Metabolic and endocrine effects of the desogestrel-containing oral contraceptive Mircette

OBJECTIVE: The purpose was to evaluate the metabolic effects of Mircette (brand of desogestrel/ethinyl estradiol and ethinyl estradiol), a low-estrogen, desogestrel-containing oral contraceptive. STUDY DESIGN: Women taking Mircette were evaluated to determine its effects on lipid profiles (n = 74), carbohydrate metabolism (n = 25), and endocrine parameters (n = 53). RESULTS: During cycles 3 and 6 of Mircette treatment, changes from baseline included mean increases in serum triglycerides and very low-density lipoprotein cholesterol ranging between 50% and 60%. Smaller mean increases were observed at these time points in high-density lipoprotein cholesterol subfraction 2 (range between 17% and 25%), total cholesterol (<10%), high-density lipoprotein cholesterol (range between 10% and 15%), and high-density lipoprotein cholesterol subfraction 3 (range between 9% and 13%), with only nominal changes (<6%) in low-density lipoprotein cholesterol and lipoprotein. Patients receiving Mircette showed no mean changes in fasting plasma glucose or serum insulin levels but did have modest increases in glucose and insulin levels after a glucose challenge. Mircette treatment suppressed follicle-stimulating hormone, luteinizing hormone, 17beta-estradiol, and progesterone to levels consistent with inhibition of ovulation and increased concentrations of thyroid- and cortisol-binding globulins. CONCLUSIONS: Overall, Mircette treatment was associated with expected effects on the pituitary-ovarian axis, triglycerides, and serum binding proteins; a modest decline in glucose tolerance; and a favorable effect on lipid profiles as a result of increases in total high-density lipoprotein cholesterol and high-density lipoprotein cholesterol subfraction 2 in the absence of changes in total cholesterol or low-density lipoprotein cholesterol.     

19-Allylaminoherbimycin A, an analog of herbimycin A that is stable against treatment with thiol compounds or granulocyte-macrophage colony-stimulating factor in human leukemia cells

OBJECTIVE: To investigate the effects on lipid and lipoprotein metabolism of two doses (5- or 10 micrograms/24 h) of levonorgestrel released from an intrauterine device (IUD) in combination with orally administered estradiol (2 mg estradiol valerate) in perimenopausal women. DESIGN: A 1-year prospective randomized single blind clinical trial. SETTING: Department of Obstetrics and Gynaecology, Ostra Hospital, G?teborg, Sweden. SUBJECTS: Fifty-one perimenopausal women with climacteric symptoms. OUTCOME MEASURES: Cholesterol in serum and in lipoprotein fractions; high-density lipoprotein (HDL), low-density lipoprotein (LDL). Triglycerides in serum and in very low-density lipoprotein. RESULTS: In both treatment groups significant elevations in HDL-cholesterol of similar magnitude were observed after 1 month and these changes were maintained during the 12 month observation period. In both treatment groups an initial significant decrease of LDL-cholesterol was observed and the decrement was maintained after 12 months. Serum levels of cholesterol decreased significantly in both groups after 1 month and were maintained after 12 months in the levonorgestrel-IUD (LNG-IUD) 5 micrograms group. However, the initial reduction of serum cholesterol in the LNG-IUD 10 micrograms group did not differ from baseline after 12 months. Serum triglyceride levels fluctuated during the observation period. No significant changes occurred. CONCLUSION: Continuous combined HRT with intrauterine administration of levonorgestrel, 5- or 10 micrograms/24 h, in perimenopausal women was observed to increase HDL-cholesterol and to decrease LDL-cholesterol compared with pretreatment values. The low doses of levonorgestrel did not reverse the beneficial effects on lipid metabolism usually seen after estradiol administration.     

