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At least 307 records · Page 17Linked to original sources

PubMed2003

C-reactive protein concentration and concentrations of blood vitamins, carotenoids, and selenium among United States adults.

OBJECTIVE: To examine the relationships between circulating concentrations of C-reactive protein and concentrations of retinol, retinyl esters, vitamin C, vitamin E, carotenoids, and selenium. DESIGN: Cross-sectional study using National Health and Nutrition Examination Survey III (1988-1994) data. SETTING: United States population. SUBJECTS: Up to 14 519 US noninstitutionalized civilian men and women aged > or=20 y. RESULTS: C-reactive protein concentration (dichotomized at the sex-specific 85th percentile) was inversely and significantly associated with concentrations of retinol, retinyl esters, vitamin C, alpha-carotene, beta-carotene, cryptoxanthin, lutein/zeaxanthin, lycopene, and selenium after adjustment for age, sex, race or ethnicity, education, cotinine concentration, body mass index, leisure-time physical activity, and aspirin use. CONCLUSIONS: These results suggest that the inflammatory process, through the production of reactive oxygen species, may deplete stores of antioxidants. Whether increased consumption of foods rich in antioxidants or supplementation with antioxidants can provide health benefits to people characterized by elevated C-reactive protein concentrations may be worthy of further study.

Adult↗

PubMed1997

Marked increases in concentrations of apolipoprotein in the cerebrospinal fluid of poliovirus-infected macaques: relations between apolipoprotein concentrations and severity of brain injury.

Apolipoproteins in cerebrospinal fluid (CSF) might have important functional roles in the pathophysiology of brain and lipid metabolism in the vascular component. The present study examined apolipoprotein A-I (apo-A-I) and apolipoprotein E (apo-E) levels in CSF and serum from poliovirus-infected macaques. Poliovirus-infected macaques developed motor deficits and were classified into three groups: (1) muscle weakness in one or both legs; (2) partial paralysis in one or both legs; (3) complete paralysis in one or both legs. No motor deficits were evident in the control or sham-treated macaques. Apo-A-I concentrations in CSF were markedly elevated in poliovirus-infected macaques with weakness, partial or complete paralysis, in comparison with either control or sham-treated animals, and were proportional to the severity of motor impairment. Apo-E concentrations in CSF were also significantly elevated in poliovirus-infected macaques with complete paralysis. The magnitude of increase in CSF apo-A-I or apo-E concentrations was also closely associated with the degree of histologic neurological damage and inflammation (lesion scores). However, no changes in serum apo-A-I and apo-E concentrations were observed in the poliovirus-infected macaques compared with control macaques. Furthermore there were no significant correlations apo-A-I or apo-E concentrations between serum and CSF. We hypothesize that the elevation of apo-A-I and apo-E concentrations after poliovirus infection is caused by immune stimulation within the central nervous system (CNS). Measures of CSF apo-A-I and apo-E levels might serve as a useful marker for the severity and/or the range of CNS injury.

Animals↗

PubMed1996

Low concentrations of ouabain increase cytosolic free calcium concentration in rat vascular smooth muscle cells.

1. Low ouabain concentrations in the nanomolar range significantly increased cytosolic free calcium concentration. 2. The ouabain-induced cytosolic free calcium concentration increase was due to transplasmamembrane calcium influx, which could be prevented in the absence of extracellular calcium or by addition of the calcium channel blocker nifedipine. 3. The amount of stored cellular Ca2+, as determined by the thapsigargin-induced cytosolic free calcium concentration increase, was also enhanced by 1 nmol/l ouabain. 4. It is concluded that low ouabain concentrations affect intracellular cytosolic free calcium concentration homoeostasis.

Animals↗

PubMed2000

Preparation and storage characteristics of white cell-reduced high-concentration platelet concentrates collected by anapheresis system for transfusions in utero.

