Association between the plasma proteome and serum ascorbic acid concentrations in humans

Vitamin C has been associated with a reduced risk of chronic diseases, but the biological pathways regulated by vitamin C are not all known. The objective was to use a proteomics approach to identify plasma proteins associated with circulating levels of ascorbic acid. Men and women (n= 1022) 20–29 years of age from the Toronto Nutrigenomics and Health Study completed a general health and lifestyle questionnaire and a 196-item food frequency questionnaire and provided a fasting blood sample. Circulating ascorbic acid was analyzed by high-performance liquid chromatography, and a mass-spectrometry-based multiple reaction monitoring method was used to measure 54 proteins abundant in plasma that are involved in numerous physiologic pathways. Mean protein concentrations were compared across tertiles of serum ascorbic acid using analysis of covariance adjusted for sex, ethnocultural group, season of blood draw, hormonal contraceptive use among women, waist circumference and tertiles of plasma α-tocopherol. A Bonferroni significance level of P<.0009 was applied, and analyses were adjusted for multiple comparisons using the Tukey–Kramer procedure. Levels of complement C9, ceruloplasmin, alpha-1-anti-trypsin, angiotensinogen, complement C3, vitamin D binding protein and plasminogen were inversely associated with levels of ascorbic acid. The inverse association between ascorbic acid and vitamin D binding protein was highest in those with higher levels of serum 25-hydroxyvitamin D. In conclusion, several plasma proteins from various physiologic pathways are significantly associated with circulating levels of ascorbic acid. These findings suggest that vitamin C may have novel physiological effects.     

Ciprofloxacin concentrations in serum, bone and bone marrow of rabbits

Ciprofloxacin concentrations were determined in serum, bone and bone marrow of rabbits. Four experimental groups of animals were examined: group A (n = 6) received a dosage of 60 mg/kg/day intramuscularly for 4 weeks, groups B (n = 6), C (n = 15) and D (n = 15) received dosages of 120 mg/kg/day subcutaneously for 2 days, 2 weeks, and 4 weeks, respectively. In the kinetic portion of the study, peak serum concentrations of ciprofloxacin measured at the 15 min sampling time were: 2.61 +/- 0.27 micrograms/ml in the 60 mg/kg/day group (group A) and 3.24 +/- 0.78 micrograms/ml in the 120 mg/kg/day group (group B). At necropsy, rabbits in group A had mean ciprofloxacin concentrations of 3.60 +/- 2.27 micrograms/ml in serum, 2.24 +/- 1.19 micrograms/g in marrow and 1.19 +/- 0.44 micrograms/g in bone. Rabbits in group B achieved mean levels of 4.02 +/- 1.23 micrograms/ml in serum, 2.48 +/- 0.79 micrograms/g in marrow, and 1.35 +/- 0.40 micrograms/g in bone. Rabbits in group C achieved mean levels of 5.65 +/- 2.16 micrograms/ml in serum, 3.74 +/- 1.33 micrograms/g in marrow and 1.92 +/- 0.94 micrograms/g in bone. Rabbits in group D achieved mean levels of 7.24 +/- 2.50 micrograms/ml in serum, 4.48 +/- 1.68 micrograms/g in marrow, and 1.93 +/- 0.54 micrograms/g in bone. Differences between mean values for the four experimental groups were not statistically significant.     

Abrupt modifications of phospholipid bilayer properties at critical cholesterol concentrations.

The fluorescence generalized polarization (GP) of 2-dimethylamino-6-lauroylnaphthalene (Laurdan) reveals different effects of cholesterol on the phase behavior of phospholipid bilayers. Phospholipid vesicles composed of gel, liquid-crystalline, and coexisting domains of the two phases have been studied at temperatures from 1 to 65 degrees C, without cholesterol and with cholesterol concentrations of 3-50 mol %. Laurdan GP measurements show the general effect of cholesterol of increasing the molecular dynamics of the gel and of decreasing the molecular dynamics of the liquid-crystalline phase. In the liquid-crystalline phase, the increased order yields Laurdan GP values close to those obtained in the gel phase. At cholesterol concentrations > 15 mol % a phase transition cannot be detected. Using the wavelength dependence of the excitation and emission GP spectra we determine that differences between the two phospholipid phases cannot be detected. In particular, in vesicles composed of coexisting gel and liquid-crystalline phases the GP wavelength dependence characteristic of coexisting domains cannot be observed at cholesterol concentrations > or = 15 mol %. Cholesterol causes the decrease in both the polarity and the dipolar relaxation effects on the neighborhood of the fluorescent naphthalene moiety of Laurdan. Probably because of a cholesterol-induced increase in the bilayer packing, these effects do not occur continuously with the increase of cholesterol concentration in the bilayer. Cholesterol concentrations inducing higher Laurdan GP values have been determined at about 5, 10, 15, 30, and 45 mol % with respect to phospholipids. We propose that the formation of ordered molecular microdomains at critical cholesterol concentrations can explain the occurrence of the observed discontinuities.     