Tennis elbow. Current concepts of treatment and rehabilitation

OBJECTIVE: Estrogens are known to exhibit antioxidative effects. At present little information exists on the influence of co-administered progestins upon this effect. Therefore we investigated the influence of levonorgestrel, a potent antiestrogenic progestin, on the inhibition of the low-density lipoprotein (LDL) oxidation by 17 beta-estradiol or 17 beta-estradiol valerate in vitro and ex vivo. METHODS: After isolation from blood, the in vitro oxidation of LDL was induced by copper ions and measured continuously by monitoring the formation of conjugated dienes. In 21 female ovariectomized White New Zealand rabbits the antioxidative action of 17 beta-estradiol alone or in combination with levonorgestrel after subcutaneous infusion for 3 days was determined using the copper-induced LDL-oxidation as an endpoint. Eleven postmenopausal women were exposed to sequential estrogen-progestin replacement therapy (day 1-21:2 mg estradiol valerate/day, day 10-21: 0.15 mg levonorgestrel/day). Blood samples were collected at three times: on day 1, on day 10, on day 22 (after the combination phase). The lag time of ex vivo oxidation of LDL, the plasma estradiol and estrone levels were estimated. RESULTS: In the chosen cell-free system, 17 beta-estradiol increased the lag time of the LDL-oxidation in a dose-dependent manner. Levonorgestrel showed neither pro-oxidative nor antioxidative effects when administered alone in different concentrations. Co-administration of different doses of levonorgestrel did not modify the antioxidative action of estrogen either. The two ex-vivo models confirmed these results. In rabbits the co-administered 19-nortestosterone derivative levonorgestrel did not impair or reverse the estradiol-dependent effect. In postmenopausal women the daily oral administration of levonorgestrel in conjunction with 17 beta-estradiol valerate did not diminish the antioxidative action of this estrogen given for the first 9 days. CONCLUSION: The antioxidative potential of estradiol and estradiol valerate is maintained in the presence of levonorgestrel.     

Asymmetrical hemispheric activation and behavioral persistence: effects of unilateral muscle contractions

OBJECTIVE: To compare pubertal maturation, sex steroid hormones, and lipoproteins and their interrelationships in male offspring of parents with premature coronary heart disease (cases) and a control group. DESIGN: This was a cross-sectional comparison of cases and members of a control group 10 to 15 years of age. SUBJECTS AND METHODS: Offspring were recruited from patient lists of area physicians. Members of the control group were recruited from area schools. Body mass (kg/m2), serum lipids, lipoproteins, apolipoproteins, estradiol, and free testosterone were measured. RESULTS: Differences in age were not significant, but offspring were taller, heavier, and more mature. Offspring had higher total and low density lipoprotein cholesterol. Offspring had lower estradiol levels in early puberty but higher levels in late puberty. With family history and body mass in the regression models for lipid parameters, free testosterone was a significant explanatory factor for total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein, and estradiol was a significant predictor for apolipoprotein B. The percent of the variance in the lipid parameters explained by testosterone and estradiol was small. CONCLUSION: Sex hormone concentrations appear to be modest but significant predictors of lipoprotein and apolipoprotein concentrations in offspring and a control group in cross-sectional analysis. After controlling for pubertal maturation, hormone and lipid concentrations differed in offspring and the control group.     

Relationship between acute diarrhoea and low plasma levels of vitamin A and retinol binding protein

OBJECTIVE: We studied possible sex differences of the effect of fenofibrate on serum lipoproteins. Twenty-three patients with primary hypercholesterolaemia (10 postmenopausal women and 13 aged-matched men) were treated with slow-release fenofibrate for 96 weeks. RESULTS: Steady state lipoprotein concentrations were reached after 12 and 24 weeks of treatment in women and men, respectively. During the subsequent follow-up the lipoprotein concentrations remained constant. In women total and low-density lipoprotein (LDL) cholesterol decreased from 299 to 234 mg.dl-1 and from 210 to 151 mg.dl-1, respectively, and in men from 265 to 233 mg.dl-1 and from 192 to 160 mg.dl-1. The decrease in triglycerides was also more pronounced in women (-42%) than in men (-18%). High-density lipoprotein (HDL) cholesterol increased significantly in women from 53 to 63 mg.dl-1 but not in men (45 to 50 mg.dl-1). Since the changes in LDL and HDL cholesterol occurred in opposite directions, the decrease in LDL/HDL cholesterol ratio was accentuated in both groups. However, this ratio was decreased almost twofold in women (-41%) compared to men (-23%). Although the serum concentrations of fenofibric acid were 1.3-fold higher in women than in men, which was probably due to the higher body weight in men (1.2-fold), this difference can hardly explain the favorable effect on lipoproteins in women. CONCLUSION: The present study indicates that fenofibrate might be very effective by reducing the concentrations of atherogenic lipoproteins in postmenopausal women.     

