Biomedical subjects
Publications and source records attributed to G Samsioe.
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Twenty women in the perimenopause were studied for 12 months during which sodium-piperazine-estrone-sulphate 2.5 mg/day was given for 3 weeks out of 4 as a hormone replacement therapy. Blood samples were drawn at the start of therapy, then after 3, 6 and 12 months and analyzed for serum triglyceride, total cholesterol, cholesterol content of high density lipoprotein (HDL) fraction and the relative fatty acid composition of serum lecithin. Triglyceride levels were increased after 3 months (p less than 0.01). After that there was a gradual decline to almost pretreatment levels. Total cholesterol decreased during the latter period of treatment and became virtually normal; significantly lower levels (p less than 0.01) were found at 12 months. The HDL-cholesterol, which constitutes most of the high density lipoprotein fraction, showed a continuous increase and reached statistical significance at 12 months (p less than 0.01). This type of lipoprotein pattern is associated with a reduced risk of ischemic cardiovascular disease. After 3 and 6 months of treatment an increase in the relative content of palmitic acid in serum lecithin was seen, an increase that might indicate an altered liver lecithin synthesis, usually seen in cholestasis. However, after 12 months the palmitic acid level declined and was not significantly altered from the pretreatment value, indicating that the change was transitory.
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Eight bilaterally oophorectomized women were given a depot injection of 200 mg DHEA-enanthate to study the effect on endocrine and lipid metabolism. A decrease in sex-hormone binding globulin (SHBG) and an increase in androstenedione was found 14 and 30 days after the injection. No changes could be detected in LH, FSH, oestrone, oestradiol or oestriol. Testosterone showed a tendency towards an increase. As compared to pre-treatment values, plasma lipids were unaltered after 30 days. A decrease in high density lipoproteins (HDL), cholesterol and in very low density lipoproteins (VLDL), free cholesterol, total cholesterol and phospholipids were seen in the lipid composition of the lipoproteins on day 30. These findings are in agreement with previous data reported after the administration of drugs with androgen-like effects. The relative fatty acid composition of plasma lecithin revealed only minor changes while the fatty acid composition of cholesterol esters indicated a decreased portion of essential fatty acids. These results suggest, in agreement with previous studies, an impaired endogenous cholesterol formation in the liver. The results from the analysis of the fatty acid composition of lecithin and cholesterol esters might indicate a decreased percentage of exogenous (dietary) cholesterol ester in plasma.
11 oophorectomized women (mean age 34.5 +/- 5.9) were given the 17-C-alkylated ethinyl estradiol (EE) 20 microgram/day and the non-alkylated estrogen, estradioil valerianate (E2V) 2 mg/day for 6 weeks in separate periods preceded by 6 weeks without hormonal replacement therapy. Blood samples were drawn before and after 6 weeks on each estrogen. Serum phospholipids, cholesterol and triglycerides were assessed. Preparative ultracentrifugation with the isolation of the very low density (VLDL; d < 1.006 g/ml); the low density (LDL; d = 1.006-1.063 g/ml) and the high density lipoprotein (HDL; d > 1.063 g/ml) fraction was carried out. In the three lipoprotein fractions, phospholipid, total cholesterol, free cholesterol and triglycerides were determined. An oral glucose tolerance test with concomitant plasma insulin determination was performed. In the present study EE caused an increase in serum total and LDL triglycerides while there was a reduction of triglycerides in serum as well as in VLDL and LDL when E2V ws administered. There was a positive correlation between plasma insulin values during oral glucose tolerance test and serum and VLDL triglycerides when E2V was administered. This finding supports earlier studies indicating that insulin (or rather the insulin-glucagon relationship) influences the hepatic triglyceride production rate. Both EE and E2V increased HDL cholesterol, but E2V did not induce a concomitant increase in serum triglycerides which would suggest a more physiological effect from the latter compound since fertile females have lower serum triglycerides and higher HDL cholesterol levels than males of corresponding age. The same differences are true in a comparison between fertile and post-menopausal women.