BACKGROUND: Important concerns with regard to in utero platelet transfusions are avoidance of volume overload and the immunomodulatory effects of residual white cells (WBCs). This study evaluated a modification of a leukocyte-reduction system (LRS, Spectra, COBE BCT) for apheresis, which collects high-concentration WBC-reduced platelets (HCPs) for in utero transfusion. STUDY DESIGN AND METHODS: The LRS procedure was modified by running the platelet collection pump at specified low flow rates (Q(col)) for the first part of the procedure, collecting HCPs by gently purging them from the LRS chamber into a designated collection bag and then restoring the original LRS procedure settings to collect a second standard apheresis platelet concentrate (PC). Two centers carried out 32 procedures. Platelet yield, residual WBCs, and in vitro platelet function studies were evaluated. RESULTS: Platelet concentrations in 60 mL of HCPs were predictable according to Q(col) (r(2) = 0.735). HCP yields varied from 0.9 to 3.2 x 10(11), depending on the desired final platelet concentrations in 60 mL, with an overall average of 1. 92 x 10(11) (n = 32). Apheresis PCs had a mean platelet yield of 2.9 x 10(11) (1.3-4.4 x 10(11), n = 20) and 3.9 x 10(11) (2.2-5.8 x 10(11), n = 12) at concentrations of 1.3 x 10(12) per L for single-needle and dual- needle procedures, respectively. Median WBC counts were 5.6 x 10(3) for HCPs and 2.0 x 10(4) for apheresis PCs, with >99 percent expected to be less than 1 x 10(6). HCP in vitro characteristics were equivalent to those of apheresis PCs at 24 hours after collection. In vitro performance declined over storage as a function of HCP yield. HCP pH at 22(o)C was maintained at a level of >6.2 for more than 3 days for yields >1.6 x 10(11), less than 2 days for yields 1.6 to 2.2 x 10(11), and less than 24 hours for yields >2.2 x 10(11). HCPs showed good in vitro characteristics and could be stored for 1 to 3 days, depending on the total number of platelets collected. CONCLUSION: A standard apheresis PC and an HCP requiring no secondary processing can be collected with the Spectra LRS. The platelet concentration may be determined by clinical need. HCPs meet the requirements for components that are transfused in utero.

Blood Platelets↗

PubMed1977

The effect of short term physiological elevations of plasma glucagon concentration on plasma triglyceride concentration in normal and diabetic man.

To explore the effect of physiological elevations of glucagon on plasma triglyceride concentration, glucagon was infused for thirty minutes at 3.0 ng/kg/min into both normal and insulin dependent diabetic subjects. The effects of this hormonal infusion on plasma triglyceride, free fatty acids, glucose, and insulin were compared to a control saline infusion study. A differential effect of glucagon on plasma triglyceride concentration between normal and diabetic subjects was observed. In normal subjects, glucagon infusion was accompanied by a concomitant increase in endogenous insulin secretion and free fatty acid levels, and no observable effect on circulating plasma triglyceride concentration. In contrast, in diabetic subjects, no change in insulin or free fatty acid concentration occurred during glucagon infusion and circulating plasma triglyceride concentration declined after twenty minutes of hormone infusion. These results suggest that plasma triglyceride concentration may be modulated, at least in part, by alterations in circulating plasma glucagon in concert with insulin secretion and free fatty acid availability in man.

Adult↗

PubMed1999

Higher total homocysteine concentrations and lower folate concentrations in premenopausal black women than in premenopausal white women.

