Stepwise precipitation method of human blood lipoproteins for clinical routine.

A three-step precipitation method for separate measurement of the lipid and protein composition of the main serum lipoprotein classes has been developed. The consecutive procedure applying phosphotungstic acid, polyethylene glycol and dextran sulfate makes the analysis of chylomicron, VLDL, LDL, HDL2 and HDL3 possible. Because of simplicity and appropriate accuracy the method may be suitable for systematical use in clinical laboratories. A relatively large scale investigation on hyperlipidemic patients by clinics disposing of regular service could be managed with the aid of the method. In this study the lipoprotein composition of a limited number of normal, type IIA and type IV hyperlipidemic patients has been investigated. The results were compared to the international standard values.

Accumulation of cholesterol ester in cultured smooth muscle cells of congenital hypercholesterolemic (WHHL) rabbits treated with normal and WHHL rabbit plasma LDL.

The DNA content, thymidine incorporation into DNA, and free and esterified cholesterol contents of cultured aortic smooth muscle cells (SMCs) of normal and WHHL rabbits were compared. In the first series of experiments, 5 groups of cultured normal rabbit aortic SMCs were compared: control cells and cells treated with LDL from normolipemic rabbit plasma (LDLN) and (DL from hypercholesterolemic rabbit plasma (LDLW), LDLN plus esterastin and LDLW plus esterastin. In the second series, the same groups of hereditable hypercholesterolemic WHHL rabbit aortic SMCs were compared. Results obtained with normal aortic SMCs showed that internalization of LDLW was higher than that of LDLN. LDLW was also more effective than LDLN for elevating thymidine incorporation into DNA. LDLW plus esterastin caused increases of 5, 7 and 3 times the control values in thymidine incorporation, and esterified and free cholesterol contents of the cells, respectively. In the control groups, thymidine incorporation into DNA of WHHL SMCs was 12 times more than that into the normal cells, and the free cholesterol content of WHHL cells was twice that of normal cells. Addition of LDLN caused further increases in thymidine incorporation and the esterified and free cholesterol contents of the cells. Esterastin had only a slight effect on these extremely high values. LDLW itself had no effect except that when added with esterastin it increased the cholesterol ester content of WHHL cells. The results are discussed with respect to metabolic differences between cultured aortic SMCs of normal and WHHL rabbits, and LDLs prepared from normal and hypercholesterolemic (WHHL) rabbit plasma.

Investigation of the interaction between Probon and indomethacin in rats.

The toxic side-effects and anti-inflammatory activity of combination treatment of Sprague-Dawley rats with indomethacin and Probon, a new type of analgesic, were investigated. Following four weeks of treatment with a combination of these two drugs, the characteristic gastrointestinal side-effect of indomethacin was markedly reduced. Mortality resulting from administration of the drug combination was significantly lower than that resulting from indomethacin treatment alone. The reduced toxicity of indomethacin in combination with Probon is probably due to a change in metabolism produced by the hepatic microsomal enzyme inducer, Probon. The anti-inflammatory effect was also investigated using a contact thermographic method following one, three or seven days pretreatment. The advantage of this combination is that, using a higher dose of indomethacin in combination with the minor analgesic, we could achieve a more reliable anti-inflammatory effect together with a pain-killing action.

Effect of CH-1243, a pyrido (1,2-a) pyrimidine derivative on the elevated activity of lysosomal enzymes of rabbit aorta and liver in experimental atherosclerosis.