Ten oophorectomized women (ranging in age from 27 to 45 years, having a mean age of 34.5 years with a standard deviation of 5.3) were given three different progestogens (norgestrel, norethisterone and medroxyprogesterone) in treatment periods of 3 weeks' duration immediately preceded by 3 weeks "wash out" periods. Venous blood samples were drawn before and after each treatment period. Free and total cholesterol, triglycerides and phospholipids were determined in the three lipoprotein fractions: Very low density lipoproteins (VLDL), low density lipoprotein (LDL) and high density lipoprotein (HDL). Individual phosphatides were determined after thin layer chromatography. In addition, the relative fatty acid composition of serum lecithin and cholesterol esters were assessed by gas-liquid-chromatography. Both norethisterone and norgestrel caused a decrease in alpha-lipoprotein cholesterol. The relative fatty acid composition of serum lecithin revealed an increase of biochemical pathway 1 for liver lecithin synthesis on norgestrel and norethisterone but no major changes on medroxyprogesterone. With norgestrel an increase in serum-lysolecithin concomitant with a decrease in lecithin was observed, while the two other progestogens did not induce any significant changes. From the present data it is suggested that the 19-norethisterone derivatives, norethisterone and especially norgestrel, have androgen-like influences on lipid metabolism. Medroxyprogesterone, being a 17-alpha-hydroxyprogesterone, caused less changes and consequently less disturbance of lipid metabolism.
Eight pregnant women, complaining of generalized pruritus with lipoprotein-X (LP-X) in their serum and diagnosed as cases of cholestasis of pregnancy (CP)--were studied during pregnancy and after delivery. Ten women with uncomplicated normal pregnancy served as controls. LP-X, liver function tests and relative fatty acid composition of serum lecithin (determined by gas-liquid chromatography, GLC) were followed. The fatty acid composition in liver and serum lecithin is determined by the synthesis pathways of lecithin in the liver. The faster and quantitatively dominating cytidine-diphosphate diglyceride pathway, pathway I, causes the appearance of lecithin with palmitic acid (16:0) in 1-position and oleic (18:1) or linoleic (18:2) acid in 2-position, while pathway II, with methylation of phosphatidyl-ethanolamine (cephalin) preferentially cases the appearance of lecithin with stearic acid (18:0) in 1-position and arachidonic acid (20:4) in 2-position. Pathway I is enchanced by oestrogenic and pathway II by cholestatic influence. During pregnancy women with CP were characterized in their serum lecithin fatty acid composition by a high palmitic (16:0) and a high oleic (18:1) acid content, in agreement with earlier studies. After delivery, in women with prior CP a decrease in palmitic (16:0) and linoleic (18:2) acids and an increase in stearic (18:0) acid, was interpreted as decreased influence on the major lecithin synthesis pathway I and an enhancement of pathway II. In addition, after delivery in the lactating mother, serum lecithin fatty acid composition data revealed an essential fatty acid (EFA) "consumption." It was earlier shown, that women with previous CP (when studied 8--21 months after delivery) had as judged from their serum lecithin fatty acid composition, a "basic metabolic defect," expressing presumably as estrogen enhanced pathway II of liver lecithin synthesis. In the present study, soon after delivery (on day 4--8) women with prior CP showed, however, less pathway II influence than women with a prior normal pregnancy. This was interpreted as a presistence of the cholestatic influence on liver lecithin synthesis pathways at this short time after delivery. Serum lecithin fatty acid composition appears to be a sensitive variable for the evaluation of metabolic influences in the liver.
Serum lipids and fatty acid composition of serum lecithin were studied 8-21 months after delivery in 20 non-pregnant women who during their latest pregnancy had presented signs of CP. These women were compared with normal non-pregnant women (n=18) and with patients with cholestasis of pregnancy (CP) (n=28). In the non-pregnant state women with previous cholestasis of pregnancy (CP) showed in serum lecithin a low relative content of palmitic (16:0) and linoleic (18:2) acids and a high portion of stearic acid (18:0). These findings indicate as a basic defect in CP, a reduction in liver lecithin synthesis via pathway I (Kennedy's pathway) in favour of an increased pathway II (Greenberg's pathway). These data further support the hypothesis of increased estrogen activity as an etiological factor in CP. The basic influence by pregnancy on serum lipids and serum lecithin fatty acid composition was the same in women with CP as in women with a normal pregnancy.
