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Comparison of heroin and cocaine concentrations in saliva with concentrations in blood and plasma.

Saliva is an alternate biological matrix for drug testing that has several advantages over more traditional fluids such as blood and urine. Collection is rapid, noninvasive, and relatively easy to obtain. Several reports have detailed the appearance of drugs of abuse in saliva, but few have compared the excretion profiles of drugs administered by different routes. In this study, subjects were administered three smoked and three intravenous doses of heroin in an ascending dose design. Blood and saliva were collected periodically after drug administration and analyzed by gas chromatography-mass spectrometry (GC-MS) for heroin, 6-acetylmorphine, and morphine. In a second study, subjects were administered a single, smoked dose of 40 mg cocaine base and an intravenous dose of 44.8 mg cocaine HO on separate occasions. Plasma and saliva were collected and analyzed by CC-MS for cocaine, anhydroecgonine methyl ester (AEME), and seven additional metabolites. Heroin and 6-acetylmorphine were detected in the first saliva sample collected (2 min) following drug administration by both routes. Peak heroin concentrations were achieved quickly, between 2 and 5 min after intravenous administration and at 2 min after smoke heroin. Peak heroin concentrations in saliva after smoking heroin base ranged from 3534 (2.6 mg) to 20,580 ng/mL (5.2 mg), and after intravenous administration, concentrations ranged from 6 (10 mg heroin HCl to 30 ng/mL (12 mg heroin HCl. Saliva concentrations of heroin declined rapidly after intravenous administration, reaching the limit of sensitivity of the assay (1 ng/mL) by 60 min. Heroin concentrations in saliva after smoking declined slowly; detection times ranged from 4 to 24 h. Cocaine was the major analyte detected in saliva and plasma after smoked and intravenous administration. Peak saliva cocaine concentrations after intravenous administration ranged from 428 to 1927 ng/mL (N = 7); after smoking, they ranged from 15,852 to 504,880 ng/mL (N = 7). Peak plasma cocaine concentrations after intravenous administration ranged from 122 to 442 ng/mL A = 7), and after smoking, concentrations ranged from 46 to 291 ng/mL A = 7). The thermal degradation product of cocaine, AEME, was detected in saliva but not in plasma after smoking. Peak saliva AEME concentrations were achieved at 2 min and ranged from 558 to 4374 ng/mL (N = 7). These are the first reported observations of heroin and metabolites in saliva following heroin smoking and of AEME in saliva after smoking cocaine base. The presence of AEME in saliva may be useful as a marker of the smoked route following cocaine administration.

Administration, Inhalation↗

Associations between weight loss-induced changes in plasma organochlorine concentrations, serum T(3) concentration, and resting metabolic rate.

Organochlorine compounds are released from body fat into the bloodstream during weight loss. Because these compounds may impair thyroid status, which is implicated in the control of resting metabolic rate (RMR), the aim of this study was to determine if the augmentation in plasma organochlorine concentrations might be associated with the decrease in serum T(3) concentration and RMR observed in response to body weight loss. Plasma organochlorine concentrations, serum T(3) concentration, and RMR were measured before and after weight loss in 16 obese men who followed a nonmacronutrient-specific energy-restricted diet for 15 weeks. As expected, a significant decrease in serum T(3) concentration and RMR was observed after the program, whereas concentrations of most detected organochlorines were significantly increased. Changes in organochlorine concentrations were negatively associated with changes in serum T(3) concentration (significantly for p,p'-DDT, HCB, Aroclor 1260, PCB 28, PCB 99, PCB 118, and PCB 170) and with changes in RMR adjusted for weight loss (significantly for HCB and PCB 156). In conclusion, organochlorines released in plasma during weight loss are associated with the documented decrease in serum T(3) concentration and RMR. Further studies are needed to verify whether these findings are causally related.

Basal Metabolism↗

Interactions of valproic acid with carbamazepine and its metabolites' concentrations, concentrations ratios, and level/dose ratios in epileptic children.

