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Biomedical subjects

B Holmstedt

Publications and source records attributed to B Holmstedt.

At least 19 recordsLinked to original sources

[The sleeping girl from Oknö].

The peninsula of Oknö is located on the Baltic in Southern Sweden. It was here a 14 year-old girl "fell asleep" around Christmas time in the year 1875 - she woke up on April 3rd, 1908. She was then 46 years of age and had slept for 32 years. Except for numerous newspaper articles this unusual case has been described by the Swedish psychiatrist Harald Fröderström in 1912. The present article is based on his review and the investigation of the medical records at the hospital of the city of Oskarshamn where the woman in question was hospitalized for one month in 1892. At the city hospital she was given the diagnosis dementia paralytica - a diagnosis which was obviously wrong. When the woman woke up in 1908 she assumed a normal life and remained healthy until she died in 1950 through a brain hemorrhage. Fröderström, who except for an article written in French, wrote several extensive articles for Swedish newspapers about the sleeping girl. These articles are here reviewed from a modern psychiatric point of view.

Adolescent↗

Was opium known in 18th dynasty ancient Egypt? An examination of materials from the tomb of the chief royal architect Kha.

Examination by microscopy, thin-layer chromatography, gas-liquid chromatography alone and combined with mass spectrometry, and radioimmunoassay methods of materials from the tomb of the ancient Egyptian chief royal architect Kha, who is believed to have died about 1405 BC, has shown that there is no morphine--and hence no opium--present. This finding casts doubt on the results of an earlier analysis. Tropane alkaloids are likewise absent. The significance of the present findings for the history of the opium poppy, Papaver somniferum L., in the eastern Mediterranean region is discussed. Evidence (chemical, botanical, artefactual, and linguistic) for the supposed presence of the opium poppy and opium in Egypt in the Late Bronze Age is briefly reviewed. These considerations and the negative outcome of the present analyses mean that the earlier reported finding can no longer be accepted as evidence.

Egypt, Ancient↗

Intoxications with anticholinesterases: effect of different combinations of antidotes on the dynamics of acetylcholine in mouse brain.

Intoxications with organophosphorus compounds are normally treated with a mixture of atropine and an enzyme regenerating oxime. The addition of diazepam to the conventional drug therapy is reported to greatly improve the antidotal effect. The implication of the cholinergic system in such intoxications prompted us to study the effect of different combinations of antidotes on the acetylcholine (ACh) synthesizing system in mouse brain in vivo. The antidotes studied in this paper are diazepam, HI-6 and 1-hyoscyamine, the active enantiomer of atropine. Diazepam decreases the synthesis rate of ACh both when administered separately and in combination with 1-hyoscyamine and HI-6. This is in contrast to 1-hyoscyamine which, in addition to blocking muscarinic receptors, also increases the release and rate of synthesis of ACh, which probably is an unfavourable effect of the antidote. This might at least partly explain the advantage of combining 1-hyoscyamine and an oxime with diazepam in intoxications with anticholinesterases. Mice administered soman (0.75 x LD50), after pretreatment with the three-drug combination of antidotes, show no cholinergic symptoms despite a 50% increase in endogenous ACh. The rate of synthesis of ACh in these mice is in the same range as in animals administered diazepam alone. Mice administered the same dose of soman with no antidotal pretreatment suffer from severe tremor and salivation, and have a strongly reduced synthesis rate of ACh.

Acetylcholine↗

Distribution and elimination of the stereoisomers of soman and their effect on brain acetylcholine.

The four stereoisomers of soman (O-(1,2,2-trimethylpropyl)-methyl-fluorophosphonate) have been analyzed in vivo in mouse blood and tissues after administration of doses corresponding to 0.75 X LD50 of the two diastereoisomeric pairs of soman (Sc- and Rc-soman). The disappearance of the four isomers has been studied in vitro in the presence of enzymes involved in the toxicity and detoxification of soman, e.g., acetyl- and pseudocholinesterase, aliesterase, and phosphorylphosphatase. The effect of Sc- and Rc-soman on brain acetylcholine was studied in the mouse. The analytical methods used are based on gas chromatography-mass spectrometry with deuterated internal standards. Rc-Rp- and ScRp-soman, the two isomers that preferentially react with acetylcholinesterase, were found in blood and liver. In liver the concentration of ScRp was higher than that of RcRp and could be followed for 18 hr. In blood only ScRp could be found. Its presence there could be followed during 18 hr. The levels were, however, lower than in liver. The results indicate that the liver might be a depot for soman and that ScRp might be responsible for the delayed intoxication noted after treatment with antidotes. Rc-soman was found to have a more pronounced effect on the acetylcholine synthesizing system than has Sc-soman, which might explain its higher in vivo toxicity.

