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Biomedical subjects

A H Stead

Publications and source records attributed to A H Stead.

At least 19 recordsLinked to original sources
PubMed1983

Quantification of the interaction between barbiturates and alcohol and interpretation of fatal blood concentrations.

Barbiturates and alcohol are frequently found in combination in cases of accidental or intentional fatal self-poisoning. Unfortunately, the lack of any precise knowledge concerning their interaction creates difficult problems when an interpretation of toxicological data is sought. 1 In the following work the joint action of single barbiturates and alcohol is examined and a means of quantifying it is presented. 2 The effects of different amounts of alcohol on fatal amylobarbitone, butobarbitone, pentobarbitone, phenobarbitone and quinalbarbitone blood concentrations are compared. 3 Combined alcohol-barbiturate blood concentration curves connecting those concentration pairs equally effective in causing death are used to quantify the increase in toxicity. The quantitative effects of alcohol appear to be greater with the shorter- and longer-acting barbiturates than with the intermediate-acting derivatives. The different modes of interaction are discussed in terms of the physico-chemical and pharmacokinetic properties of the drugs.

Barbiturates↗
PubMed1983

Therapeutic, toxic and fatal blood concentration ranges of antiepileptic drugs as an aid to the interpretation of analytical data.

1 Problems associated with the interpretation of analytical results are often related to the ineffective presentation of reference information. Concentration-response curves overcome many of the problems by presenting all available information concisely and by allowing clear comparisons between drug concentrations associated with different pharmacological responses. Although visual comparison of such curves is possible, it can be advantageous to represent them numerically. 2 Numerical representations are used in the present work to compare sub-therapeutic, optimally therapeutic, toxic (side-effects and severe effects), and fatal blood concentrations of the commonly prescribed antiepileptic drugs. 3 Blood drug concentrations accounting for 50% of the population (EC50) are expressed in relation to the concentrations accounting for 10% (EC10) and 90% (EC90) of the population in each clinical category. 4 Such EC10-EC50-EC90 ranges are shown to represent adequately the concentration-response curves. They demonstrate the overlap between drug blood concentrations associated with the various responses and give a good indication of the expected response at any concentration. The concentration ranges are therefore a very useful interpretative aid in therapeutic drug monitoring, emergency toxicology, and forensic toxicology.

Anticonvulsants↗
PubMed1983

A collection of therapeutic, toxic and fatal blood drug concentrations in man.

In order to assess the significance of drug concentrations measured in clinical and toxicological investigations, it is essential that good collections of data are readily available. As a guide to interpreting findings, the present work provides a compilation of therapeutic, toxic and fatal blood concentration ranges of 298 drugs of interest to clinical pharmacologists, clinical toxicologists, and forensic toxicologists. Wherever possible, ranges are expressed concisely in terms of the maximum blood concentrations which account for 10, 50 and 90% of the data collected. They provide easy access to the most reliable information which relates the blood drug concentration to the biological response it produces. Where appropriate, the different toxic effects of a drug and/or the different degrees of severity of toxic symptoms associated with different drug levels are clearly defined. The original sources of all data used are provided to allow the analyst to obtain further analytical, pharmacokinetic and toxicological information should this be necessary. Those factors (e.g. age, capacity for drug metabolism, drug interactions, etc) which can modify the relationship between a drug concentration and the response it produces are briefly discussed.

Data Collection↗
PubMed1981

Analytical aspects of barbiturate abuse: identification of drugs by the effective combination of gas-liquid, high-performance liquid and thin-layer chromatographic techniques.

Chromatographic retention data for a group of barbiturates have been measured on seven chromatographic systems (two gas--liquid chromatographic (GLC), three high-performance liquid chromatographic (HPLC) and two thin-layer chromatographic systems) and the value of these for barbiturate identification has been discussed. The overall correlations observed between pairs of systems are generally low; however, specific groups of barbiturates show very high correlations and this determines the approach to the selection of two or more systems to increase chromatographic discrimination of the barbiturate group. Column chromatographic techniques with lipophilic phases (GLC using SE-30, HPLC using ODS-silica) are most suitable for barbiturate identification. Changes of eluent pH in reversed-phase HPLC proved very effective for the separation of barbiturates with closely related structures.