Antiatherogenic effects of adjuvant antiestrogens: a randomized trial comparing the effects of tamoxifen and toremifene on plasma lipid levels in postmenopausal women with node-positive breast cancer

PURPOSE: To evaluate whether a novel antiestrogen, toremifene, has similar antiatherogenic effects as tamoxifen. PATIENTS AND METHODS: Forty-nine postmenopausal patients with node-positive breast cancer were randomized in a trial that compared the effects of tamoxifen and toremifene on serum lipoproteins. Tamoxifen was given at 20 mg and toremifene at 60 mg orally per day for 3 years. Serum concentrations of apolipoprotein (apo) A-I, A-II, and B, and lipoprotein(a) [Lp(a)], cholesterol, triglyceride, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol were measured before and after 12 months of antiestrogen therapy. RESULTS: Both antiestrogens significantly reduced serum total and LDL cholesterol and apo B levels. However, the response of HDL cholesterol to treatments was clearly different between the groups. Toremifene increased the HDL level by 14%, whereas tamoxifen decreased it by 5% (P = .001). As a consequence, both cholesterol-to-HDL and LDL-to-HDL ratios decreased more in the toremifene than tamoxifen group (P = .008 and P = .03, respectively). Toremifene also increased the apo A-I level (P = .00007) and apo A-I-to-A-II ratio (P = .018). Both tamoxifen and toremifene decreased the Lp(a) concentration significantly (change, 34% v 41%). CONCLUSION: These results provide positive evidence that toremifene has antiatherogenic properties with potency to improve all lipoproteins that are associated with increased coronary heart disease (CHD) risk.     

17beta-Estradiol, progesterone, and testosterone inversely modulate low-density lipoprotein oxidation and cytotoxicity in cultured placental trophoblast and macrophages

OBJECTIVES: We have previously shown that low-density lipoprotein oxidation is diminished by 17beta-estradiol and enhanced by progesterone and testosterone. In these experiments we wished to learn whether sex hormone effects on low-density lipoprotein oxidation alter placental cell viability in primary tissue culture. STUDY DESIGN: Primary tissue culture of human term placental cells was performed. RESULTS: Addition of 17beta-estradiol decreased low-density lipoprotein oxidation (measured as lipid peroxides, thiobarbituric acid-reacting substances, and low-density lipoprotein electrophoretic mobility) and placental cell toxicity (measured as chromium 51 release) with maximum reductions of 28% (macrophages) (p < 0.05) and 26% (trophoblasts) (p < 0.01). Conversely, progesterone and testosterone increased low-density lipoprotein oxidation and chromium 51 release, the latter a maximum of 28% and 18%, respectively, for progesterone and testosterone in macrophages (p < 0.05 in both instances) and 23% in trophoblasts (p < 0.05, testosterone only). Collectively, cytotoxicity was proportional to low-density lipoprotein oxidation and estradiol, progesterone, and testosterone concentrations. CONCLUSIONS: Estradiol inhibits placental macrophage- and trophoblast-mediated low-density lipoprotein oxidation and cytotoxicity, whereas progesterone and testosterone promote these effects. Sex steroid hormones may modulate the effects of oxidative stress on placental function in pregnancy.     

