Fatty acid composition of lizard tissue lipids and the effects of estradiol on serum free fatty acids

Fatty acid analyses of lipids from lizard fat bodies, carcass, and blood serum were performed by GLC. Principal fatty acids from all three tissues were palmitate (16:0), stearate (18:0), oleate (18:1), and linoleate (18:2). Administration of estradiol to vitellogenic or non-vitellogenic lizards increased serum levels of non-esterified fatty acids, but had no effect on the fat body wet weights. Lizards receiving estradiol had a higher proportion of arachidonate and a lower proportion of oleate in their serum non-esterified fatty acids.     

Determination of estradiol valerate in pharmaceutical preparations and human serum by flow injection chemiluminescence

A novel method for the detection of trace estradiol valerate (EV) in pharmaceutical preparations and human serum was developed by inhibition of luminol chemiluminescence (CL) by estradiol valerate on the zinc deuteroporphyrin (ZnDP)‐enhanced luminol‐K₃Fe(CN)₆ chemiluminescence system. Under optimized experimental conditions, CL intensity and concentration of estradiol valerate had a good linear relationship in the ranges of 8.0 × 10^‐8 to 1.0 × 10^‐5 g/mL. Detection limit (3σ) was estimated to be 3.5 × 10^‐8 g/mL. The proposed method was applied successfully for the determination of estradiol valerate in pharmaceutical preparations and human serum and recoveries were 97.0‐105.0% and 95.5‐106.0%, respectively. The possible mechanism of the CL system is discussed. Copyright © 2012 John Wiley & Sons, Ltd.     

Beneficial effects of diclofenac therapy on serum lipids, oxidized low-density lipoprotein and antioxidant defenses in rats

To study the effects of diclofenac, a nonselective nonsteroidal anti-inflammatory drug (NSAID), on lipid profile, oxidized low-density-lipoprotein (Ox-LDL), serum antioxidant defenses and markers of oxidative stress, male Wistar rats were divided into two groups (n=10): (C) receiving intramuscularly a single daily dose of saline (NaCl 0.9%), and (AI) receiving intramuscularly a single daily dose of 10 mg/kg diclofenac sodium (C14H10Cl2NNaO2). After 28 days diclofenac-treated rats had lower Ox-LDL, apoprotein B (apo-B), apo-B/LDL-cholesterol and lipid hydroperoxide than C. Total antioxidant substances and superoxide dismutase were increased in diclofenac-treated rats, while no significant changes were observed in catalase, glutathione peroxidase and nitric oxide. A perincubation test done to examine the possibility of mechanism-based activation showed that diclofenac had no effect on maximal superoxide dismutase velocity, but significantly reduced the Michaelis-Menten (KM) constant, indicating that diclofenac induced SOD activation increasing substrate linkage affinity to the enzyme-catalytic site. In conclusion, diclofenac had beneficial effects decreasing Ox-LDL and improving antioxidant defense. It appears that the application of this agent may be feasible and beneficial for serum antioxidant protection, which certainly would bring new insights on dyslipidemia control.     

The effects of 20 days bed rest on serum lipids and lipoprotein concentrations in healthy young subjects

The effects of 20 days bed rest (BR) on serum lipids and lipoprotein concentrations were investigated in 23 healthy young subjects (13 males and 10 females, aged 19 to 25 yr.). After 20 days BR, VO2max was reduced in both genders, but body composition did not change. The ratio of glucose area to insulin area during an oral glucose tolerance test decreased gradually throughout BR, which suggested a decrease in insulin sensitivity. Estimated changes in plasma volume from the beginning of BR were largest at day 3 of BR (-9.1% in females and -3.4% in males) and seemed to return the initial level at the end of BR in both genders. The increase in serum triglycerides and the decrease in high density lipoprotein (HDL) cholesterol, and apolipoprotein AI were observed in both genders during BR. In a smaller study of 4 males and 5 females, 20 days BR was associated with a decrease in HDL, cholesterol, a decrease in apolipoprotein AI and apolipoprotein AII, decrease in a plasma postheparin lipoprotein lipase activity and an increase in very low density lipoprotein triglyceride. Overall, the data suggested that the decrease in lipoprotein lipase activity and insulin sensitivity may contribute to the impairment in HDL metabolism.     

Pharmacokinetics and biotransformation of estradiol valerate in ovariectomized women

Estradiol valerate is well suited for treatment of the characteristic symptoms accompanying menopause in women. The pharmacokinetics and biotransformation of estradiol valerate were studied in women following intravenous, intramuscular and oral administration. Intravenously given, estradiol valerate is split by enzymatic hydrolysis into 17 beta-estradiol and the fatty acid. The estrogen arising in vivo from the steroid ester is subject to intermediate metabolism. The metabolites are eliminated at a nearly constant rate mainly in urine. The biotransformation of estradiol valerate was not different following intravenous or intramuscular injection. Orally given estradiol valerate is subject to an extensive first pass metabolism. Daily repeated oral administration does not result in accumulation of 17 beta-estradiol and its metabolites.     