In two groups of epileptic children receiving carbamazepine (CBZ) therapy with or without valproic acid (VPA) comedication, we investigate the drug interactions of VPA on serum CBZ and its metabolites' concentrations, concentration ratios, and level/dose ratios. Serum total and free CBZ-10, 11-epoxide (CBZ-E) concentrations are significantly increased in patients taking CBZ plus VPA, together with higher CBZ-E/CBZ concentration ratios and CBZ-E level/dose ratios. These results reflect the accumulation of CBZ-E. The decreased concentration ratios of trans-10, 11-dihydroxy-10, 11-dihydro-CBZ (CBZ-H)/CBZ-E observed in patients taking CBZ plus VPA suggest an inhibition in the biotransformation from CBZ-E to CBZ-H. Significant negative correlations are found between serum VPA level and CBZ-H/CBZ-E concentration ratios, indicating that the inhibition of CBZ-E hydrolysis by VPA may depend on the concentration of VPA (total or free CBZ-H/CBZ-E concentration ratio = [formula: see text], respectively). VPA concentration also shows significant positive correlations with CBZ-E and CBZ level/dose ratios. Patients taking CBZ plus VPA have significant higher free fractions of CBZ and CBZ-E than do patients on CBZ alone, suggesting a protein-binding displacement by VPA.

Carbamazepine↗

Concentrations of phosphorylated zidovudine (ZDV) in patient leukocytes do not correlate with ZDV dose or plasma concentrations.

Zidovudine (ZDV) elicits its antiviral effect through intracellular metabolism to the 5'-triphosphate, which interferes with viral replication. Monitoring of the active metabolites of ZDV in cells could lead to an intracellular therapeutic range. This study was performed to determine whether a radioimmunoassay, previously used for in vitro quantitation of total phosphorylated ZDV inside peripheral blood leukocytes, could be used for similar determinations in patient samples. The relationship between ZDV dose, plasma concentrations, and intracellular metabolite concentrations was also examined. Ten-milliliter blood samples were drawn from each of 13 human immunodeficiency virus-infected patients and were assayed. Intracellular concentrations of phosphorylated ZDV ranged from 0.33 to 3.54 pmol/10(6) cells, similar to those observed in vitro. Phosphorylated ZDV was independent of dose, and did not correlate with plasma concentrations. Intracellular concentration in the patient population as a whole did not change during the 4-h dosing interval, while plasma concentration decayed normally. Later determinations in the same patients gave intracellular values within 31% of earlier values. Intraassay variability was less than 10%. Thus, the method is valid for measurement of phosphorylated ZDV in patient cells. Although individual concentrations showed no clear change during the 3-month study period, intracellular concentrations decreased with increasing length of therapy (up to 3 years) in the population as a whole. This suggests a decreased cellular ability to phosphorylate ZDV after prolonged exposure to drug. The lack of intracellular decay implies a half-life longer than the 1-h half-life of plasma ZDV. These data suggest that smaller doses or longer dosing intervals might maintain intracellular concentrations once steady state is achieved.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Intracellular cytosolic free calcium concentration in the macula densa and in ascending limb cells at different luminal concentrations of sodium chloride and with added furosemide.

The juxtaglomerular apparatus fulfils several important regulatory functions in the kidney, such as tubuloglomerular feedback (TGF) control and control of renin release. The macula densa (MD) cells sense the fluid load by perceiving the distal NaCl concentration via a Na-K-2Cl cotransport system in the luminal cell membrane. It has been proposed that macula densa cell activation may involve changes in intracellular cytosolic free calcium concentration ([Ca2+]i), as one link in the chain of events activating TGF or releasing renin. We therefore investigated the changes in the intracellular calcium concentrations with fura-2, using a video system, in macula densa cells, and compared them with the changes in the corresponding concentrations in the ascending limb of the loop of Henle (c-TAL). The results show that our technique for analysing intracellular cytosolic free calcium in isolated perfused tubules is valid for this purpose, and the Kd value obtained was similar to that found by Grynkiewicz et al. (1985). The intracellular cytosolic free calcium concentration was about 90 nM both in the macula densa and c-TAL cells, and the macula densa cell intracellular cytosolic free calcium concentration increased by about 20 nM when the tubular lumen was perfused with Na and Cl at low concentrations. No significant changes were noted when furosemide was added to the perfusion solutions. We consider it hardly likely that this small change in intracellular cytosolic free calcium concentration can be entirely responsible for full activation of renin release or full inactivation of the TGF control mechanism. It would seem that the signal transmission from the macula densa cells could occur by other routes than through activation of intracellular cytosolic free calcium concentration.