Effects of docosahexaenoic acid on serum lipoproteins in patients with combined hyperlipidemia: a randomized, double-blind, placebo-controlled trial

OBJECTIVE: The objective of this study was to evaluate the effects of daily dietary supplementation with 1.25 g or 2.5 g of docosahexaenoic (DHA), in the absence of eicosapentaenoic acid (EPA), on serum lipids and lipoproteins in persons with combined hyperlipidemia (CHL) [serum low-density lipoprotein cholesterol (LDL-C) 130 to 220 mg/dL and triglycerides 150 to 400 mg/dL]. METHODS: After a 6-week dietary stabilization period, subjects entered a 4-week single-blind placebo (vegetable oil) run-in phase. Those with adequate compliance during the the run-in were randomized into one of three parallel groups (placebo, 1.25, or 2.5 g/day DHA) for 6 weeks of treatment. Supplements were administered in a triglyceride form contained in gelatin capsules. Primary outcome measurements were plasma phospholipid DHA content, serum triglycerides, high-density lipoprotein cholesterol (HDL-C). LDL-C and non-HDL-C. RESULTS: The DHA content of plasma phospholipids increased dramatically (2 to 3 fold) in a dose-dependent manner. Significant (p < 0.05) changes were observed in serum triglycerides (17 to 21% reduction) and HDL-C (6% increase) which were of similar magnitude in both DHA groups. Non-HDL-C [+1.6 (NS) and +5.7% (p < 0.04)] and LDL-C [+9.3% (NS) and +13.6% (p < 0.001)] increased in the DHA treatment groups. All lipid effects reached an apparent steady state within the first 3 weeks of treatment. CONCLUSION: Dietary DHA, in the absence of EPA, can affect lipoprotein cholesterol and triglyceride levels in patients with combined hyperlipidemia. The desirable triglyceride and HDL-C changes were present at a dose which did not significantly increased non-HDL-C or LDL-C. These preliminary findings suggest that dietary supplementation with 1.25 g DHA/day, provided in a triglyceride form, may be an effective tool to aid in the management of hypertriglyceridemia.     

Effects of estrogen replacement therapy on the lipoprotein profile in postmenopausal women with ESRD

BACKGROUND: Patients with ESRD have excessive cardiovascular morbidity and mortality. In postmenopausal women with normal renal function, estrogen replacement therapy decreases cardiovascular mortality by 50%, in part because of their beneficial effects on the lipoprotein profile. Because of similarities in the lipoprotein profile between healthy, postmenopausal women, and women with ESRD, we examined the effects of estrogen replacement on lipoproteins in 11 postmenopausal women with ESRD. METHODS: In a randomized, placebo-controlled crossover study (8 week treatment arms) using 2 mg daily of oral, micronized estradiol, 11 postmenopausal women with ESRD were treated. Neither baseline lipid nor lipoprotein abnormalities were used as entry criteria for study participation. RESULTS: Blood estradiol levels were 19 +/- 4 with placebo and 194 +/- 67 pg/ml (P = 0.024) with estradiol treatment. Total HDL cholesterol concentrations increased from 52 +/- 19 mg/dl to 61 +/- 20 mg/dl (16%), with placebo and estradiol treatments, respectively (P = 0.002). Apolipoprotein A1 increased by 24.6% (P = 0.0002) with estradiol intervention. HDL2 concentrations were 19 +/- 13 with placebo and 24 +/- 16 with estradiol treatment (P = 0.046). There were no differences in total or LDL cholesterol, other lipoprotein fractions including Lp(a), and triglycerides with 2 mg daily estradiol treatment. No significant side effects were observed. CONCLUSIONS: Therefore, using standard dosage regimens for estrogen replacement therapy in postmenopausal women with ESRD, HDL cholesterol is increased to an extent that would be expected to improve their cardiovascular risk profile. Further studies are needed to assess whether estrogen replacement therapy decreases the incidence or severity of cardiovascular disease in ESRD patients to a similar degree compared with other women.     