BACKGROUND: Premenopausal black women have a greater rate of coronary artery disease (CAD) than do premenopausal white women. Plasma total homocysteine concentrations, a risk factor for CAD, have not been reported in premenopausal black women. OBJECTIVE: The purpose of this study was to compare plasma total homocysteine, folate, and vitamin B-12 concentrations in premenopausal black and white women. DESIGN: Eighty-nine black and 90 white, healthy, premenopausal women living in Portland, OR, were recruited. Dietary histories were obtained by using the Diet Habit Survey, a 40-item eating-behavior questionnaire. Plasma concentrations of total homocysteine, folate, and vitamin B-12 were measured. RESULTS: Black women had higher plasma total homocysteine (8.32 compared with 7.60 micromol/L;P = 0. 013), lower plasma folate (6.62 compared with 9.88 nmol/L;P < 0. 0001), and higher vitamin B-12 (355 compared with 283 pmol/L;P < 0. 001) concentrations than white women. White women had a greater rate of daily multivitamin supplement use (42.4% compared with 24.7%;P = 0.019) and ate more ready-to-eat cereal than did black women. After adjustment for multivitamin use and intake of ready-to-eat cereal, plasma total homocysteine concentrations did not differ significantly, but plasma folate remained significantly lower in the black women. None of the black women but 12.3% of the white women (P = 0.013) were homozygous for the cytosine to thymidine mutation at nucleotide 677 in the methylenetetrahydrofolate reductase gene. CONCLUSIONS: Black women had higher plasma total homocysteine and lower plasma folate concentrations than white women, largely because of lifestyle factors, which may contribute to the greater rate of CAD in premenopausal black than in white women.

Adolescent↗

PubMed2002

Fatty acid saturation of the diet and plasma lipid concentrations, lipoprotein particle concentrations, and cholesterol efflux capacity.

BACKGROUND: The fatty acid content and saturation degree of the diet can modulate HDL composition and cholesterol efflux. OBJECTIVE: We studied the modifications in plasma lipoprotein particles and serum capacity to stimulate cholesterol efflux induced by different fatty acids. DESIGN: Seventeen women and 24 men followed in the same sequence 4 diets containing 35% of total energy as fat. The saturated fat diet contained 17% palm oil; the monounsaturated fat diet, 20.9% olive oil; the n-6 polyunsaturated fat diet, 12.5% sunflower oil; and the n-3 polyunsaturated fat diet, sunflower oil supplemented with 4-4.5 g fish oil/d. Each phase lasted 4-5 wk. RESULTS: In both sexes, apolipoprotein (apo) A-I concentrations were significantly lower with unsaturated fat diets than with the saturated fat diet, but concentrations of lipoproteins containing only apo A-I (Lp A-I) were lower only in the men. Concentrations of lipoproteins containing both apo A-I and apo A-II (Lp A-I:A-II) were lower with both polyunsaturated fat diets in the women but significantly higher in the men. Lp E concentrations were significantly higher with the 2 polyunsaturated fat diets. Lp E non-B particle concentrations were not modified in the men but were significantly higher in the women in both polyunsaturated fat phases. Lp C-III concentrations were higher with the saturated fat diet only in the men. The serum samples taken after the n-3 polyunsaturated fat phase were the most efficient for extracting cellular cholesterol in both sexes. CONCLUSIONS: The monounsaturated and polyunsaturated fat diets were healthier, producing a better lipid profile. The n-3 polyunsaturated fat diet increased the capacity of serum to promote the efflux of cholesterol from cells in culture.

Apolipoproteins↗

PubMed2002

Macular pigment density in relation to serum and adipose tissue concentrations of lutein and serum concentrations of zeaxanthin.

BACKGROUND: Macular pigment (MP), concentrated in the central area of the retina, contains the carotenoids lutein and zeaxanthin. A low MP density could be a risk factor for age-related macular degeneration. Little information is available regarding MP density in relation to serum lutein and zeaxanthin and adipose lutein concentrations in a general population. OBJECTIVE: The objective was to investigate the associations between MP density and serum lutein, serum zeaxanthin, and adipose lutein, taking into account potential confounders in a population. DESIGN: Volunteers (n = 376) aged 18-75 y were recruited. In a cross-sectional design, serum (n = 376) and adipose tissue (n = 187) were analyzed for carotenoids, and MP density was measured by spectral fundus reflectance. RESULTS: Mean MP density in the total study group was 0.33 +/- 0.15. MP density was 13% higher in men than in women (P < 0.05). Serum and blood concentrations of alpha-tocopherol, vitamin C, and all carotenoids except lycopene were significantly higher in women. Adipose lutein concentrations were also significantly higher in women than in men. Regression models showed a positive significant association between MP density and serum lutein, serum zeaxanthin, and adipose lutein concentrations in men after adjustment for age, but no relation in women. In men, serum lutein remained significantly associated with MP density after adjustment for age, total cholesterol, body mass index, and smoking. CONCLUSION: The associations between MP density and serum lutein, serum zeaxanthin, and adipose lutein concentrations are stronger in men than in women.

