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PubMed1997

Serum leptin concentrations correlate to plasma insulin concentrations independent of body fat content in chronic renal failure.

BACKGROUND: The ob gene product leptin is secreted by fat cells and reflects the content of fat in the body. Leptin and insulin concentrations as well as body weight are interrelated and a direct correlation has been found between these concentrations in humans with normal renal function. Markedly elevated serum leptin concentrations have recently been reported in patients with chronic renal failure (CRF). The aim of the present study was to investigate the relation between serum leptin and plasma insulin in patients with advanced CRF. METHODS: Serum leptin, plasma insulin, as well as body fat content (determined with dual-energy X-ray absorptiometry) were determined in a cohort of 46 patients (mean age 54 +/- 2 years) with advanced CRF (creatinine clearance 8 +/- 1 ml/min). RESULTS: In 23 CRF patients with plasma insulin below the median value (14 mU/l), serum leptin concentrations were no higher than in healthy controls (8.0 +/- 1.2 vs 8.4 +/- 0.9 ng/ml). However, in CRF patients with plasma insulin > 14 mU/l (n = 23) the serum leptin concentrations were much higher (38.2 +/- 11.0 ng/ml; P < 0.0001). In CRF patients, serum leptin (normalized for the per cent body fat content) correlated significantly (r = 0.64; P < 0.0001) with plasma insulin concentrations. However, the increase in plasma insulin was blunted in patients with very high serum leptin concentrations in relation to the per cent body fat content. CONCLUSIONS: The present results demonstrate that serum leptin concentrations are markedly elevated in CRF patients with higher plasma insulin than in those with lower plasma insulin concentrations. This suggests that insulin resistance and hyperinsulinaemia contribute to elevated serum leptin concentrations in CRF. The present results also demonstrate that, when circulating serum leptin concentrations are much higher in relation to the per cent body fat content, no additional increase in plasma insulin occurs. This latter observation suggests that the secretion of insulin by the pancreas is lower in hyperleptinaemic patients. Consequently, extremely elevated serum leptin may play a role in reducing glucose-stimulated insulin secretion and glucose intolerance in CRF.

Adipose Tissue↗

PubMed1997

Effects of foliar potassium concentration on morphology, ultrastructure and polyamine concentrations of Scots pine needles.

We examined the effects of three foliar potassium concentrations (high, intermediate and low) on the morphology, ultrastructure and polyamine concentrations of current-year and 1- and 2-year-old needles of 30-year-old Scots pine (Pinus sylvestris L.) trees. Foliar K concentration had only a slight effect on needle morphology. The sclerenchyma cell walls were thinner, the xylem area was larger, and the resin ducts were smaller in needles with a low K concentration than in needles with a high or intermediate K concentration. In addition, the bundle sheath cells were collapsed in needles having a low K concentration. The secondary growth of phloem tissue and the mesophyll area were greater in needles with a high or intermediate K concentration than in needles with a low K concentration, possibly indicating greater production of photoassimilates in these trees. At the ultrastructural level, mesophyll cells with enlarged central vacuoles and small vacuoles containing electron-dense material were common in needles having a low K concentration. Enlargement of the central vacuole coincided with an exponential increase in putrescine concentration in needles with a low K concentration, suggesting that the central vacuole may function as a storage site for putrescine.

Journal Article↗

PubMed2001

Plasma concentration of topiramate correlates with cerebrospinal fluid concentration.

The authors examined the ratio between the plasma and the cerebrospinal fluid (CSF) concentration of topiramate in 14 adults with epilepsy. Simultaneous trough samples of venous blood and CSF were collected and analyzed as total and unbound concentrations. Concomitant levels were also analyzed of lamotrigine (n = 5) and the relevant oxcarbazepine metabolite, 10-hydroxycarbazepine (n = 3). There was a close correlation between the plasma and the CSF concentration for both the total and unbound concentration of topiramate. The median CSF/plasma ratio of total topiramate was 0.85. The free topiramate concentration in plasma was not different from the free topiramate concentration in CSF. The CSF/plasma ratios showed little variation and were independent of the plasma level for both the total and the unbound levels. The unbound fraction of topiramate was 84% in plasma and 97% in CSF. The CSF concentrations of lamotrigine and 10-hydroxycarbazepine were 50% and 61% of the plasma concentrations, respectively. For topiramate, there is a close correlation between the plasma concentration and the CSF concentration. There does not seem to be a saturable carrier mechanism restricting topiramate transport across the blood-brain barrier. The concentration of topiramate in CSF is equal to the unbound proportion of topiramate in plasma, implying that the delivery of topiramate to the brain occurs via transfer from the unbound plasma pool. Plasma is thus a relevant matrix for therapeutic drug monitoring of topiramate.