The use of an interactive computer program for the education of parents of asthmatic children

OBJECTIVES: To evaluate the effect of a single evening meal (gorging) on plasma lipids and lipoproteins in normal individuals observing the Ramadan Fast. During the Ramadan month, Muslims refrain from food and liquids during the day and eat a large meal after sundown. DESIGN: Sequential measurement of plasma lipids and lipoproteins in Muslims observing the Ramadan Fast and non-fasting individuals. SETTING: The study was conducted in the Bedouin town of Rahat, in the northern Negev area of Israel. SUBJECTS: Twenty-two healthy subjects who fasted during Ramadan and 16 non-fasting laboratory workers, were studied before Ramadan, at week 1, 2 and 4 of the Ramadan month, and again four weeks after the end of Ramadan. RESULTS: Plasma high-density lipoprotein cholesterol (HDL) rose significantly (P < 0.001) at the week 4 measurement, returning to basal levels 4 weeks after the end of Ramadan. Total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL), very-low density lipoprotein cholesterol (VLDL), and lipoprotein (a) [Lp(a)] did not change significantly. CONCLUSIONS: Plasma HDL increased by 23% after four weeks of gorging. The dietary change did not affect the composition of other lipoproteins, such as LDL, VLDL or Lp(a), other plasma biochemical parameters, or BMI. Prolonged gorging, well tolerated by all individuals, is a very effective non-pharmacological method to increase plasma HDL-cholesterol.     

Comparative effects of atenolol versus celiprolol on serum lipids and blood pressure in hyperlipidemic and hypertensive subjects

Antihypertensive drugs may affect serum lipoprotein levels in mixed populations but data in hyperlipidemic patients are scanty. Atenolol versus celiprolol effects on serum lipoproteins were compared in 159 hyperlipoproteinemic hypertensive patients. This was a randomized, double-blind, parallel-group, positive-controlled multicenter trial with centralized lipoprotein laboratory and diet constancy monitoring. Blood pressure reduction and serum lipoprotein and apoprotein levels were monitored for 3 months. Both drugs reduced systolic and diastolic blood pressures. Atenolol had greater effects than celiprolol on diastolic pressure, but effects on systolic blood pressure were not different. Patients receiving atenolol had lower serum high-density lipoprotein cholesterol levels and higher low-density lipoprotein/high-density lipoprotein cholesterol ratios, whereas patients treated with celiprolol showed no contrasting changes. These differences in lipoprotein levels between drug treatment groups were statistically significant at weeks 9 and 12. The difference between drug treatments was also significant if the values of the 9- and 12-week visits were averaged. Patients taking atenolol had statistically significantly higher serum levels of total cholesterol, triglycerides and apoprotein B at 9 weeks. These divergent directional changes were consistent throughout and statistically significantly different between drugs.     

Delaware RNs'' reasons for nonparticipation in continuing education

BACKGROUND: Acipimox, a derivative of nicotinic acid, lowers serum lipid levels by reducing the production of very-low-density and low-density lipoproteins (LDL). METHODS: We studied the additional lipid-lowering effect of high doses of acipimox in 12 patients with severe familial hypercholesterolemia (FH) who were on treatment with an HMG CoA reductase inhibitor, in some cases in combination with a resin. RESULTS: There was a significant reduction in total serum cholesterol (-9%), LDL-cholesterol (-9%) and serum triglycerides (-21%) when the standard doses of acipimox (750 mg/day) was added to treatment with simvastatin (and a resin). However, higher doses had no further hypolipidemic effect. In concordance with the reduction of serum cholesterol and LDL-cholesterol there was a significant decrease in apolipoprotein (apo)-B (-11%). There was no change in HDL-cholesterol, apo-A1 and lipoprotein(a). Acipimox in high doses up to 2250 mg/d was well tolerated except for initial gastric complaints and of flushing; because of these side effects one patient dropped out of the study. CONCLUSIONS: Acipimox in high doses, which were well tolerated, has no additional lowering effect on LDL-levels compared to the standard dose in patients with severe FH who are already treated with simvastatin.     

