Lipid peroxidation by bovine heart submitochondrial particles stimulated by 1,1′-dimethyl-4,4′-bipyridylium dichloride (paraquat)

Paraquat enhanced the NADH-dependent lipid peroxidation of bovine heart submitochondrial particles in the presence of ADE-Fe³⁺ chelate. The enhancement at physiological pH was about 3-fold. The pH optimum of the lipid peroxidation was shifted from pH 6.5 by paraquat. The submitochondrial particles catalyzed the reduction of paraquat when incubated anaerobically with NADH, whereas they did not reduce paraquat with succinate. The reduction was inhibited by phydroxymercuribenzoate or amytal, but it was not inhibited by rotenone, antimycin A or cyanide. The respiratory-chain inhibitors similarly affected the NADH-dependent O₂ consumption stimulated by paraquat, indicating that the NADH-dehydrogenase is involved in the reduction of paraquat at a region between the mercurial-sensitive site and the rotenone-sensitive site. The NADH-dependent reduction of ADP-Fe³⁺ chelate, a key step in lipid peroxidation, was stimulated by paraquat about 5-fold at physiological pH. The stimulation could mainly be ascribed to the direct electron transfer from a paraquat radical to the chelate and partially to the electron transfer from O₂^? produced by the reoxidation of the paraquat radical. ADP-Fe²⁺ produced lipid hydroperoxide in liposomes and decomposed cumene hydroperoxide. These reactions, the initiation reaction and the propagation reaction of peroxidation, were stimulated by paraquat. These results suggest that paraquat enhanced lipid peroxidation by stimulating (1) the reduction of ADP-Fe³⁺ chelate, and (2) the ADP-Fe²⁺-dependent initiation and propagation reactions of the peroxidation.     

Blood cyanide levels in mice after administration of amygdalin

Oral doses of amygdalin and intraperitoneal (i.p.) doses of potassium cyanide (KCN) in the near-lethal range were administered to CD2F1 female mice. Blood cyanide levels were then measured as a function of time. The maximum cyanide level after amygdalin administration was reached at about 1½ to 2 h and was within the range of values seen after KCN administration. Behaviour of mice correlated with the time of maximum blood cyanide level. Acute distress was observed at times when the cyanide level was highest. There was great variability in the nature and magnitude of the response in individual mice. The ability of the contents of various regions of the gastrointestinal tract and of tumour tissue to release cyanide from amygdalin was assessed. Stomach and upper intestine had little activity while the lower end and the faeces released large amounts. Again, there was a large variation between mice. These results are interpreted to mean that enteric contents are primarily responsible for the release of cyanide from ingested amygdalin. Freshly minced tumour tissue released negligible amounts of cyanide. Ten-fold higher doses of amygdalin administered i.p. produced very small increases in blood cyanide levels and no toxic behaviour. The doses used are comparable to doses which might be ingested by patients receiving oral amygdalin or Laetrile and indicate that oral amygdalin is potentially extremely dangerous.     

Activated charcoal impairs propantheline absorption

Summary 5 g activated charcoal BPC reduced the effects of 45–60 mg of propantheline given orally at the same time. This interaction may be important in patients taking remedies containing charcoal. Patients suffering from overdosage with quaternary ammonium compounds administered orally might benefit from immediate treatment with activated charcoal.     

Analysis of methaqualone in autopsy material

Summary A method for detection and determination of methaqualone and some of its metabolites in autopsy material is described, involving extraction, ultra-violet spectrophotometry, gas and thin-layer chromatography.Twenty autopsy cases of intoxications were investigated in a detailed fashion. In most cases, the concentration of metabolites in blood, liver and kidney were considerably lower than those of the parent drug, especially when other drugs and/or ethanol also were found. Only small amounts of methaqualone and free metabolites were present in the urine. However, after acid hydrolysis, considerable quantities of metabolites were liberated.A statistical survey of autopsy cases where methaqualone was detected in routine analyses are given. Between, 1964 and June, 197O, methaqualone was detected in 165 autopsy cases, about 90% of these being suicides. 22 cases were intoxications with methaqualone alone. In the remaining ones, death was due to combinations of drugs (including ethanol), or due to physical factors.From the material presented here, the lower limit of lethal concentration in blood seems to be 1–2 mg of drug per 100 ml in pure methaqualone intoxications.