Adolescent↗

PubMed1999

Peak and trough growth hormone (GH) concentrations influence growth and serum insulin like growth factor-1 (IGF-1) concentrations in short children.

OBJECTIVE: Growth hormone (GH) is secreted in a pulsatile fashion promoting growth and a number of diverse metabolic actions. The precise components of the pulsatile signal involved in growth regulation are unclear. DESIGN: A retrospective analysis of 24 h serum GH concentration profiles to evaluate the relative contribution of peak and trough serum GH concentrations to growth regulation, GH response to insulin induced hypoglycaemia (ITT) and serum insulin like growth factor-1 (IGF-1) concentration. PATIENTS: Fifty short prepubertal children (age 5.2-11.9 years). MEASUREMENT: Analysis of the hormone profile by a concentration distribution method that determines the concentration at or below which the serum GH concentrations in the 24 hour profile spend a percentage of the total time. The method generates an estimate of the observed concentrations (OC) below which 95% and 5% of the values in the time series lie: OC 95 (peaks) and OC5 (troughs). RESULTS: Twenty six of the children were growing at a normal rate for short children with a height velocity standard deviation score (HVSDS) between +0.4 and -0.8 whereas twenty four were growing more slowly (HVSDS between -0.9 to -3.9). The former group had a mean peak GH response to ITT of 27.3 (11.1) mU/l whereas the latter had a mean value of 8.7 (6.5) mU/l. There was no relationship between (peak and trough GH concentration) and the age of the individual or body mass index. Peak GH levels were positively related to HVSDS and serum IGF-1 values (r = 0.44; P = 0.002 and r = 0.53; P = 0.002, respectively). GH trough levels were inversely related to these measurements (r = -0.29; P = 0.05; and r = -0.46; P = 0.002, respectively). Further analysis showed that individuals with the slowest growth rates and lowest IGF-1 concentrations had the lowest peak and highest trough GH concentrations (ANOVA F = 6.0; P = 0.002). Similarly, the peak GH response to ITT was lowest in those individuals with high troughs and low peaks (ANOVA F = 9.99; P < 0.001). CONCLUSIONS: These results suggest that the peak values of a GH concentration profile influence growth rate and the IGF-1 axis whereas elevated trough values have the greatest influence on growth rate and IGF-1 values when GH peaks are low.

Analysis of Variance↗

PubMed2004

Determination of threshold concentrations of allergens and evaluation of two different histamine concentrations in canine intradermal testing.

The purpose of this study was to determine the optimal histamine concentration and allergen threshold concentrations for canine intradermal testing. Thirty healthy dogs were tested using two different concentrations of histamine and four different concentrations of each allergen. The optimal histamine concentration was determined to be 1:10 000 w/v. The threshold concentration was at least 1750 PNU/mL for all tested grasses, weeds, trees, moulds and insects, except for fleas which was as least 1:500 w/v. For Dermatophagoides pteronyssinus, the optimal threshold concentration was 250 PNU/mL, whereas for Dermatophagoides farinae and Tyrophagus putrescentiae, it was 100 PNU/mL. Threshold concentration for all epidermals except human dander was at least 1250 PNU/mL. The optimal threshold concentration for human dander was 300 PNU/mL. Our results suggest that the currently used 1:100 000 w/v concentration of histamine and the 1000 PNU/mL concentration for most grasses, weeds, trees, moulds, epidermals and insects may not be appropriate for canine intradermal testing.