The effect of CH-123 (3-carbethoxy-6-methyl-1-9-(carboxy-methyl)-1-4-oxo-6,7,8,9-tetrahydro-4H-pyrid o(1,2a)pyrimidine) was investigated on the activity of 4 lysosomal enzymes: beta-glucuronidase, beta-galactosidase, N-acetyl-beta-glucosaminidase and acid phosphatase obtained from aortic smooth muscle and liver cells of rabbits. Animals were fed on a 2% cholesterol diet for 4 weeks and used an experimental atherosclerotic group. In drug-treated groups, after 4 weeks of cholesterol feeding the diet was changed to regular food and the animals were treated daily either with 50 mg/kg CH-123 or with 250 mg/kg Clofibrate. The postnuclear supernatant of homogenates of liver and aortic cells was isolated, lysosomes were fractionated by sucrose density gradient centrifugation, and the activity of enzymes was measured. In cholesterol-fed animals the enzyme activities of aorta and liver was 3-5 times higher than in the control, i.e. in the group of rabbits fed regular food. On Clofibrate treatment the enzyme activities were 2-3 times higher, but on treatment with CH-123, they were only 1.2-1.8 times above the control. Experiments suggest that CH-123 treatment suppresses the elevated lysosomal marker enzyme activities in aortic and liver cells of atherosclerotic animals.

Experimental models of atherosclerosis (the insudative theory).

Atherosclerosis, a disease of multifactorial origin, can be promoted or caused experimentally by a wide variety of methods. The leading role of altered endothelial permeability, as well as different experimental techniques for producing changes in permeability, have been discussed by selecting the insudative theory as a working hypothesis. An attempt has been made to prove that by altering the endothelial permeability with different types of injuries, atherosclerotic vascular damage can be provoked with or without hypercholesterolemia.

Nitrogen bridgehead compounds. Part 7: Synthesis of anti-atherosclerotic pyrido[1,2-a]pyrimidines.

The synthesis of 9-substituted-pyrido[1,2-a]pyrimidines are described. The new compounds exhibit antiatherosclerotic effects. The 3-ethoxycarbonyl-6-methyl-4-oxo-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidine-9-acetic acid (Chinoin-123) has the most favourable effects.

Effect of CH-123 on vascular cholesterol deposition in experimental atherosclerosis of rabbits.

The effect of CH-123, a new antiarteriosclerotic pyrido-1,2a-pyramide derivate was checked in experimental atherosclerosis of rabbits. Cholesterol deposition was found to continue after 4-week cholesterol feeding even after the cholesterol level had returned to normal. This allowed to study the action of drugs in a phase dominated by lipid apposition to the vascular wall. In the experiments, clofibrate was used for reference. As judged by the lipid values in serum and aortic wall, CH-123 reduced substantially the deposition of lipids, mainly of cholesterol, into the aortic wall.

[A new diet for inducing early experimental atherosclerosis in rabbits]. / Korai kísérletes atherosclerosis eloidézése nyulakban új diéta-kombinációval

Authors by a new combined diet consisting of cholesterol vitamin D3 and sour cream produced clinico-biochemical changes characteristic for atherosclerosis in a very short period in rabbits. This diet caused severe lipoproteinaemia, hypercholesterinaemia and microscopis and macroscopic changes in the aortic wall. Authors assume, that this diet is suitable for producin atherosclerosis in a short period.

[Clinical use of prostaglandin antagonists in obstetrics]. / Klinische Anwendung der Prostaglandin-Antagonisten in der Geburtshilfe

The Department of Obstetrics and Gynecology in the Institute of Postgraduate Medical School (Budapest) reports on the treatment of 136 gravidities with the medicamentation of Prostaglandin-Antagonist.

[A new method for the study of flow of material into surviving blood vessel segments]. / Uj módszer túlélö érszeletek anyagbeáramlásának vizsgálatára

One of the most important questions arising in experiment on surviving segments of vessels is the question of flow of material into the vessel wall through the intima or adventitia. To make a distinction is important for the interpretation of results of in vitro experiments. By using a "tissuephil" tested already in practical surgery wound-adhesive free of any noxious effect, authors could form segments of vessels, having an only intimal or adventitial surface. Using this technique the flow of blood into the wall through intima or adventitia could be investigated separtely. At in vitro experiments most part of the labelled material flows into the vessel wall through the adventitia. This fact can be explained by the presence of microinjuries of the adventitia caused by the removing of the surrounding fat tissue. It is believed that only the flow through the intima gives an information about the condition of the vessels. Flow through the adventitia is mostly artificial.