Intrauterine contraceptive devices. Mode of action, experiences, complications (author''s transl)

Effects of norethisterone (NT) purified norethisterone (pure NT), norethynodrel (NE), medroxyprogesterone acetate (MAP), chlormadinone acetate (CMA) and desoxycorticosterone acetate (DOCA) on serum and liver lipid levels and serum lipoproteins were examined in both intact and estradiol-treated male rats. NT and NE caused a decrease in serum cholesterol and phospholipid levels, an increase in liver cholesterol level, no significant change in triglyceride levels of both serum and liver, with a significant change in serum lipoprotein patterns; a decreased in alpha- and beta-lipoproteins and a marked increase in pre beta-lipoprotein. Pure NT decreased serum cholesterol without causing any change in lipoprotein pattern. MAP, CMA and DOCA causee almost no effect on lipid levels in serum and liver, but CMA and DOCA increased alpha-lipoprotein and decreased beta- and pre beta-lipoproteins. An acute treatment with estradiol caused a decrease in alpha- and beta-lipoproteins and an increase in pre beta-lipoprotein with a decrease in serum lipid levels and an increase in liver lipids. By contrary, a chronic treatment with a marked hypercholesterolemia. This increase of alpha-lipoprotein in estradiol-treated rats was prevented by NT and NE, not affected or rather decreased by MAP but further increased with CMA and DOCA. These data suggest that the effects of synthetic progestational steroids on lipids are classified into two groups, 19-nortestosterone derivatives and 17alpha-hydroxyprogesterone derivatives including DOCA. The former caused a decrease in serum lipid levels with an increase of pre beta-lipoprotein and adecrease of alpha-lipoprotein. The latter caused almost no change or a slight increase in serum lipid levels with a decrease in pre beta-lipoprotein and an increase in alpha-lipoprotein, though it was not found in MAP.     

Lipoprotein composition in the insulin-deficient non-acidotic phase of type I diabetic patients and early evolution after the start of insulin therapy

Lipoproteins, including intermediate density lipoproteins and lipoprotein(a), and apolipoproteins A-I, B, C-II, C-III and E, were studied in 13 newly-diagnosed type I diabetic patients with severe insulinopenia without dehydration or acidosis. At baseline, the main finding was a significant increase in serum triglycerides due to raised triglyceride concentrations in all lipoproteins, particularly triglyceride-rich lipoproteins. Cholesterol concentrations were slightly increased in lipoproteins and led to a significant increase in serum cholesterol. Two days after the start of insulin therapy, lipoprotein profiles had normalized except for the LDL triglyceride contents, which remained significantly increased on the fifth day of treatment. No significant modifications were observed in lipoprotein(a), apolipoproteins A-I and E concentrations throughout the study. However, serum apolipoproteins B, C-II and C-III were increased at baseline and fell to normal levels 2 days after the start of insulin therapy. On the other hand, apolipoprotein C-II/C-III ratios in high and very low density lipoprotein, showed no significant differences at baseline compared with controls, suggesting that an apolipoprotein C-II deficiency or apolipoproteins Cs imbalance can be ruled out. In conclusion, significant lipoprotein abnormalities were observed in the insulin-deficient state of type I diabetes mellitus; insulin therapy normalizes the lipoprotein profile in two days, except for low density lipoprotein triglyceride contents which remain increased at the fifth day.     