Acetylcholine↗

Stereoselectivity of enzymes involved in toxicity and detoxification of soman.

The fate of the four stereoisomers of soman [0-(1,2,2- trimethylpropyl )-methyl-fluoro phosphonate] has been studied a) in vivo in mouse blood and liver after IP injection of 0.75 X LD50 RC- and SC-soman respectively, and b) in vitro upon incubation with acetyl- und pseudocholinesterase, aliesterase and phosphorylphosphatase . The analytical method used is based on gas chromatography-mass spectrometry with deuterated internal standard. Most soman disappeared very rapidly from blood and liver. In liver, SCRP and RCRP , the two isomers that preferentially react with cholinesterase, could be detected. The level of SCRP , which was higher than that of RCRP , could be followed for 17-18 h. In blood only SCRP could be detected. The amounts found were fairly constant during the time period 2 min to 4h, and it could even be detected 17-18 h after soman administration.

Acetylcholinesterase↗

Presence of formaldehyde in biological media and organic solvents: artifactual formation of tetrahydro-beta-carbolines.

A gas chromatography-mass spectrometry method is described for the identification and quantitation of 6-hydroxy-1,2,3,4-tetrahydro-beta-carboline (6OHTHBC). During the analysis of 6OHTHBC in human platelets, the artifactual formation of 6OHTHBC was observed and shown to be due to the presence of formaldehyde in both organic solvents and in platelet homogenates. Formaldehyde was facilely removed from the organic solvent via a Pictet-Spengler reaction; however, removal from tissue homogenates was not possible by using conventional aldehyde-trapping agents. The solution of these problems and their consequences for persons attempting to establish the in vivo presence of tetrahydro-beta-carbolines or biochemically study tissue preparations are discussed.

Blood Platelets↗

Guide to the analysis of phencyclidine and its metabolites in biological material.

Phencyclidine was introduced as an anaesthetic in 1960; and has now become a major drug of abuse in some countries. The rapid advance in the various fields of analytical chemistry during the past decades has made it possible to measure the levels of the compounds in tissues and body fluids. These methods may also be used to study the metabolism and pharmacokinetics of PCP. The resulting publication is an updated guide to these analyses particularly with the application of these techniques in human intoxication.

Biotransformation↗

Smoking and sister chromatid exchange.

Smokers were shown to have significantly higher SCE levels in peripheral lymphocytes than non-smokers. The increase of SCE was found to depend on the cigarette consumption, and to be significantly higher in subjects with a long than with a short history of smoking. Analysis of the frequency distribution of individual SCE levels and of SCE numbers in single cells gave no indication of subgroups of individuals of subpopulations of lymphocytes with an increased SCE response to smoking. Cells from smokers cultivated in plasma from non-smokers retained a high SCE level, and cells from non-smokers cultivated in plasma from smokers no increase of SCE, indicating that the increase of SCE caused by smoking is due to some type of (long-lived) cellular damage rather than to serum factors. The plasma levels of the primary nicotine metabolite cotinine were found to be increased in heavy smokers as compared to light smokers, and showed an excellent correlation with the cotinine levels in the amniotic fluid in pregnant female smokers. No correlation was found between the individual SCE and cotinine levels in smokers, which indicates that the degree of exposure to SCE-inducing genotoxic agents in the cigarette smoke is not related to plasma cotinine levels in any simple way. The induction of DNA strand breaks and SCE by two intermediary benzo(a)pyrene (BP) metabolites was studied in human lymphocytes in vitro. Both 9-OH-BP and BP-7,8-dihydrodiol were found to induce DNA breaks, but only the latter compound induced SCE. The SCE-inducing effect of BP-7,8-dihydrodiol was observed at a very low concentration (0.01 microM), which indicates a possible role for this BP derivative in the smoking-induced increase of SCE in vivo.

Benzopyrenes↗