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Zusammenfassung Eine Methode zur Isolierung und Identifizierung von Methaqualon (2-Methyl-3-o-4(3H)-chinazolinon) in Leichenmaterial wird beschrieben. Proben von Leber bzw. Niere werden mit Äthanol homogenisiert und die Suspension zentrifugiert. Die klare Lösung wird abdekantiert und eingedunstet. Im übrigen, sowie auch für Blut und Harn, wurde das Verfahren von Bonnichsen u. Mitarb. (1961) und Maehly und Bonnichsen (1966) verwendet.Um unverändertes Methaqualon in den Extrakten zu bestimmen, wurden diese gaschromatographisch untersucht. Als stationäre Phase wurde 1% HiEff 3 A verwendet (ein Polyester von Applied Science Laboratories, U.S.A.) und als Träger Gas Chrom Q bei einer Kolonnentemperatur von 190°. Unter diesen Verhältnissen wurden Metaboliten des Methaqualons nicht eluiert.Mit Hilfe der Ultraviolett-Spektrophotometrie wurde die Gesamtmenge von Methaqualon und gewissen Metaboliten mit annähernd gleichen Spektren bestimmt. In einigen Fällen wurden Extrakte von Blut, Leber und Niere auch dünnschicht-chromatographisch untersucht. Auf den Chromatogrammen konnten außer Methaqualon 3 andere Flecken (manchmal nur 1 oder 2), die mit Dragendorffs Reagens angefärbt werden und Metaboliten von Methaqualon darstellen, entdeckt werden (Abb. 2). Die Metaboliten wurden nicht identifiziert.Mit den genannten Methoden wurden 20 Fälle von tödlichen Vergiftungen (im allgemeinen Suicide) untersucht. Die Resultate sind in Tabellen 1 und 2 angegeben. Der Anteil von Metaboliten war im allgemeinen viel niedriger als der des unveränderten Methaqualons, besonders wenn auch andere Arzneimittel oder Äthanol vorlagen. Bemerkenswert niedrige Konzentrationen von Metaboliten zeigte Fall Nr. 7 (Tabelle 2), in welchem auch hohe Konzentrationen von Salicylsäure gefunden wurden.Im Harn wurden nur geringe Mengen von Methaqualon oder freien Metaboliten nachgewiesen, saure Hydrolyse setzte hingegen große Mengen gebundene Metaboliten frei. Im Blut oder in den Organen wurden nur unbedeutende Mengen von gebundenen Metaboliten entdeckt.

     

Effect of tetraethyl lead on food and water intake in the rat

The effect of tetraethyl lead (TEL) on food and water intake in adult male albino rats was studied. Animals received 1, 4, 7, 10, or 13 mg/kg body weight of TEL in peanut oil, or a peanut oil placebo, via either intragastric (IG) intubation or intraperitoneal (IP) injection. For food intake, route of administration was a significant factor and, compared to baseline levels, food intake was significantly depressed at dosage levels of 7, 10, and 13 mg/kg for both IP and IG administration. Further, the time course of food intake differed significantly across route of administration. Water intake was also significantly depressed at 7, 10, and 13 mg/kg, but route of administration was not a critical factor. Results were discussed in relation to clinical and experimental data on lead intoxication, and were viewed as severely limiting the utility of employing food and/or water as motivational variables in assessment of behavioral effects linked to TEL poisoning.     

Carbon tetrachloride poisoning in Reykjavík and vicinity

Summary A report is given of all known cases of carbon tetrachloride poisoning treated at hospitals and/or coming to autopsy at the Department of Pathology, University of Iceland, Reykjavík, during the 20-years period 1945–1964.The main features of each case are summarized in the table. On the basis of previous report (Bjarnason et al.), it was concluded that carbon tetrachloride must be a considerably more toxic substance than trichloroethylene.Department of Pathology, University of Iceland, Reykjavík; Head: ProfessorNiels Dungal (deceased Oct. 29th, 1965).Department of Pharmacology, University of Iceland, Reykjavík; Head: ProfessorKristinn Stefánsson.The Sct. Joseph's Hospital, Reykjavík; Head:Bjarni Jónsson, M.D.     

X-Ray microanalytical studies of lead-implanted rat brains

Summary Various cytoplasmic and intranuclear inclusions found in macrophages and astrocytes of lead-implanted rat brains were studied with an energy dispersive x-ray microanalytical technique. Cytoplasmic inclusions contained large quantities of lead, calcium and phosphorus. The proportions of these elements were different within each inclusion. Intranuclear inclusions also contained small amounts of lead and, occasionally, calcium.     

Physical Properties of Fluorosis Bone: Critical Comments

In 1976 Franke and co-workers reported a study of the physical properties of bone from patients who had been exposed to fluorine for many years.¹ In addition the ash from a rib and an iliac crest was examined and found to contain considerable amounts of fluorine. In the mechanical tests, determinations were made of the fracture load and bending strength of complete bones or parts of bones, and of the fracture load per unit of area and the modulus of elasticity of cylindrical test bodies made from bone specimens.