Effect of estradiol valerate on ovarian follicle dynamics and superovulatory response in progestin-treated cattle

Three experiments evaluated the effects of estradiol valerate (EV) on ovarian follicular and CL dynamics, intervals to estrus and ovulation, and superovulatory response in cattle. Experiment 1 compared the efficacy of two norgestomet ear implants (Crestar and Syncro-Mate B; SMB) for 9 d (with PGF at implant removal), combined with either 5 mg estradiol-17beta and 100 mg progesterone (EP) or 5 mg EV and 3mg norgestomet (EN) im at the time of implant insertion on CL diameter and follicular wave dynamics. Ovaries were monitored by ultrasonography. There was no effect of norgestomet implant. Diameter of the CL decreased following EN treatment (P < 0.01). Mean (+/- S.D.) day of follicular wave emergence (FWE) was earlier (P < 0.0001) and less variable (P < 0.0001) in EP- (3.6 +/- 0.5 d) than in EN- (5.7 +/- 1.5 d) treated heifers. Intervals from implant removal to estrus (P < 0.001) and ovulation (P < 0.01) were shorter in EN- (45.7 +/- 11.7 and 74.3 +/- 12.6 h, respectively) than in EP- (56.4 +/- 14.1 and 83.3 +/- 17.0 h, respectively) treated heifers. Experiment 2 compared the efficacy of EP versus EN in synchronizing FWE for superovulation in SMB-implanted cows. At random stages of the estrous cycle, Holstein cows (n = 78) received two SMB implants (Day 0) and were randomly assigned to receive EN on Day 0 or EP on Day 1. Folltropin-V treatments were initiated on the evening of Day 5, with PGF in the morning and evening of Day 8, when SMB were removed. Cows were inseminated after the onset of estrus and embryos were recovered 7 d later. Non-lactating cows had more CL (16.7 +/- 11.3 versus 8.3 +/- 4.9) and total ova/embryos (14.7 +/- 9.5 versus 7.9 +/- 4.6) than lactating cows (P < 0.05). EP-treated cows tended (P = 0.09) to yield more transferable embryos (5.6 +/- 5.2) than EN-treated cows (4.0 +/- 3.7). Experiment 3 compared the effect of dose of EV on ovarian follicle and CL growth profiles and synchrony of estrus and ovulation in CIDR-treated beef cows (n = 43). At random stages of the estrous cycle (Day 0), cows received a CIDR and no further treatment (Control), or an injection of 1, 2, or 5 mg im of EV. On Day 7, CIDR were removed and cows received PGF. Follicular wave emergence occurred within 7 d in 7/10 Control cows and 31/32 EV-treated cows (P < 0.05). In responding cows, interval from treatment to FWE was longer (P < 0.05) in those treated with 5 mg EV (4.8 +/- 1.2 d) than in those treated with 1 mg (3.2 +/- 0.9 d) or 2 mg (3.4 +/- 0.8 d) EV, while Control cows were intermediate (3.8 +/- 2.0 d). Diameter of the dominant follicle was smaller (P < 0.05) at CIDR removal and tended (P = 0.08) to be smaller just prior to ovulation in the 5 mg EV group (8.5 +/- 2.2 and 13.2 +/- 0.6 mm, respectively) than in the Control (11.8 +/- 4.6 and 15.5 +/- 2.9 mm, respectively) or 1mg EV (11.7 +/- 2.5 and 15.1 +/- 2.2 mm, respectively) groups, with the 2mg EV group (10.7 +/- 1.5 and 14.3 +/- 1.7 mm, respectively) intermediate. Diameter of the dominant follicle at CIDR removal was less variable (P < 0.01) in the 2 and 5mg EV groups than in the Control group, and intermediate in the 1mg EV group. In summary, treatment with 5mg EV resulted in a longer and more variable interval to follicular wave emergence than treatment with 5mg estradiol-17beta, which affected preovulatory dominant follicle size following progestin removal, and may have also affected superstimulatory response in Holstein cows. Additionally, 5 mg EV appeared to induce luteolysis in heifers, reducing the interval to ovulation following norgestomet removal. Conversely, intervals to, and synchrony of, follicular wave emergence, estrus and ovulation following treatment with 1 or 2 mg EV suggested that reduced doses of EV may be more useful for the synchronization of follicular wave emergence in progestogen-treated cattle.     

Influence of contraceptive pill and menstrual cycle on serum lipids and high-density lipoprotein cholesterol concentrations.