Adipose Tissue↗

PubMed1991

Changes in blood pressure, plasma triglyceride and aldosterone concentration, and red cell cation concentration in patients with hyperinsulinemia.

Blood pressure, plasma concentration of triglyceride, aldosterone, renin activity (PRA), and atrial naturietic peptide (ANP), and red blood cell, urine, and plasma sodium and potassium concentration were determined in 24 healthy individuals divided into two groups defined as being either hyperinsulinemic or normoinsulinemic. The results demonstrated that the hyperinsulinemic group had significantly higher values for both systolic (P less than .01) and diastolic (P less than .05) blood pressure. In addition, plasma concentrations of triglyceride (P less than .02), aldosterone (P less than .05) and potassium (P less than .05) were higher in hyperinsulinemic individuals as compared to those who were normoinsulinemic. Furthermore, red cell potassium was lower (P less than .01) and red cell sodium higher (P less than .01) in the hyperinsulinemic group. Finally, the magnitude of hyperinsulinemia correlated directly with systolic (r = 0.50, P less than .01) and diastolic (r = 0.44, P less than .05) blood pressure, concentration of plasma triglyceride (r = 0.55, P less than .01) and aldosterone (r = 0.46, p less than .05), and erythrocyte sodium concentration (r = 0.57, p less than .01). In contrast, plasma insulin response was negatively correlated with erythrocyte potassium concentration (r = 0.40, P less than 0.05). These observations provide further support for the view that hyperinsulinemia, presumably secondary to resistance to insulin-stimulated glucose uptake, is associated with a cluster of variables that may play important roles in the etiology and clinical course of hypertension.

Aldosterone↗

PubMed1994

Relationship between plasma concentrations of 3'-deoxy-3'-fluorothymidine (alovudine) and antiretroviral activity in two concentration-controlled trials.

Two concentration-controlled trials (CCTs) defined the relationship between plasma concentrations of 3'-deoxy-3'-fluorothymidine (alovudine) and changes in surrogate markers of antiretroviral activity. In an initial open-label CCT involving 14 subjects infected with human immunodeficiency virus (HIV), unacceptable hematologic toxicity occurred when the area under the concentration-time curve during a 12-h dosing interval (AUC12) was > or = 300 ng*h/mL. Consequently, 46 subjects were assigned to AUC12s of 50, 100, or 200 ng*h/mL for up to 16 weeks in a prospective, randomized, double-blind CCT. Alovudine caused a concentration-dependent reduction in p24 antigen and peripheral blood mononuclear cell HIV titers within 4 weeks of start of treatment. The AUC12 producing a 50% reduction in p24 (108 ng*h/mL) had a trough concentration identical to the reported IC50 of alovudine in HIV-infected H9 cells. It may be possible to predict the antiretroviral activity of certain nucleoside analogues as a function of plasma drug concentration.

Adult↗

PubMed1984

Bioavailability of zinc to rats from defatted soy flour, acid-precipitated soy concentrate and neutralized soy concentrate as determined by intrinsic and extrinsic labeling techniques.