The serum lipid values at different stages of pregnancy in twenty-six pregnany diabetic women attending a special antenatal clinic at the Department of Obstetrics and Gynecology, were compared with the corresponding values in four control series composed of non-diabetic pregnant women. Control series were studied at weeks 10, 22, 34 and after delivery, respectively. Serum triglycerides were higher in the diabetic women at week 10 (p less than 0.01), week 34 (p less than 0.05) and after delivery (p less than 0.05). Furthermore, in the diabetic women, infant birth weights were correlated (r=0.52, p=0.05) with maternal serum triglyceride values at week 31. Women with the highest serum triglyceride values (greater than 250 mg/100 ml) were delivered of infants with a higher birth weight (p less than 0.05) than those women with lower serum triglyceride values (less than 250 mg/100 ml). Intra-uterine deaths (n=4) were not related to maternal serum triglyceride values, but mean blood glucose values (during the whole pregnancy) were higher (p less than 0.001) in mothers with intra-uterine deaths. Elevated plasma free fatty acids (FFA) in the diabetic mother would be a possible cause for elevated serum triglycerides through increased liver triglyceride synthesis, while in the fetus an excess of plasma FFA (passing through the placental barrier) together with normal or elevated plasma insulin would be a likely explanation for increased triglyceride synthesis in adipose tissue and thereby of increased fat depots and body weight.
In cholestasis, serum lipids are altered. The alterations could at least partially be ascribed to the occurrence of an abnormal lipoprotein, LP-X. In 103 patients with jaundice, out of whom 16 had extra-hepatic cholestasis, the presence of LP-X was tested and semi-quantificated (by visual grading) utilizing an immunological technique. In extra-hepatic cholestasis, all patients showed LP-X in serum, while in intra-hepatic drug-induced cholestasis 87% revealed this phenomenon. At the initial stage of acute hepatitis, in drug-induced cholestasis, and in extra-hepatic cholestasis, the semi-quantificated LP-X correlated with alkaline phosphatase values. In extra-hepatic cholestasis, LP-X disappeared soon after the obstruction was relieved by operation.
Forty-one pregnant women with pruritus, in whom cholestasis was verified by the presence in their serum of an abnormal lipoprotein, lipoprotein-X (LP-X), were divided into two clinical groups, pruritus gravidarum (PG) (n=20) and hepatosis of pregnancy (HP) (n=21) in relation to serum bilirubin (below and above 1.2 mg/100 ml, respectively) and/or SGOT, SGPT (below and above 50 units/l, respectively). In HP, but not in PG, serum lipids, i.e. cholesterol, phospholipids, triglycerides, pre-beta-lipoproteins (very-low-density lipoproteins), and low-density lipoproteins were increased and high-density lipoproteins decreased when compared with suitable controls. Serum lipids were elevated in proportion to the derangement in the liver function tests, alkaline phosphatase, SGOT, and SGPT. The occurrence of LP-X was inversely related to HDL cholesterol, suggesting a causal relationship between HDL lipid metabolism and the presence of LP-X. Serum TIBC, Simplastin A, and serum iron were elevated in HP in relation to the degree of deterioration of liver function tests. Some of these changes in serum in cholestatic pregnancy may partially (serum triglycerides and pre-beta-lipoproteins) or completely (TIBC and Simplastin A) be explained by an enhanced estrogen influence in promoting increased liver lipid/protein metabolism.