Continuous combined hormone replacement therapy compared with tibolone

OBJECTIVE: To compare relief of vasomotor symptoms, changes in lipoproteins, and bleeding patterns in postmenopausal women receiving either continuous combined hormone replacement therapy (HRT) of estradiol valerate and norethisterone or tibolone 2.5 mg/day. METHODS: In a multicenter, randomized, open-label study, 235 postmenopausal women received one of the above-mentioned treatments. Fasting lipoproteins were measured at baseline and at 3, 6, and 12 months. At each visit, participants completed Greene climacteric questionnaires and recorded any bleeding episodes. Data are presented as mean +/- standard deviation if normally distributed, median and interquartile range if non-normally distributed, or as frequency count. For menopausal symptoms and diary card data, the differences were tested by Wilcoxon rank-sum test. RESULTS: One hundred sixteen women received continuous combined HRT and 119 women received tibolone; 72 and 76 women, respectively, completed 12 months of therapy. Both treatments effectively relieved vasomotor symptoms and reduced serum total cholesterol. Continuous combined HRT, but not tibolone, significantly reduced low-density lipoprotein levels. Both treatments reduced high-density lipoprotein levels, but the effect was more profound with tibolone. The initial bleeding score was higher for women taking continuous combined HRT; however, by the end of the study, the percentages of amenorrheal women were comparable. Endometrial histology was similar for both treatments at the end of the study, although two cases of proliferative endometrium were found in the tibolone group. CONCLUSION: Estradiol valerate-norethisterone continuous combined HRT controls symptoms and is associated with a safe lipid profile.     

Identification and subcellular localization of a novel mammalian dynamin-related protein homologous to yeast Vps1p and Dnm1p

OBJECTIVE: To study the differential effects of subcutaneous E2 alone or in combination with P on the susceptibility of low-density lipoprotein (LDL) cholesterol to oxidation in naturally postmenopausal diet-controlled rhesus monkeys. DESIGN: Prospective, longitudinal controlled study. SETTING: Oregon Health Sciences University, Portland, Oregon, and Oregon Regional Primate Research Center, Beaverton, Oregon. PATIENT(S): Five naturally postmenopausal rhesus monkeys. INTERVENTION(S): Estradiol was administered subcutaneously for the first 4 weeks, followed by E2 plus P for 4 weeks, followed by a third 4-week washout period. MAIN OUTCOME MEASURE(S): Changes in plasma lipoprotein levels and oxidation of LDL and serum concentrations of E2 and P. RESULT(S): Levels of LDL cholesterol fell after 4 weeks of treatment with E2, compared with baseline. The lag time to half maximal light absorbancy after 4 weeks of E2 treatment was significantly increased compared with baseline. The maximal absorbance values and the slope of the propagation phase after 4 weeks of treatment with E2 were decreased compared with baseline. After 4 weeks of combined E2 and P treatment, all values were comparable to baseline. CONCLUSION(S): These results suggest that subcutaneous E2 therapy appears to enhance LDL resistance to oxidation and that this effect is attenuated by the addition of the P.     

Cloning of a mouse smoothened cDNA and expression patterns of hedgehog signalling molecules during chondrogenesis and cartilage differentiation in clonal mouse EC cells, ATDC5

The effects of simvastatin and pravastatin administered alone at initial doses of 5 and 10 mg/day, respectively, on normalization of abnormal lipid metabolism in patients with hypercholesterolemia were evaluated by a crossover method. Patients whose serum levels of total cholesterol (TC) were > or = 220 mg/dl were randomly divided into two groups, and one of the groups (group S-P: 17 patients) was treated with simvastatin first and then with pravastatin whereas the other group (group P-S: 19 patients) was treated with pravastatin first and then with simvastatin. Simvastatin or pravastatin was replaced with the other drug after 8-week administration in each group. These drugs were administered for 8 weeks each. Simvastatin and pravastatin significantly reduced the following serum lipids as compared with the levels in the observation period: TC by 23.2 +/- 8.1% and 18.1 +/- 10.9%, triglyceride (TG) by 13.0 +/- 24.7% and 5.8 +/- 47.1%, and low-density lipoprotein cholesterol (LDL-C) by 31.3 +/- 10.1% and 23.1 +/- 14.3%, respectively. TC and LDL-C levels were significantly (p < 0.001) lower and decreased to significantly (p < 0.001) greater degrees after simvastatin treatment than after pravastatin treatment. TC was normalized in 77.8% of the patients (28 of 36) after simvastatin treatment and in 68.9% of the patients (23 of 36) after pravastatin treatment. LDL-C was normalized in 63.9% of the patients (23 of 36) after simvastatin treatment and in 44.4% of the patients (16 of 36) after pravastatin treatment. The percentage of patients whose LDL-C was normalized by simvastatin was significantly (p < 0.05) higher as compared with pravastatin. Results of this trial, which was conducted by a crossover method, show that the initial dose of simvastatin reduces serum cholesterol and LDL-C more potently than the initial dose of pravastatin in patients with hypercholesterolemia.     