The fluctuations of serum lipid and lipoprotein concentrations within one cycle were studied both in women using and not using oral contraceptives. High-density lipoprotein cholesterol decreased significantly from 1.47 mmol/l (57 mg/100 ml) to 1.30 mmol/l (50 mg/100 ml) during one contraceptive cycle in eight women and rose again to the initial value during the pill-free days. The mean concentration of total cholesterol also fell significantly as a result of the decrease of high-density lipoprotein cholesterol and of a not significant decrease of low-density lipoprotein cholesterol. The mean serum triglyceride concentration did not change significantly. The fluctuations in the concentration of serum lipids and lipoproteins in 10 women not using oral contraceptives were smaller than in the women using oral contraceptives and no significant changes in the concentrations were found during one cycle. Thus, high-density lipoprotein cholesterol concentration decreases during each contraceptive cycle. The time of blood sampling during the cycle is, therefore, of vital importance in interpreting the effect of oral contraceptives on high-density lipoprotein cholesterol. In women not using oral contraceptives blood can be sampled on random days during the cycle.     

An overview of the development of combined oral contraceptives containing estradiol: focus on estradiol valerate/dienogest

Natural estrogens such as estradiol (E(2)) or its valerate ester (E(2)V) offer an alternative to ethinyl estradiol (EE). E(2)-containing combined oral contraceptives (COCs) have demonstrated sufficient ovulation inhibition and acceptable contraceptive efficacy. However, earlier formulations were generally associated with unacceptable bleeding profiles. Two E(2)V-containing preparations have been approved to date for contraceptive use: E(2)V/cyproterone acetate (CPA) (Femilar(?); only approved in Finland and only in women >40 years or women aged 35-40 years in whom a COC containing EE is not appropriate) and E(2)V/dienogest (DNG; Qlaira(?)/Natazia(?)). The objective of the current review is to provide an overview of the development of COCs containing natural estrogen, highlighting past issues and challenges faced by earlier formulations, as well as the current status and future directions. The majority of information to date pertains to the development of E(2)V/DNG.     

Oxidized lipoprotein lipids and atherosclerosis

Plasma lipoproteins contain variable amounts of lipid oxidation products (LOP), which are known to impair normal physiological functions and stimulate atherosclerotic processes. Recent evidence indicates that plasma lipoproteins are active carriers of LOP, low-density lipoprotein (LDL) directing transport toward peripheral tissues, and high-density lipoprotein (HDL) being active in the reverse transport. It has been proposed that the lipoprotein-specific transport of LOP could play a role in atherosclerosis-related effects of LDL and HDL. This article gives an overview of the present knowledge of lipoprotein LOP transport and its association with the risk of atherosclerosis and cardiovascular diseases (CVD). Evidence of the significance of lipoprotein LOP transport comes mainly from studies of physiological oxidative stress and is supported by studies of the functionality apolipoprotein A-1 mimetic peptides. A large body of data has accumulated indicating that lipoprotein LOP transport is connected to the risk of atherosclerosis. While high levels of LOP carried by LDL are indicative of elevated risk, high LOP level in HDL appears to associate with protection. If confirmed, the proposed lipoprotein LOP transport function would affect conception of the etiology of atherosclerosis, but would not conflict current views of the pathophysiological mechanisms. It could open new perspectives, such as the dietary origin of LOP, and the protective function of HDL in clearance of LOP. Focusing on LOP could give additional tools especially for prevention and diagnosis, but would not radically change the management of atherosclerosis and CVD.     

Endometrial development and adenogenesis in the neonatal pig: effects of estradiol valerate and the antiestrogen ICI 182,780.

In the pig, appearance of endometrial glands between birth (postnatal day [PND] 0) and PND 14 involves development of estrogen receptor-alpha-positive (ER+) phenotype by, and increased DNA synthesis in, nascent glandular epithelium (GE). To determine whether ER activation is required for this process, gilts were treated daily with either vehicle, the antiestrogen ICI 182,780 (ICI), estradiol-17beta valerate (EV), or both ICI and EV. Treatments began on PND 0, before onset of adenogenesis, or on PND 7, after onset of gland proliferation. Uteri obtained on PNDs 7 and 14 (study one) or on PND 14 (study two) were weighed; uterine histology was evaluated; DNA synthesis in luminal epithelium and GE was characterized by determining 5-bromo-2'-deoxyuridine (BrdU) labeling index; and patterns of ER mRNA expression were evaluated in situ (study one). Gland genesis was inhibited by ICI, which decreased gland penetration depth by PND 14 in study one, both endometrial thickness and BrdU-labeling index in GE in study two, and increased stromal cell compaction in both studies. Uterotropic effects of EV included increased gland development and epithelial BrdU labeling and decreased stromal compaction. These effects were inhibited by coadministration of ICI. Treatments did not alter ER mRNA expression, which remained limited to stroma and GE. Data indicate that endometrial maturation and adenogenesis in the neonatal pig require expression and activation of a functional ER system.     