Circulating lipoprotein cholesterol concentrations in the summer-active ground squirrel (Spermophilus lateralis): a comparison with those in humans and rabbits.

1. The concentrations of total cholesterol (free cholesterol plus cholesteryl ester) in the sera and in two lipoprotein fractions of golden-mantled ground squirrels (Spermophilus lateralis) were measured and compared to those found in humans and New Zealand White rabbits (Oryctolagus cuniculus). 2. Squirrels showed significantly higher concentrations of total serum cholesterol (TSC; P less than 0.0005), high density lipoprotein cholesterol (HDL-C; P less than 0.0005), and very low density plus low density lipoprotein cholesterol (VLDL + LDL-C; P less than 0.0005) than those in rabbits. 3. Squirrels had significantly higher TSC (P less than 0.0005) and HDL-C (P less than 0.0005) concentrations than did humans. 4. Squirrels additionally exhibited significantly lower TSC/HDL-C ratios than did rabbits (P less than 0.005) or humans (P less than 0.0005). 5. The significant differences in lipoprotein metabolism observed in this study between the active hibernator and non-hibernators, may reflect the marked biochemical and physiological adjustments hibernating species make throughout their circannual cycle.     

Factors influencing the serum levels of cholesterol and beta-lipoproteins in starving rabbits]

The influence of starvation on the lipid metabolism was studied on male rabbits under usual conditions and in the presence of pyroxidine deficiency (4-deoxypyridoxine administration) and of thiamine (oxythiamine administration), and also in administration of neurotropic preparations (phenamine, seduxen). Starvation for 7 to 10 days led to increase of cholesterol and beta-lipoproteins level in the serum. Pyridoxine deficiency and phenamine administration caused a greater increase of cholesterol and especially or beta-lipoproteins. On the other hand, thiamine deficiency and seduxen administration limited an increase of cholesterol and beta-lipoproteins during hungry stress. Administration of aerovit for prophylactic purpose promoted a decrease of the metabolic shifts. The amount of cholesterol increased in the liver of hungry animals, especially after the phenamine administration and in the presence of pyridoxine deficiency; aerovit administration prevented increased cholesterol accumulation in the liver. The differences in the cholesterol level in the serum and and the liver can be explained by the changes of its biosynthesis during hungry stress.     

Spontaneous transfer between phospholipid bilayers of dehydroergosterol, a fluorescent cholesterol analog

The spontaneous interbilayer transfer of dehydroergosterol, a fluorescent cholesterol analog, was examined using small unilamellar phospholipid vesicles. The kinetic data were best fit by an equation of the form Aexp (-kt) + B. Qualitatively, the general trend of the half-time for transfer and the base values (B) obtained for dehydroergosterol resemble the corresponding values obtained in the earlier studies of cholesterol transfer. However, quantitative differences, which reflect the molecular structure of the sterol, were observed. Acrylamide quenching performed on the donor vesicles at different stages of the transfer indicated that a time-dependent organization of DHE within the vesicles occurs.     

Relationships of liver weight, cholesterol, albumin and alpha2-macroglobulin concentrations with ovarian function in swine