Allergens↗

PubMed1996

Transformation of Low Concentrations of 3-Chlorobenzoate by Pseudomonas sp. Strain B13: Kinetics and Residual Concentrations.

The transformation of 3-chlorobenzoate (3CB) and acetate at initial concentrations in the wide range of 10 nM to 16 mM was studied in batch experiments with Pseudomonas sp. strain B13. Transformation rates of 3CB at millimolar concentrations could be described by Michaelis-Menten kinetics (K(infm), 0.13 mM; V(infmax), 24 nmol (middot) mg of protein(sup-1) (middot) min(sup-1)). Experiments with nanomolar and low micromolar concentrations of 3CB indicated the possible existence of two different transformation systems for 3CB. The first transformation system operated above 1 (mu)M 3CB, with an apparent threshold concentration of 0.50 (plusmn) 0.11 (mu)M. A second transformation system operated below 1 (mu)M 3CB and showed first-order kinetics (rate constant, 0.076 liter (middot) g of protein(sup-1) (middot) min(sup-1)), with no threshold concentration in the nanomolar range. A residual substrate concentration, as has been reported for some other Pseudomonas strains, could not be detected for 3CB (detection limit, 1.0 nM) in batch incubations with Pseudomonas sp. strain B13. The addition of various concentrations of acetate as a second, easily degradable substrate neither affected the transformation kinetics of 3CB nor induced a detectable residual substrate concentration. Acetate alone also showed no residual concentration (detection limit, 0.5 nM). The results presented indicate that the concentration limits for substrate conversion obtained by extrapolation from kinetic data at higher substrate concentrations may underestimate the true conversion capacity of a microbial culture.

Journal Article↗

PubMed2005

Calibration models for the vinyl acetate concentration in ethylene-vinyl acetate copolymers and its on-line monitoring by near-infrared spectroscopy and chemometrics: use of band shifts associated with variations in the vinyl acetate concentration to improve the models.

The present study investigates calibration models for the vinyl acetate (VA) concentration in ethylene-vinyl acetate (EVA) copolymers and its on-line monitoring by near-infrared (NIR) spectroscopy and chemometrics. The key point in the present study is to make use of band shifts associated with concentration changes in the vinyl acetate (VA) for the improvement of the models. NIR spectra of EVA in melt and solid states were measured by a Fourier transform near-infrared (FT-NIR) on-line monitoring system and a FT-NIR laboratory system. Some of the bands in the NIR spectra for both states show significant shifts with the variations in the VA concentration. The peak shifts induced by the VA concentration changes are larger in the solid-state EVA than those in the melt-state EVA. We have developed calibration models for the VA concentration in the solid-state EVA and investigated how to improve the calibration models. The factor analysis of partial least squares (PLS) regression has suggested that the wavenumber shifts caused by the VA concentration changes affect the calibration models for the VA concentration in EVA. From the analysis, it has been proposed that the wavenumbers in the spectrum of one sample in nine EVA samples (VA concentration range: 0-41.1%) are shifted for the improvement of the calibration models, and the effects of the proposed method have been confirmed by using the PLS calibration models for the VA concentration in the solid EVA samples. As the next step, the effects of the wavenumber shift method have been explored for the calibration models for the VA concentration in the melt-state EVA. After that, the discrimination method using the score plots of PLS and the application sequence for the on-line monitoring to use the proposed wavenumber shift method were studied. The simulation results using the discrimination and wavenumber shift methods have shown that those methods are very effective to improve the predicted values of the calibration models for the on-line monitoring of the VA concentration in the melt-state EVA.

Algorithms↗

PubMed2004

Effect of supplemental vitamin D3 concentration on concentrations of calcium, phosphorus, and magnesium relative to protein in subcellular components of the longissimus and the distribution of calcium within longissimus muscle of beef steers.