The effect of percutaneous oestrogen replacement therapy on Lp(a) and other lipoproteins

OBJECTIVES: To determine the effect of percutaneous oestrogen replacement therapy on lipoprotein (a) and other plasma lipoproteins. METHODS: Open longitudinal prospective study conducted at the hormone replacement clinic of the Prince of Wales Hospital, New Territories, Hong Kong. Thirty women who had undergone a total abdominal hysterectomy and bilateral salpingo-oophorectomy for benign gynaecological conditions were treated with 1.5 mg of percutaneous 17 beta-oestradiol gel applied daily for a period of 12 consecutive months. Measurements of plasma lipoproteins were made before the commencement of treatment and repeated at 6- and 12-month intervals. RESULTS: There was a significant reduction in the concentrations of Lp(a) during the first 6 months of treatment, with median values falling from 7.87 mg dL-1 to 6.16 mg dL-1 (P = 0.004, 0-6 months). During the second 6 months, the median concentration increased to 9.38 mg dL-1, (P = 0.072, 6-12 months), which did not significantly differ from the baseline level (P = 0.545, 0-12 months). Significant reductions in the concentrations of apoprotein A-I (apo A-I), apoprotein B (apo B), high density lipoprotein cholesterol (HDL-C), and HDL3-C were also present after 6 months (P = 0.043, 0.049, 0.028, 0.013, respectively), but there were no differences between the baseline values of these lipoproteins and those at the completion of the study (P = 0.948, 0.244, 0.839, 0.117 respectively). Drug compliance was maintained throughout the study, with similar mean oestradiol concentrations at 6 and 12 months. CONCLUSIONS: The percutaneous administration of 17 beta-oestradiol has variable short term effects on plasma lipoproteins which are not maintained over a longer duration of treatment. By avoiding the 'first pass' effect on the liver, this method of delivery does not appear to produce the sustained changes in lipoproteins seen with oral treatment.     

Impact of apolipoprotein E polymorphism on lipoproteins and risk of myocardial infarction. The ECTIM Study

Human apolipoprotein (apo) E, a polymorphic protein with three common alleles, epsilon 2, epsilon 3, and epsilon 4, plays an important role in lipoprotein metabolism. This article describes the association of this polymorphism with lipids, apolipoproteins, and lipoproteins with a particular regard to lipoprotein particles, as defined by their apolipoprotein content, as well as the risk of myocardial infarction in a multicenter population-based case-control study (ECTIM study). In the ECTIM study, 574 male patients aged 25 to 64 were examined 3 to 9 months after myocardial infarction in four regions participating in the World Health Organization MONICA project: Belfast (Northern Ireland) and Lille, Strasbourg, and Toulouse (France). Control subjects (n = 722) were randomly selected from the regional populations. The distribution of apoE phenotypes was significantly different across the four control samples (P = .04), with a higher frequency of the epsilon 4 allele in Belfast (14.3%) than in Toulouse (8.2%). The association of apoE polymorphism with biological measurements was studied in the control groups (n = 640) after men with coronary heart disease or those taking hypolipidemic drugs were omitted, with the apoE3/3 phenotype as a reference after adjustment for concomitant factors. Individuals carrying the epsilon 2 allele had lower levels of plasma cholesterol, low-density lipoprotein cholesterol (LDL-C), and apoB and higher levels of triglycerides, very-low-density lipoprotein cholesterol (VLDL-C), apoC-III, apoE, lipoprotein (Lp) C-III:B, and Lp E:B. However, the effect of the epsilon 2 allele on triglyceride, VLDL-C, apoE, and Lp E:B parameters was heterogeneous across the populations.(ABSTRACT TRUNCATED AT 250 WORDS)