The bioavailability of 65Zn from intrinsically and extrinsically labeled soy flour, acid-precipitated soy concentrate and neutralized soy concentrate was evaluated in rats. Weanling rats were fed marginally zinc-deficient diets, providing 8 ppm zinc from one of these three soy products, for 7 days. The rats then received a radioactively labeled test meal, identical in composition to the previous diet except that the soy product was either intrinsically or extrinsically labeled with 65Zn. After the test meal the rats were again fed diets the same as those consumed prior to the test meal. Whole-body retention of 65Zn at 24 hours and 12 days as well as 65Zn retained in tibias of rats given meals containing neutralized concentrate-based meals was significantly lower than for rats given meals containing the soy flour or acid-precipitated concentrate. In addition, retention of 65Zn from the extrinsically labeled acid-precipitated concentrate-based meal was significantly higher than from the same product intrinsically labeled. These findings confirm the results of previous feeding studies from which it was suggested that neutralization of soy protein concentrates reduces zinc bioavailability to the rat. In addition, the results are taken to suggest that experimental conditions may influence the validity of the extrinsic labeling technique for zinc.

Animals↗

PubMed1994

Serum luteinizing hormone pulsatility and intratesticular testosterone and oestradiol concentrations in idiopathic infertile men with high and normal follicle stimulating hormone serum concentrations.

The purpose of the study was to evaluate pulsatile luteinizing hormone (LH) release and intratesticular concentrations of testosterone and oestradiol in infertile men, to determine if alterations in gonadotrophin secretion are associated with changes in the testicular concentrations of steroids. Patients with idiopathic oligo/azoospermia were divided into a high follicle stimulating hormone (FSH) group (n = 5) and a normal FSH group (n = 6). Blood samples were taken every 15 min for 6 h to determine LH, FSH, testosterone, oestradiol, sex hormone binding globulin, bioactive LH and bioavailable testosterone. The patients underwent a bilateral testicular biopsy for histological assessment and to determine testosterone and oestradiol concentrations. Serum measurements were compared with those of seven fertile men. The high FSH group had a higher concentration of serum LH and oestradiol than normal men (P < 0.01) and showed a lower frequency of LH pulses than the normal FSH group and control men (P < 0.01). Intratesticular oestradiol was higher in the high FSH group (P < 0.001), with a lower testosterone/oestradiol ratio (P < 0.01). Patients showed a negative correlation between the serum testosterone/LH ratio and FSH (r = -0.75; P < 0.01) and a positive correlation between the testicular oestradiol concentration and serum FSH (r = 0.86; P < 0.01). The histopathological examination only showed a smaller tube diameter in the high FSH group (P < 0.05). These data seem to indicate that a higher intratesticular concentration of oestradiol with a lower testosterone/oestradiol ratio in the high FSH group could have a deleterious effect on spermatogenesis.

Adult↗

PubMed1998

Minimum alveolar anesthetic concentrations for airway occlusion in cats: a new concept of minimum alveolar anesthetic concentration-airway occlusion response.

UNLABELLED: Minimum alveolar anesthetic concentration (MAC) is defined as an end-tidal concentration of inhaled anesthetic required to prevent purposeful movement (positive motor response) in 50% of subjects to somatic noxious stimuli. Although MAC for visceral noxious stimuli has not been well investigated, airway occlusion can be a noxious respiratory stimulus that can induce a visceral sensation of choking. In this study, MAC for airway occlusion (MAC-AOR) was determined during halothane, isoflurane, and sevoflurane anesthesia and compared with the MAC values for somatic noxious stimuli such as toe pinch (MAC-pinch) or tetanic stimulus (MAC-tetanus) in cats. Thirty-four adult cats were used. In 24 cats, the motor responses to three different stimuli (toe pinch, tetanic stimulus, and airway occlusion for 6 min) were observed during inhaled anesthesia and rated as positive or negative. The concentration of an inhaled anesthetic was changed in steps of 0.1%-0.2 vol% until the bracketing procedure (i.e., the highest concentration of inhaled anesthetic permitting a positive motor response and the lowest concentration preventing the response were determined) was completed. In 10 cats, the effect of anesthetic duration on MAC-AOR was also investigated. Each mean MAC (MAC-pinch, MAC-AOR, and MAC-tetanus, respectively) was as follows: halothane 0.99, 1.13, and 1.46; isoflurane 1.50, 1.65, and 2.22; and sevoflurane 3.07, 3.38, and 3.95. The first and last MAC-AOR values determined during 6-h halothane anesthesia were 1.10 and 1.11, respectively. In conclusion, airway occlusion can be a noxious stimulus and can induce an all-or-none type of motor response, depending on the depth of inhalational anesthesia in cats. This phenomenon can permit the introduction a new concept of MAC-AOR. IMPLICATIONS: Airway occlusion can be a noxious visceral stimulus and induce all-or-none type of motor response in cats, depending on the depth of inhalational anesthesia. This permits the introduction of a new concept of minimum alveolar anesthetic concentration airway occlusion response.