Animals↗

Effects of increased blood ammonia concentrations on the concentrations of some metabolites in rat tissues.

Rats were given ammonium chloride intravenously (5 and 10 mg per 100 g body weight) and sacrificed 30 sec, 5 min and 30 min after injection. Ammonia concentrations were determined in brain, liver, skeletal muscle and epididymial fat, and glycogen, glucose, pyruvate, lactate, ATP and cyclic AMP were assayed in brain, liver and muscle. In control animals, muscle and fat showed a high capacity for ammonia accumulation. After injection of NH4Cl the ammonia concentration increased in all tissues analysed, particularly in muscle and fat, where ammonia concentrations remained elevated for 30 min. In brain, glycogen was reduced whereas glucose, pyruvate, lactate and cyclic AMP levels were raised. In liver, glycogen was lower and glucose higher than in controls. ATP concentrations were unchanged in both tissues. In muscle samples taken 30 sec and 5 min after dosing, glycogen concentrations were not affected but glucose, pyruvate and lactate concentrations were reduced and ATP concentrations were increased. In muscle samples taken after 30 min metabolite concentrations were normal again but glycogen concentrations had dropped.

Adenosine Triphosphate↗

Effects of changes in acid base and calcium concentration on fasting serum insulin, proinsulin, and glucose concentrations.

AIMS: To test the hypothesis that alterations in acid base or calcium concentration may affect proinsulin processing or the insulin secretion mechanism. METHODS: Changes in proinsulin secretion or cleavage were assessed by measuring serum intact proinsulin and immunoreactive insulin concentrations in three models of acid base and calcium disturbance: (1) subacute changes in acid base status in six volunteers who received oral placebo, ammonium chloride, or sodium bicarbonate for three five day periods; (2) acute changes in calcium concentration in eight subjects who received 25 mmol oral calcium; (3) chronic changes in calcium concentration in seven patients with primary hyperparathyroidism and five with pseudohypoparathyroidism. RESULTS: Acid base changes were confirmed by rises in serum bicarbonate concentrations (p < 0.01). No changes in serum insulin, intact proinsulin, or the proinsulin:insulin molar ratio were found. Serum calcium concentrations increased (2.49 v 2.38 mmol/l; p < 0.05) and parathyroid hormone concentrations decreased (1.1 v 1.9 pmol/l; p < 0.01) two hours after acute calcium loading. There were no significant differences in serum glucose, insulin, or intact proinsulin concentrations. Fasting proinsulin concentrations were significantly lower in the hyperparathyroid group (1.1 v 2.1 pmol/l; p < 0.05) and increased significantly after parathyroidectomy (2.1 v 1.1 pmol/l; p < 0.05). CONCLUSIONS: The results indicate that subacute acid base changes do not affect proinsulin cleavage. Although acute calcium loading has no demonstrable effect, chronic hypercalcaemia may influence the mechanism of insulin secretion.

Acid-Base Equilibrium↗

Longitudinal study of workers exposed to mercury vapour at low concentrations: time course of inorganic and organic mercury concentrations in urine, blood, and hair.

Seven Japanese female workers exposed to mercury vapour at a concentration of < 0.02 mg Hg/m3 (8 h/day, 44 h/week) were examined for inorganic (I-Hg) and organic (O-Hg) mercury concentrations in urine, blood, and hair after 0, 4, 8, 17, and 23 months of exposure. Both I-Hg and O-Hg concentrations in urine and hair did not increase significantly even after 23 months of exposure. The concentration of I-Hg and O-Hg in plasma and O-Hg in erythrocytes, however, increased significantly after four months of exposure, and the high concentrations were maintained until the end of the study (23 months of exposure). Absence of a significant increase in the concentration of O-Hg in hair indicates that changes in concentrations of I-Hg and O-Hg in blood could be caused by the occupational exposure to mercury vapour. These results show clearly that mercury concentration in blood indicates the uptake of mercury compared with data from before employment with mercury. Even after 23 months of exposure to mercury vapour, however, urinary mercury concentration was not affected.

