Chromosomal aberrations in a patient with severe psychopathology.

The case of a female patient showing aggressive, compulsive, destructive behaviour, ritualistic faecal smearing, and hyperactivity is presented. The behaviour is long standing, therapy-resistant, and its aetiology is unknown, although it is seemingly associated with chromosomal abnormalities secondary to abnormal plasma factors.

(+)-4-Dimethylamino-2,alpha-dimethylphenethylamine (FLA 336(+)), a selective inhibitor of the A form of monoamine oxidase in the rat brain.

(+)-4-Dimethylamino-2,alpha-dimethylphenethylamine (FLA 336(+)) and its N-demethylated secondary amino derivative FLA 788(+) were examined for their monoamine oxidase (MAO) inhibitory effects in the rat brain. They were found to be reversible and very selective inhibitors of the A form of monoamine oxidase in vitro and in vivo after oral administration. FLA 788(+) was 2-6 times more active than FLA 336(+) in vitro depending on the assay technique employed but the two compounds had similar potency after oral administration. Both compounds inhibited competitively the deamination of 5-hydroxytryptamine by hypothalamic mitochondria. Although the irreversible inhibitor clorgyline was 60 times more potent than FLA 336(+) in vitro, it was equipotent with FLA 336(+) and FLA 788(+) in the rat brain after oral administration. There was a high correlation between the log plasma concentration of FLA 788(+) and the MAO inhibition in hypothalamic slices. The plasma concentration of the metabolite FLA 788(+) exceeded that of FLA 336(+) after oral administration of the latter compound. Thus, the MAO inhibition produced by FLA 336(+) in vivo, appears in part to be due to the metabolite FLA 788(+).

Studies on serum lipoproteins of rats developing spontaneous hyperlipidemia.

The lipid composition of the serum lipoproteins of Sprague-Dawley rats with varying degrees of hyperlipidemia was investigated. The concentrations of all the lipoproteins were increased with increasing hyperlipidemia. The elevation was found to be more pronounced for very low density VLDL) and low density (LDL) than for high density lipoproteins (HDL). A linear relationship exists between triglyceride and cholesterol contents of VLDL fractions independent of the VLDL level. Eighty to ninety per cent of serum triglycerides are located in the VLDL fraction. Linear relationships were found between the levels of serum triglycerides or VLDL triglycerides and the levels of LDL and HDL cholesterol, respectively. Furthermore, linear relationships exist between total cholesterol content in serum and cholesterol concentration in VLDL, LDL and HDL, respectively. Thus, lipoprotein levels may be estimated by measuring serum cholesterol or triglyceride concentrations. Disk electrophoresis and ultracentrifugation revealed that the LDL fraction (d. 1.006 - 1.063) could be divided into two fractions, which both increase with age. The spontaneous hyperlipoproteinemia of the old rats make these animals suitable as a model for evaluation of drugs against human hyperlipoproteinemia.

Lipoprotein lipase activity in adipose tissue of spontaneously hyperlipidemic rats.

The lipoprotein lipase activity in adipose tissue of Sprague-Dawley rats 1, 4, 9 and 15 months of age, was investigated. The study revealed that a significant inverse relationship exists between serum triglyceride level and lipoprotein lipase activity in epididymal fat pad. Thus, the lipoprotein lipase activity in 1 and 15 months old rats are on the average 5.3 and 1.1 nkat/g wet weight, respectively, simultaneously as serum triglyceride level increase from 0.74 mmol/l to 3.51 mmol/l, respectively. It is suggested that impaired removal of very low density lipoproteins is one possible explanation of the enhanced levels of this lipoproteins in the old rat. The lipase activity investigated had the characteristic properties of lipoprotein lipase, i.e. it was activated by the addition of serum, inhibited by high ionic strength and varied with the nutritional state. However, it could not be exclude that monoacylglycerol lipase present in epididymal fat pad also decreased with age. The possible connection between the age-related reduction of lipoprotein lipase activity in epididymal fat pad and the age-related gomerulonephritis found in these rats is discussed.

Dosage of i.v. brinase in man based on brinase inhibitor capacity and coagulation studies.

In 17 patients a total of 148 brinase infusions were given. All patients but two had anticoagulant treatment (dicoumarol or heparin) during the brinase series. Dosage of brinase was based on determination of brinase inhibitor capacity in plasma (azocollagen technique) prior to infusion of the enzyme. Iv infusion of brinase lowered inhibitors in plasma. Good correlation was found between expected lowering and measured inhibitor values after brinase infusion. The stipulated safety margin for brinase inhibitor capacity could be maintained. alpha 1-antitrypsin showed irregular changes and alpha 2-macroglobulin values were decreased by iv infusions of brinase. Fibrinogen values were somewhat lowered after iv brinase infusion. Values for fibrinogen degradation products increased and the ethanol gelation test became positive. Thrombotest values were lowered and the activated partial thromboplastin time was prolonged in patients receiving dicoumarol and iv heparin respectively. Changes in other coagulation parameters were insignificant. In two patients transient renal failure was recorded, laboratory data indicated intravascular coagulation as a possible cause. None of these two patients were on anticoagulant treatment. One patient developed a haematoma of the forefoot during massive iv heparin treatment during a series of iv infusions of brinase. Bleeding complications due to brinase treatment were not observed.