Anion exchange resins form a non-absorbable complex with bile acids in the intestine, thus removing bile acids from the enterohepatic circulation and facilitating bile acid excretion in the faeces. A new bile acid sequestrant (PDX chloride, Secholex) was evaluated for the relief of pruritus in cholestasis of pregnancy (CP) in 31 women. CP was verified by the presence of the abnormal lipoprotein X in serum and the clinical series was divided into two degrees of severity, pruritus gravidarum (PG) and hepatosis of pregnancy (HP) based on liver function tests. Eleven of 31 women discontinued treatment because of gastro-intestinal side effects. Of the 20 women continuing the study for more than one week, all with a milder form of cholestasis, PG (n=8), experienced relief of pruritus, while some relief was obtained in 75% of the women with HP. After up to 4 weeks administration of Secholex, no obvious interference with fat absorption was evident judging from the serum lecithin content of linoleic and arachidonic acids. A reduction in serum folic acid might indicate an interaction in folic acid absorption. An expected reduction in serum cholesterol levels which are characteristically increased in CP, was not achieved by the administration of Secholex.
Women from an earlier series of cholestasis of pregnancy (CP) were called for a retrospective study to consider presence of gallstones in the gallbladder (evaluated by cholecystography), liver function tests, serum lipids and lipoproteins and the relative fatty acid composition of serum lecithin (as determined by GLC). The attendance in the retrospective study was 60%. Estimated on the total series (assuming that none of the non-responders would have a positive X-ray), the incidence of gallbladder disease was 23.7%. Among women with previous cholestasis of pregnancy and with a positive X-ray finding no characteristic changes in liver function tests or serum lipids were revealed. The women with positive X-ray had, however, a lower alpha-lipoprotein cholesterol than women with negative X-ray. A characteristic finding among women with positive X-ray was furthermore the low relative content of palmitic acid (16:0) in serum lecithin. Also women with negative X-ray had a lower relative content of palmitic acid than controls. It is suggested that the low palmitic acid content is expressive of an influence on liver lecithin synthesis pathways and that the serum lecithin fatty acid composition reflects similar changes in bile lecithin. The "basic defect" in CP influencing liver lecithin synthesis might be the primary cause for disturbed cholesterol solubility in bile and of the frequent occurrence of gallstones in CP.
The influence of cholestasis of pregnancy (CP) on liver lipid synthesis as reflected by the composition of serum phosphoglycerides was studied in 28 pregnant women in the last trimester by means of gas-liquid-chromatography (GLC). All patients complained of pruritus and had immunologically detectable lipoprotein-X (LP-X) in serum. Twenty women with uncomplicated pregnancies served as a control series. In lecithin, low palmitic acid (16:0) and high oleic acid (18:1 (n-9)) were found which appear to be characteristic for CP. The increased oleic acid suggests an enhanced liver lecithin synthesis through the cytidine-diphosphate diglyceride pathway. Measurement of the concentrations of lecithin from the gas-liquid-chromatograms was made possible by the use of an internal standard fatty acid added, which gave a linear relation to direct determination of lecithin. For further studies of influences of cholestasis of pregnancy on the relative fatty acid composition, lecithin was chosen because differences between lecithin (PC) and phosphoglycerides (GPL) were found, evidently due to mutual variations among the three components in GPL (lecithin, cephalin and lysolecithin).
Elevated serum lipids in normal pregnancy have been confirmed by the present study. In normal pregnancy the relative fatty acid composition of serum lecithin was characteristically high in palmitic acid (15:0). From the present knowledge of lipid metabolism in pregnancy there is no obvious explanation for this finding. Furthermore, the serum lecithin relative fatty acid composition mirrored a possible dietary influence with a decrease in the essential fatty acid, linoleic (18:2) and arachidonic (20:4) acids and of the sum of the fatty acid of the linoleic acid series (n-6). This expression for a relative deficiency in essential fatty acids might be due to changes in dietary habits during pregnancy, e.g. an increase in particularly refined carbohydrates. Reciprocal changes in oleic (18:1) and linoleic (18:2) acids further support this suggestion. An expected increase in serum lecithin containing arachidonic acid (20:4)-due to estrogen influence on liver lecithin synthesis-could not be verified in week 34 of the normal pregnancy.
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