Adult↗

Regulation of internal solute concentrations of marine Vibrio alginolyticus in response to external NaCl concentration.

Slightly halophilic marine Vibrio alginolyticus grown in the range of NaCl from 0.2 to 1.5 M maintained the total internal solute concentration always higher than the external medium by about 0.25 osM. The concentrations of macromolecules such as DNA, RNA, and protein were little affected by the increase in medium NaCl. The internal K+ concentration was kept to about 400 mM in the range of medium NaCl from 0.4 to 0.8 M; it rose to 510 mM when the bacterium was grown in 1.5 M NaCl, indicating that K+ increased only slightly in response to the large increase in medium NaCl. Thus, in contrast to the case of nonhalophilic and extremely halophilic bacteria, K+ was unlikely to act as a major component to regulate the internal solute concentration of marine V. alginolyticus. The internal Na+ and Cl- concentrations were maintained always lower than those in the growth medium, but they increased in response to the increase in medium NaCl. The concentration of internal Na+ was close to that of K+ at the concentration of medium NaCl that supports the optimal growth of this organism. The total amino acid content of V. alginolyticus increased from 76 to 413 mM by the increase in medium NaCl from 0.2 to 1.5 M. The concentrations of glutamic acid and prolined were 254 and 72 mM, respectively, when grown in 1.5 M NaCl. These results indicated that Na+, Cl- and amino acids, especially glutamic acid and proline, contributed to the regulation of internal solute concentration of V. alginolyticus in response to the increased external NaCl.

Amino Acids↗

Relationship between amylase concentration, L/S ratio and lecithin concentrations in amniotic fluid.

Amylase concentration, L/S ratio and lecithin concentration were measured in 110 samples of amniotic fluid in 106 uneventful pregnancies. Amylase concentrations lower than 200 U/l corresponded significantly (p less than 0.001) to a gestational age less than the 37th week as well as to a L/S ratio lower than 2 and to lecithin concentrations lower than 3.5 mg%. Furthermore, amylase values higher than 300 U/l corresponded significantly (p less than 0.001) to a gestational age over the 37th week as to an L/S ratio over 2 and to lecithin concentrations over 3.5 mg%. On the other hand amylase concentrations ranging between 200 and 300 U/l failed to show any significant relationship neither to the age of gestation nor to the concentration of phospholipids. These findings show that the amylase test is a useful method for prediction of fetal maturity. Since the procedure of determination of the amylase concentration is very simple, cheap and rapid, the test can be used as screening method. However, when amylase concentrations are found to range between 200 and 300 U/l specific tests for assessment of fetal maturity have to be applied.

Amniotic Fluid↗

Steady state model of 3,5,3'-triiodothyronine transport in liver predicts high cellular exchangeable hormone concentration relative to in vitro free hormone concentration.

The hepatic nuclear receptor for T3 is known to be approximately 50% saturated in vivo. Since the receptor dissociation constant (Kd) is 1 nM, and since 50% receptor occupancy occurs when the concentration of free ligand in the nucleus is 1 nM, the concentration of free T3 in the hepatic nucleus is also approximately 1 nM or about 200-fold greater than the concentration of free T3 in human serum, as measured in vitro by equilibrium dialysis. However, previous tracer kinetic studies have shown that T3 is available for transport from both the circulating albumin- and thyroid hormone-binding globulin-bound pools in plasma. Since the plasma proteins per se do not significantly exit the hepatic microcirculation on a single pass, the protein-bound hormone is operationally available for transport into liver via a proposed mechanism of enhanced dissociation caused by interactions between the plasma proteins and the hepatic microcirculation. These considerations raise the question as to whether the dissociation of T3 from serum proteins is sufficiently enhanced to allow for enrichment in the hepatic pools of exchangeable hormone that can generate 50% receptor occupancy. The present studies present a physiologically based steady state model of T3 transport and distribution in liver. All parameters of the model pertain to physiologically discrete pathways of hormone, plasma protein, or plasma flux through the liver. The rate constants were estimated from previously reported tracer kinetic transport data in rat liver in vivo using rat and human serum proteins. A computer program in BASIC for steady state analysis is presented. The results of the stimulation studies are as follows. The concentration of cellular exchangeable T3 in liver is predicted to be approximately 2 log orders greater than the concentration of free T3 measured in vitro, but approximately equal to the concentration of free T3 predicted to exist in the hepatic nucleus; thus, the high degree of hepatic nuclear T3 receptor occupancy is compatible with the model that T3 is available for transport into liver from the circulating serum protein-bound pools. The concentration of cellular exchangeable T3 is governed primarily by the concentration of plasma exchangeable T3 (and membrane transport and cellular metabolism of T3) and is predicted to be independent of changes in the concentration of cytosolic T3-binding proteins.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Atazanavir plasma concentrations vary significantly between patients and correlate with increased serum bilirubin concentrations.