Airway Obstruction↗

PubMed1996

A proposed model to monitor heparin therapy using the concentrated thrombin time which allows standardisation of reagents and improved estimation of heparin concentrations.

The concentrated thrombin time (CTT), a thrombin time performed with a high concentration of thrombin, was evaluated as an alternative to the activated partial thromboplastin time (APTT) for monitoring of heparin therapy. Forty-nine plasmas from patients receiving unfractionated heparin therapy were tested. It was first demonstrated that CTTs using three commercial reagents could be standardised against CTTs performed with a reference reagent, MRC reagent 66/305. For comparison, APTTs were performed on the plasmas. As a benchmark of the degree of heparinisation, the heparin concentration of the plasmas was determined by chromogenic anti-IIa heparin assays, therapeutic range being 0.2-0.4 units/ml. The optimal relationships of the CTTs and APTT with the heparin concentration were established. These were used to predict the heparin concentrations of the plasmas from the results of the APTT, CTT performed with the reference reagent, and transformed CTT performed with each of the three commercial reagents. In predicting the assayed plasma heparin concentrations, the accuracy of the APTT was only 53%, while the CTT was from 78 to 82%. The CTT can be standardised and, subject to results of clinical trials, could provide an improved method of monitoring heparin therapy.

Afibrinogenemia↗

PubMed1989

Correlation of lung dose with Rn concentration, potential alpha-energy concentration and daughter surface deposition: a Monte Carlo analysis.

In the evaluation of lung cancer risk from Rn daughters in the home environment, measurements of Rn concentration or potential alpha-energy concentration (PAEC) have served as proxies for actual radiation dose to the lungs. This paper uses a single-compartment room model, model parameters from a number of recent studies, and Monte Carlo analysis to explore the relative value of Rn concentration, PAEC, and room surface deposition, or plate-out, as estimators of lung dose. Results indicate that Rn concentration and PAEC are fairly good estimators, explaining roughly 50-70% of the variation in dose for the conditions studied, over the range of Rn concentrations considered (74-555 Bq m 3). The relative advantage of one measure over the other depends upon the variability in a number of factors across the houses being evaluated. Room surface activity deposition was not found to be superior to the traditional measures of Rn concentration and PAEC. Significant room for improvement remains in the development of simple home monitors providing an improved estimation of lung dose.

Air Pollutants↗

PubMed1998

Comparison of total and free phenytoin serum concentrations measured by high-performance liquid chromatography and standard TDx assay: implications for the prediction of free phenytoin serum concentrations.

The free fraction of phenytoin (PHT) in serum increases considerably in combination with valproic acid (VPA), depending on the VPA concentration. Equations to predict the free PHT concentration (PHTf) from the total PHT concentration (PHTt) and from the VPA concentration were developed by Haidukewych and colleagues. (equation 1: PHTf = 0.095 x PHTt + 0.001 x VPA x PHTt) and May and colleagues (equation 2: PHTf = 0.0792 x PHTt + 0.000636 x VPA x PHTt]; in both equations, PHTf, PHTt, and VPA are given in microg/ml. Obviously, the equations give different predictions. The aim of this study was to investigate whether different methods for the determination of PHTt and PHTf were responsible for the differences; equation 1 was calculated from standard TDx measurements and equation 2 from high-performance liquid chromatography (HPLC) values. A total of 52 samples from patients with VPA (n=26) or without VPA (n=26) were analyzed using HPLC and TDx. The concentrations measured by HPLC and TDx were highly correlated but TDx yields significantly higher PHTt (Y = 0.98 x X + 2.46; X = HPLC, Y = TDx, r2 = 0.957) and, in particular, higher PHTf concentrations (Y = 1.03 x X + 0.30; X = HPLC, Y = TDx, r2 = 0.919), compared with our HPLC method. The accuracy of the predictive equations depends on the method used for the determination of PHTt and PHTf. The best predictions of PHTf were obtained if equation 2 and HPLC measurements were used. However, the differences in the predicted PHTf could only partly be explained by the different methods of determination.