Effect of two-week ethanol administration on lipoprotein lipase activity and blood serum lipids in the rat

Influence of ethanol administration on adipose tissue lipoprotein lipase activity, serum lipids in the rat. Intoxication caused a decrease of lipoprotein lipase activity. In some animals a rise of serum high density lipoprotein cholesterol was observed which correlated positively with the content of cytochrome P-450 in the liver.     

Ultrasonography and endocrinology of ovarian dysfunctions induced in heifers with estradiol valerate

This study monitored the long-term follicular dynamics and changes in ovarian steroid hormones associated with an experimental model of cystic ovarian degeneration (COD) in the heifer. In the treated group (n = 7), Holstein heifers received a single injection of 500 microg of cloprostenol (prostaglandin F2a, PG) and 5 mg of estradiol valerate (EV) on either Day 17, 18 or 19 of the estrous cycle. The control group (n = 7) received only PG. Transrectal ultrasound was performed daily, beginning 8 to 10 d before injection and continuing until a return to normal cyclicity (40 to 74 d). Blood samples were taken twice daily over the same period. The EV disrupted the normal follicular development as well as the plasma progesterone and estradiol profiles of 6/7 heifers in the treated group. Two different types of responses were observed. The Type-I response (n = 2) was characterized by a premature ovulation followed by a corpus luteum (CL) which persisted for over 30 d. The Type-II response (n = 4) was characterized by anovulation followed by the emergence of a large ovarian structure which could further be subtyped. In Type- IIA (n = 2), this follicle ovulated at an exaggerated size of 19 or 24 mm (mean diameter of controls: 13.4 +/- 2.7 mm). The subsequent cavernous CL was very large at 35 and 37 mm (mean diameter of CL in controls: 23.8 +/- 2.0 mm). In Type- IIB (n = 1), the follicle present at the time of injection continued to grow and became a luteinized cyst. In Type-IIC (n = 1), several waves of follicular cysts developed and persisted for 52 d. This study suggests that EV induces a range of ovarian dysfunctions including different forms of COD. The individual differences in the stage of folliculogenesis at the time of injection of EV may be responsible for the different types of responses.     

Effects of fasting on serum lipids and lipoprotein profiles in the egg-laying hen (Gallus domesticus)

The effects of a 24-h fast on serum lipids and lipoprotein profiles in commercial laying hens were investigated. Blood was analyzed at 34 and 46 weeks of age from Single Comb White Leghorn hens that had been either fed ad libitum or had been fasted for 24 h prior to collection. At 12 weeks, birds were divided into 16 biological isolation units, with 8 replicate units assigned to each treatment group. Four birds out of 10 in each unit were tagged for bleeding. Parameters evaluated included total serum cholesterol and triglycerides, mean diameters of very low density lipoproteins (VLDLs) for the 10th, 50th, and 90th percentiles of serum total VLDL, mean total population VLDL particle diameter (MPD), and percentage serum cholesterol recovered in VLDL, low density lipoprotein (LDL), and high density lipoprotein (HDL) fractions. Fasting led to decreases in total serum cholesterol and triglycerides, and a decrease in mean serum VLDL particle diameter in the 90th population percentile. At Week 34, percentage serum cholesterol recovered from LDL was increased, whereas percentage serum cholesterol recovered from HDL was decreased due to fasting. At Week 46, MPD and percentage serum cholesterol recovered from VLDL were decreased, whereas percentage serum cholesterol recovered from HDL was increased due to fasting. It was concluded that a 24-h fast decreased serum lipids (cholesterol and triglycerides) and the size of VLDL particles in the 90th population percentile in commercial laying hens. Furthermore, bird age influenced the effects of a 24-h fast on MPD and the redistribution of serum cholesterol among VLDL, LDL, and HDL particles.     

Multiple effects of serum low-density lipoprotein on cultured human fibroblasts.

The effects of serum low-density lipoproteins (LDL) were studied in cultures of human skin fibroblasts grown in medium supplemented with human serum deficient in lipoproteins and in platelet factor. The LDL led to a temporary increase in the rate of cell replication, to increases in the cell content of protein and cholesterol, to an increase in average cell size, and to an increased secretion of glycosaminoglycans. The increases in cholesterol and protein were proportional to the increase in cell size, suggesting that the additional protein and cholesterol were of a structural, rather than a storage, nature. The increase in cell protein during the first few days of exposure to LDL was due to a decrease in the rate of protein degradation. Ultrafiltration of the serum to remove substances of molecular weight less than 30,000 did not reduce the basal rate of cell proliferation but did prevent the stimulation of proliferation by LDL; it did not alter the effect of LDL on cell protein and cholesterol, indicating that the latter responses are independent of the mitogenic action. The response of cells from diabetic donors did not differ from that of normal cells.