BACKGROUND: Atazanavir (ATV) is recommended to be dosed at 400 mg once daily or 300 mg daily coadministered with 100 mg ritonavir (RTV). METHOD: 31 male patients receiving ATV either alone or boosted with RTV for more than 2 weeks had ATV concentration measured by high performance liquid chromatography (HPLC). ATV concentrations were adjusted to obtain a 24-hour trough level using a standard pharmacokinetic formula. RESULTS: 25 samples were taken from patients who received 300 mg ATV, 6 with 200 mg, 3 with 400 mg, and 2 with 150 mg, all boosted with 100 mg RTV. In the unboosted group, patients received 400 mg (7) or 600 mg (2). The median adjusted 24-hour trough ATV concentration was 630 ng/mL (interquartile range [IQR] 355-1034) in the boosted and 113 ng/mL (IQR 50-225) in the unboosted group (p = .001). Median serum bilirubin concentration was 34 IU/L (IQR 27.5-49) and 41 IU/L (IQR 31-45) in the boosted and unboosted groups, respectively. In the boosted group, high ATV concentrations were significantly correlated with increased serum bilirubin concentrations (p = .003). CONCLUSION: ATV concentrations showed considerable interpatient variability. Bilirubin concentrations are an indicator of high ATV concentrations and may prove to be useful in selecting patients for therapeutic drug monitoring (TDM).

Atazanavir Sulfate↗

Effect of oestradiol replacement in ovariectomized chickens on pituitary LH concentrations and concentrations of mRNAs encoding LH beta and alpha subunits.

Plasma concentrations of oestradiol and LH and steady-state pituitary concentrations of the mRNAs encoding the LH beta and alpha subunits in the gland were measured at intervals of 1 month for 5 months in female chickens. In addition, feedback regulation by oestradiol of concentrations of mRNAs encoding these LH subunits was studied in ovariectomized young (3-week-old) and adult hens. Concentrations of the mRNAs encoding the LH beta and alpha subunits increased significantly before sexual maturity and the changes were highly correlated with increases in plasma and pituitary concentrations of LH. Ovariectomy significantly reduced circulating plasma concentrations of oestradiol but increased pituitary concentrations of mRNAs encoding LH beta and alpha subunits and pituitary and plasma concentrations of LH in adult laying hens. In addition, in 3-week-old chickens, ovariectomy induced an increase in plasma and pituitary gland concentrations of LH. This ovariectomy-induced mRNA expression and tissue and plasma increases of LH were prevented by oestradiol replacement. These data suggest that a negative feedback mechanism by ovarian oestradiol inhibits LH release from the pituitary and pituitary LH biosynthesis in chickens.

Animals↗

Prediction of serum ionized calcium concentration by use of serum total calcium concentration in dogs.