Chromatography, High Pressure Liquid↗

PubMed1997

The Xenopus Brachyury promoter is activated by FGF and low concentrations of activin and suppressed by high concentrations of activin and by paired-type homeodomain proteins.

The mesoderm of Xenopus laevis arises through an inductive interaction in which signals from the vegetal hemisphere of the embryo act on overlying equatorial cells. One candidate for an endogenous mesoderm-inducing factor is activin, a member of the TGFbeta superfamily. Activin is of particular interest because it induces different mesodermal cell types in a concentration-dependent manner, suggesting that it acts as a morphogen. These concentration-dependent effects are exemplified by the response of Xbra, expression of which is induced in ectodermal tissue by low concentrations of activin but not by high concentrations. Xbra therefore offers an excellent paradigm for studying the way in which a morphogen gradient is interpreted in vertebrate embryos. In this paper we examine the trancriptional regulation of Xbra2, a pseudoallele of Xbra that shows an identical response to activin. Our results indicate that 381 bp 5' of the Xbra2 transcription start site are sufficient to confer responsiveness both to FGF and, in a concentration-dependent manner, to activin. We present evidence that the suppression of Xbra expression at high concentrations of activin is mediated by paired-type homeobox genes such as goosecoid, Mix.1, and Xotx2.

3T3 Cells↗

PubMed1993

Bile concentration promotes nucleation of cholesterol monohydrate crystals by increasing the cholesterol concentration in the vesicles.

Cholesterol in bile is solubilized in mixed micelles and cholesterol-phospholipid vesicles. Biliary cholesterol supersaturation and increased concentration of bile in the gallbladder promotes nucleation of cholesterol monohydrate crystals and gallstone formation, possibly by creating unstable vesicles with a high cholesterol/phospholipid ratio. In the present study super-saturated and unsaturated biles (cholesterol saturation index (CSI) 1.4 and 0.8 respectively) were prepared with concentrations typical of gallbladder and more dilute hepatic bile (total lipid concentration (TLCo) 10 and 2.5 g dl-1 respectively). The distribution of cholesterol between vesicles and micelles, and vesicular cholesterol/phospholipid ratio were studied using ultracentrifugation and gel-permeation chromatography. The nucleation time of cholesterol crystals was determined in whole model bile, and in the vesicular and micellar peak fractions. Increased CSI and bile dilution led to an increased proportion of cholesterol solubilized in vesicles. The concentration of bile did not influence vesicular cholesterol/phospholipid ratio. The vesicular cholesterol/phospholipid ratio found in gel-permeation chromatography experiments was similar at high and low CSI, whereas the ratio was significantly higher in supersaturated than in unsaturated biles in ultracentrifugation studies. Nucleation of cholesterol crystals from whole model bile was more rapid at the higher bile concentration and higher cholesterol saturation. Nucleation time in whole model bile correlated significantly with nucleation time in the corresponding vesicular peak fraction obtained by gel-permeation chromatography (r = 0.58: P < 0.01) and with the cholesterol concentration in this vesicular peak (r = -0.77; P < 0.002) but not with vesicular peak cholesterol/phospholipid ratio.(ABSTRACT TRUNCATED AT 250 WORDS)

Bile↗