Barbiturates↗
PubMed1980

Metabolism of extracellular glutathione in rat small-intestinal mucosa.

Metabolism of exogenous glutathione was investigated in suspensions of freshly isolated rat small-intestinal mucosal cells. The cells catalyzed the oxidation of reduced glutathione (GSH) to glutathione disulfide (GSSG). Neither serine . borate nor methionine significantly influenced this reaction. Formed GSSG was further metabolized as indicated by its disappearance from the medium. Degradation of GSSG was stimulated by methionine and inhibited by serine . borate. Separation and identification of GSSG metabolites were achieved by high performance liquid chromatography. The results indicate that the preferred route for GSSG metabolism to the constituent amino acids in small intestine, is by hydrolytic removal of the two gamma-glutamyl groups of GSSG to yield cystinyl-bisglycine which is subsequently hydrolyzed to cystine. gamma-Glutamyltransferase activity was compared in isolated intestinal, kidney and liver cells using gamma-glutamyl-p-nitrocarboxyanilide as substrate. Kidney cells were approximately 5-fold and 150-fold more active than intestinal and liver cells, respectively. Serine . borate markedly inhibited, and glycyl-glycine stimulated, hydrolysis of gamma-glutamyl-p-nitrocarboxyanilide in all cell types confirming the involvement of gamma-glutamyltransferase in the reaction. The hydrolysis of gamma-glutamyl-p-nitrocarboxyanilide was inhibited to approximately the same extent by either GSH or GSSG suggesting that both compounds interact at the donor site of gamma-glutamyltransferase. Comparison of the rates of glutathione metabolism by isolated intestinal and kidney cells suggests that the intestinal contribution to the degradation of extracellular glutathione may be physiologically more important than has previously been assumed.

Animals↗
PubMed1979

Glutathione depletion in isolated hepatocytes: its relation to lipid peroxidation and cell damage.

The effects of glutathione depletion in isolated hepatocytes have been studied. A list of compounds which depleted glutathione and induced lipid peroxidation and cell lysis is given. The effects of halogenated acetamides were studied in more detail and results of studies on the interaction of iodoacetamide with cellular constituents are presented. A single metabolite of iodoacetamide, tentatively identified as the glutathione conjugate, was excreted from the cells while less than one percent of the "parent compound" was retained, tightly bound to macromolecules. This bound component could not be associated with the cellular damage. Methionine, cysteine and alpha-tocopherol, as wellas paracetamol and ethylmorphine, were found to prevent lipid peroxidation and lysis. It is concluded that GSH deficiency per se can lead to lipid peroxidation and that this reaction caused the observed hepatocellular lysis.

Acetamides↗
PubMedDate not supplied

The development and evaluation of a 125I radioimmunoassay for the measurement of LSD in body fluids.

A radioimmunoassay (RIA) has been developed for the direct detection of LSD in biological fluids. The radiotracer, (+)-2-[125I]iodo-LSD, allows the use of gamma-counting rather than the liquid scintillation counting currently used for existing 3H radioimmunoassays. The assay is specific for LSD and very closely related compounds. It is inexpensive, sensitive, simple to use and small volumes of samples (50 microliter) can be assayed directly without the need for any time-consuming extraction procedures. The cut-off levels are 1.2 ng/ml in blood and 3.0 ng/ml in urine. The results obtained using the 125I assay described in this work compare very favourably with those obtained using the 3H assay currently used by Home Office Forensic Science Laboratories. The advantages of the assay make it a most appropriate method for the routine screening of LSD in biological samples of forensic interest.

Cross Reactions↗