OBJECTIVE: To determine whether total serum calcium (tCa) or adjusted tCa concentrations accurately predict ionized calcium (iCa) status in dogs. SAMPLE POPULATION: 1,633 canine serum samples. PROCEDURE: The tCa concentration was adjusted for total protein (TP) or albumin concentration by use of published equations. Correlations between iCa and tCa or adjusted tCa, tCa and TP, and tCa and albumin were calculated. Diagnostic discordance between tCa or adjusted tCa and iCa was determined. Diagnostic discordance in predicting iCa was also determined for 490 dogs with chronic renal failure (CRF). Sensitivity, specificity, positive and negative predictive values, and positive and negative diagnostic likelihood ratios were calculated for tCa, tCa adjusted forTP, and tCa adjusted for albumin. RESULTS: Diagnostic discordance was 27% when tCa concentration was used to predict iCa status. Use of adjusted tCa increased diagnostic discordance to approximately 37% for all dogs and 55% for dogs with CRF. Positive predictive value and positive diagnostic likelihood ratios were poor when tCa concentration was used to predict iCa status. The tCa concentration overestimated normocalcemia and underestimated hypocalcemia. Adjusted tCa overestimated hypercalcemia and underestimated hypocalcemia. CONCLUSIONS AND CLINICAL RELEVANCE: Adjusted tCa or tCa concentrations are unacceptable for predicting iCa status in dogs. Use of adjustment equations is not recommended. Direct measurement of iCa concentration is necessary for accurate assessment of calcium status. Use of tCa or adjusted tCa concentrations to predict iCa status in dogs could cause serious mistakes in diagnosis and case management, especially in dogs with CRF.

Animals↗

Influence of a gonadotropin-releasing hormone agonist on circulating concentrations of luteinizing hormone and testosterone and tissue concentrations of compounds associated with boar taint.

Twenty-four Yorkshire boars and six barrows approximately 8 mo of age were used to evaluate the effects of a GnRH agonist (GnRH-A) on circulating concentrations of LH and testosterone (T), concentrations of skatole in fat, and concentrations of 16-androstene steroids in fat and salivary glands. Pigs were assigned to five groups of six pigs each: L200, boars injected with 200 micrograms of GnRH-A/kg BW; L50, boars injected with 50 micrograms of GnRH-A/kg BW; Boar, boars treated with vehicle; Castrate, males castrated on the same day that Groups 1 to 3 received injections; and Barrow, males castrated as neonates. Pigs in L200, L50, and Boar were only given one injection. Blood samples were taken twice daily from d -2 to 28 for determinations of T and LH concentrations and at 15-min intervals for 6 h on d -1, 1, 7, 14, 21, and 28 for characterization of pulsatile LH release. Pigs were slaughtered on d 30, and samples of backfat and salivary glands were collected for quantification of skatole and 16-androstene steroid concentrations. The LH concentrations increased immediately following GnRH-A injection in L200 and L50 (P < .001) and then declined to pretreatment values by approximately 29 h after treatment. Serum T concentrations in L200 and L50 increased after GnRH-A treatment (P < .0001) and then decreased to less than pretreatment concentrations by d 5 in L200 (P < .001) and by d 8 in L50 (P < .01). Concentrations of 16-androstene steroids in fat were less (P < .05) in L200 and Barrow than in Boar.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗

Genetic parameter estimates for serum insulin-like growth factor I concentrations, and body weight and weight gains in Angus beef cattle divergently selected for serum insulin-like growth factor I concentration.

Data for the current study were obtained from a divergent selection experiment in which the selection criterion was the average serum IGF-I concentrations of 3 postweaning blood samples collected from purebred Angus calves. Multiple-trait derivative-free REML procedures were used to obtain genetic parameter estimates for IGF-I concentrations and for BW and BW gains measured from birth to the conclusion of a 140-d postweaning performance test. Included in the analysis were 2,674 animals in the A(-1) matrix, 1,761 of which had valid records for IGF-I concentrations. Direct heritability estimates +/- SE for IGF-I concentration at d 28, 42, and 56 of the postweaning period and for mean IGF-I concentrations were 0.44 +/- 0.07, 0.51 +/- 0.08, 0.42 +/- 0.07, and 0.52 +/- 0.08, respectively. Heritability estimates for maternal genetic effects ranged from 0.10 +/- 0.05 to 0.20 +/- 0.06. The proportion of total phenotypic variance due to the maternal permanent environmental effect was essentially zero for all measures of IGF-I concentrations. Genetic correlations of IGF-I concentrations with weaning and post-weaning BW ranged from 0.07 +/- 0.12 to 0.32 +/- 0.11 and generally demonstrated an increasing trend during the postweaning period. Averaged across the various measures of IGF-I, the genetic correlation of IGF-I with preweaning gain was 0.14, whereas the genetic correlation with postweaning gain was 0.29. Genetic correlations between IGF-I and BW gain were positive during all time intervals, except between weaning and the beginning of the postweaning test and from d 84 to 112 of the postweaning period. Environmental and phenotypic correlations of IGF-I with BW and BW gains were generally positive, but small. These results indicate that postweaning serum IGF-I concentration is moderately to highly heritable and has small positive genetic, environmental, and phenotypic correlations with BW other than birth weight and with pre- and postweaning gain. Therefore, if IGF-I proves to be a biological indicator of an economically important trait (e.g., efficiency of feed use for growth) in beef cattle, it should be possible to rapidly change IGF-I concentrations via selection without significantly altering live weight or rate of gain.

