-bcd] thiophene, triphenyleno[1,12-bcd]-thiophene and dinaphtho[2,1-b:1',2'-d]thiophene. Thiaarenes with a central thiophene ring preferentially undergo S-oxidation and are converted into sulfoxides and sulfones, whereas those with a peripheral thiophene ring are oxidized at the carbocyclic skeleton resulting in the formation of phenols, dihydrodiols and triols. Sulfone formation seems to be inducible by phenobarbital but only little or not by 5,6-benzoflavone treatment. In most cases 5,6-benzoflavone and AroclorR treatment enhanced the rates of ring oxidation.

Animals↗
PubMed1991

[Therapeutic and toxic plasma concentrations and elimination half-lives of commonly used drugs].

For 253 frequently used drugs therapeutic and, if data were available, toxic, and fatal plasma concentrations as well as elimination half-lives were compiled in a table. To assess the significance of drug levels for the therapeutic monitoring of patients, it is essential that a collection of data is readily available. In addition, this list can assist the diagnostic assessment in case of intoxications.

Drug Therapy↗
PubMed1991

[Increase in paracetamol poisoning].

During the last 5 years a continuous increase of the number of intoxications with the analgesic paracetamol has been realized. Most cases were due to attempted suicides whereas few cases resulted from accidental overdosing to small children. In the latter case two to threefold overdoses often caused serious intoxications. Whereas the number of attempted suicides with other drugs remained constant only those with paracetamol increased. In contrast to attempted suicides with other drugs people below 20 years form the major group of those taking paracetamol.

Acetaminophen↗
PubMed1990

Induction of rat liver microsomal cytochrome P-450 by the pentabromo diphenyl ether Bromkal 70 and half-lives of its components in the adipose tissue.

Pentabromo diphenyl ether (Bromkal 70) was investigated for its half-life in perirenal fat of male and female Wistar rats following a single 300 mg/kg p.o. dose. Half-lives of five individual component fractions following extraction and separation with HPLC were between 30 and 91 days in female rats and between 19 and 119 days in male rats. Induction experiments in male and female Wistar rats with long-term (50 mg/kg daily for 28 days) and short-term administration (300 mg/kg once or 100 mg/kg daily for 4 days) resulted in a 2.3-3.9-fold increase of the cytochrome P-450c, an up to 2-fold increase of benzphetamine N-demethylation activity, a 2.2-5.3-fold increase of the benzo[a]pyrene oxidation activity, and an increase of the ethoxyresorufin O-deethylation activity to between 4.1 and 16.6 nmol/min mg microsomal protein. All variations of enzymatic activities were dependent on the animals' sex or on the administration schedule of the pentabromo diphenyl ether. The threshold for induction of the ethoxyresorufin O-deethylation or benzo[a]pyrene oxidation was between 3 and 10 mg/kg. In conclusion, with regard to the induction of cytochrome P-450 types pentabrominated diphenyl ethers behave as mixed-type inducers.

Adipose Tissue↗
PubMed1990

Purification of a rat liver cytosolic sulfotransferase responsible for the conjugation of digitoxigenin.

Previous investigations on the digitoxin metabolism hardly considered the role of the sulfate ester conjugation. Therefore, this study examined whether digitoxin (dt-3) or one of its cleavage products might be sulfated in vitro. It was proven that digitoxigenin (dt-0) is by far the best substrate for the cytosolic sulfotransferases (ST). Digitoxigenin-monodigitoxoside (dt-1) and digitoxigenin-bisdigitoxoside (dt-2) are sulfated in trace amounts whereas dt-3 is not sulfated at all. The purification of the responsible enzyme was performed by liquid chromatography on Q-Sepharose and hydroxyapatite. During the purification procedure this enzymatic activity corresponded exactly to that towards dehydroepiandrosterone (DHEA). The 134-fold purified and gel electrophoretically homogeneous enzyme protein (Mr 33,000) showed a Vmax of 12.5 nmoles dt-0 sulfate/min mg protein and a KM of 37 mumol/L. The purified enzyme conjugated dt-1 and dt-2 in trace amounts only and was inhibited competitively by DHEA. It can be concluded that in the rat a 3 beta-hydroxy-steroid sulfotransferase is responsible for the sulfation of dt-0. The purified enzyme reacts with dt-1, dt-2 and digoxigenin (dg-0) in traces only, a sulfation of dt-3 is not detectable.

Animals↗