In two genetic swine models selected for diversity in ovulation rates (White composite controls and ovulation rate selection line, n = 131; 1/2 White composite: 1/2 Meishan crossbreds, n = 387), a positive relationship was established with liver weight and ovulation rate (P < 0.01). Serum changes of cholesterol, albumin and alpha2-macroglobulin were monitored during various stages of the luteal phase and follicular phase (days 17 and 19 of the estrous cycle; 1/2 White composite: 1/2 Meishan gilts). Serum cholesterol concentrations increased with liver weights (r = 0.19; P < 0.01) and corpora lutea numbers (r = 0.14; P < 0.01). Albumin concentrations were negatively correlated with corpora luteal numbers (r = -0.3; P < 0.01) but had no relationship with liver weight. Serum concentrations of alpha2-macroglobulin were not related to liver weight or corpora lutea numbers. Circulating concentrations of cholesterol and alpha2-macroglobulin increased with day of the estrous cycle (P < 0.01). Testosterone concentrations were inversely related to circulating cholesterol concentrations during the estrous cycle, but testosterone concentrations on day 17 or 19 of the cycle were unrelated to corpora lutea numbers. Concentrations of estrone on day 17 or 19 (as an index of follicles destined to ovulate) were also not related to numbers of corpora lutea. Many interactions between liver and ovarian function involving metabolic and endocrine systems are plausible, but defined mechanisms resulting in coordinate increases in liver weight and ovulation rates are presently unelucidated.     

Growth in utero and serum cholesterol concentrations in adult life.

OBJECTIVE--To see whether reduced rates of fetal growth are related to raised serum cholesterol concentrations in adult life. DESIGN--Follow up study of men and women whose size at birth had been recorded. SETTING--Jessop and Northern General Hospitals, Sheffield. SUBJECTS--219 men and women born in the Jessop Hospital during 1939-40. MAIN OUTCOME MEASURES--Serum concentrations of total cholesterol, low density lipoprotein cholesterol, and apolipoprotein B. RESULTS--Men and women who had had a small abdominal circumference at birth had raised serum concentrations of total and low density lipoprotein cholesterol and apolipoprotein B. This was independent of the duration of gestation. Serum concentrations of total cholesterol fell by 0.25 mmol/l (95% confidence interval 0.09 to 0.42) with each 1 in (2.54 cm) increase in abdominal circumference. The corresponding figure for serum low density lipoprotein cholesterol was 0.26 mmol/l (0.11 to 0.42) and for serum apolipoprotein B 0.04 g/l (0.02 to 0.07). Small head and chest circumferences at birth and short length were each associated with raised serum low density lipoprotein cholesterol concentrations but the trends disappeared in a simultaneous regression with abdominal circumference at birth. The association between abdominal circumference at birth and low density lipoprotein cholesterol concentration was independent of social class, current body weight, cigarette smoking, and alcohol consumption. CONCLUSION--Raised serum cholesterol concentrations in adult life are associated with impaired growth during late gestation, when fetal undernutrition has a disproportionate effect on liver growth. Impaired liver growth may permanently alter low density lipoprotein cholesterol metabolism.     

Effect of polyenoic phospholipid therapy on lecithin cholesterol acyltransferase activity in the human serum

The effect of polyenoic phospholipids on the concentration of serum lipids and the activity of lecithin cholesterol acyltransferase (LCAT, E.C. 2.3.1.43) was investigated in 18 patients with chronic glomerulonephritis accompanied by hyperlipaemia and reduced rate of cholesterol esterification in the plasma. The effects of therapy were evaluated immediately after a 2-month period of treatment and again after a 3-month drug free interval following termination of the therapy. An immediate effect of the treatment was reflected in a significant increase in the fractional esterification rate (FER % .h-1) and a marked reduction of the concentration of triglycerides (TG). Discontinuation of the drug resulted in the return of TG and FER values to the initial levels and in a rise of total (TCH) and unesterified cholesterol (UCH), HDL-cholesterol (HDL-TCH) and the molar esterification rate (MER mumol.1-1.h-1). The activity of LCAT estimated by radioassay in common and endogenous substrates varied in parallel.     

Concentrations of serum cortisol, progesterone, estradiol-17 beta, cholesterol and cholesterol ester in the doe during the reproductive stadium, in the fetal serum, in the amniotic fluid and in the milk of rabbits, as well as correlations between these parameters

1. Serum progesterone, estradiol-17 beta and cortisol, as well as cholesterol and cholesterol ester concentrations in pregnant and lactating rabbits (New Zealand white hybrids, n = 9), were measured. These parameters were also studied in the amniotic fluid, the milk and the fetal serum (28-day old fetuses). 2. Serum progesterone and estradiol-17 beta were significantly enhanced during gestation, while the content of cortisol showed a marked elevation at the end of pregnancy. The concentrations of these hormones decreased before parturition. 3. Serum cholesterol and cholesterol ester concentrations markedly decreased in the second half of gestation (74 and 76%, respectively) and elevated after parturition and in the first week of lactation.