Aging↗

[Relationship between changes in estimated and measured blood concentrations of propofol and serum albumin concentration during propofol anesthesia: effects of intraoperative bleeding (a case report)].

We investigated the effect of intraoperative bleeding on the changes in estimated and measured blood concentrations of propofol, and the relationship between anesthetic effect of propofol and serum albumin concentration in a patient undergoing prostatectomy during propofol/epidural anesthesia. The rate of propofol infusion was titrated to keep the BIS value about 50. The estimated blood concentration of propofol calculated by ConGrase, a program for on-line simulation of blood propofol concentration, was monitored during anesthesia. Blood samples were obtained at nine points during surgery and the blood concentrations of propofol and albumin were measured postoperatively. When the amount of bleeding reached about 2000 mg, the difference between estimated and measured blood concentrations of propofol did not increase. As the serum albumin concentration decreased, the concentration of propofol to keep bispectral index about 50 decreased. This study suggests that the change in serum albumin concentration following intraoperative bleeding is an important factor in the anesthetic effect of propofol.

Aged↗

Influence of total lipid concentration, bile salt:lecithin ratio, and cholesterol content on inter-mixed micellar/vesicular (non-lecithin-associated) bile salt concentrations in model bile.

We modified classic equilibrium dialysis methodology to correct for dialysant dilution and Donnan effects, and have systematically studied how variations in total lipid concentration, bile salt (taurocholate):lecithin (egg yolk) ratio, and cholesterol content influence inter-mixed micellar/vesicular (non-lecithin-associated) concentrations (IMC) of bile salts (BS) in model bile. To simulate large volumes of dialysant, the total volume (1 ml) of model bile was exchanged nine times during dialysis. When equilibrium was reached, dialysate BS concentrations plateaued, and initial and final BS concentrations in the dialysant were identical. After corrections for Donnan effects, IMC values were appreciably lower than final dialysate BS concentrations. Quasielastic light scattering was used to validate these IMC values by demonstrating that lipid particle sizes and mean scattered light intensities did not vary when model biles were diluted with aqueous BS solutions of the appropriate IMC. Micelles and vesicles were separated from cholesterol-supersaturated model bile, utilizing high performance gel chromatography with an eluant containing the IMC. Upon rechromatography of micelles and vesicles using an identical IMC, there was no net transfer of lipid between micelles and vesicles. To simulate dilution during gel filtration, model biles were diluted with 10 mM Na cholate, the prevailing literature eluant, resulting in net transfer of lipid between micelles and vesicles, the direction of which depended upon total lipid concentration and BS/lecithin ratio. Using the present methodology, we demonstrated that inter-mixed micellar/vesicular concentrations (IMC) values increased strongly (5 to 40 mM) with increases in both bile salt (BS):lecithin ratio and total lipid concentration, whereas variations in cholesterol content had no appreciable effects. For model biles with typical physiological biliary lipid compositions, IMC values exceeded the critical micellar concentration of the pure BS, implying that in cholesterol-supersaturated biles, simple BS micelles coexist with mixed BS/lecithin/cholesterol micelles and cholesterol/lecithin vesicles. We believe that this methodology allows the systematic evaluation of IMC values, with the ultimate aim of accurately separating micellar, vesicular, and potential other cholesterol-carrying particles from native bile.

Bile↗