The effect of supplementing diets with various levels of vitamin D3 to provide 0, 0.5, 1, and 5 million IU/(steer x d) for 8 d before slaughter on the mineral content and localization of Ca in LM and muscle fragments was studied during the postmortem aging process. Twelve feedlot steers of three biological types were given access to the four levels of vitamin D for 8 d before slaughter. Differential centrifugation techniques were used to determine the concentrations of minerals relative to protein in different muscle fragments on d 3 and 21 postmortem. Electron microscopy visualization of bound Ca indicated that vitamin D3 mobilized Ca from the sarcoplasmic reticulum and transverse tubule system into the myofibrils. Bound Ca was concentrated near the Z-line at the A-band/I-band juncture within the sarcomere. Supplementing steers with 1 and 5 million IU/(steer x d) of vitamin D3 increased (P < 0.05) Ca, P, and Mg concentrations per unit of protein in the cytosol. Soluble cytosolic Ca concentrations were greater (P < 0.05) on d 21 than on d 3 postmortem only when steers were supplemented with 5 million IU/d. Concentrations of Ca, P, and Mg in isolated tissues were increased (P < 0.05) in nuclei and myofibrilar proteins by supplementing steers with 1 and 5 million IU/ (steer x d) of vitamin D3. All supplemental vitamin D3 treatments also increased (P < 0.001) Mg concentrations in the cytosol, regardless of aging treatment, and increased Mg concentrations (P < 0.04) within the mitochondria at d 3 postmortem. Thus, supplementation of feedlot steers with vitamin D3 at levels of 0.5 to 5 million IU/(steer x d) increased Ca concentrations within respiring muscle, resulting in increased bound tissue Ca concentrations. When the respiring muscle was converted to meat, the increased bound tissue Ca resulting from vitamin D3 treatment released Ca concentrations into the cytosol during aging (P < 0.05). Results of this study indicate that vitamin D3 supplementation increased total cytosolic Ca, P, and Mg concentrations in meat.

Animals↗

PubMed1992

Bovine uterine, cervical and ovarian androgen receptor concentrations. Correlation with estrogen and progesterone receptor concentrations.

Bovine cytosol androgen receptor (ARC) concentrations were examined simultaneously in various regions of the uterus and in ovarian tissues of cows, and were related to cytosol estrogen (ERC) and progesterone receptor (PRC) concentrations and circulating steroid levels. ERC concentrations were 3-7-fold and PRC concentrations 13-29-fold those of ARC in bovine endometrial and myometrial tissues. When serum progesterone levels were low, both endometrial and myometrial ARC, endometrial ERC, and endometrial and myometrial PRC concentrations were higher (p < 0.05) than those observed during higher progesterone concentrations. Because serum 5 alpha-dihydrotestosterone (5 alpha-DHT) concentrations were higher during the luteal phase, it is possible that ARC was down-regulated by this natural ligand at this phase of the cycle. There were no differences between uterine horns in endometrial or myometrial ARC concentrations. Bovine cervical and ovarian stromal tissue also contained ARC, and the concentrations were about the same as in the endometrium and the myometrium. The relative binding affinities (RBAs) of some steroid hormones towards ARC in vitro were: the synthetic compound R1881 (146%), 5 alpha-dihydrotestosterone (100%), testosterone (75%) while estradiol-17 beta, progesterone and dexamethasone had lower RBAs (2, < 1, < 1% respectively). Cytosol androgen receptor concentrations correlated significantly with cytosol progesterone (PRC) and estrogen receptor (ERC) concentrations, both in the endometrium and myometrium. These data show that androgens, such as 5 alpha-DHT, may participate the endocrine regulation of bovine reproductive tissues.

Animals↗

PubMed1995

Antiarrhythmic effect related to the plasma concentration of pentisomide in vivo and the antiarrhythmic-concentration relationship in vitro.

Pentisomide, 2-(2-diisopropylaminoethyl)-4-methyl-2-(pyridyl)- pentanamide, is a novel antiarrhythmic agent structurally related to disopyramide. Using a glass bead arrhythmic model, the authors studied the antiarrhythmic effect of pentisomide in dogs by monitoring the plasma concentrations. When pentisomide was infused at 1 mg/kg/min for 20 min, the ventricular tachycardia was significantly reduced at 5 min after starting the infusion; the arrhythmias were reduced to less than 5% at the end of the 20 min infusion. The plasma-free concentration of pentisomide was about 3 micrograms/ml at 5 min; it increased to about 10 micrograms/ml at the end of 20 min infusion. With 0.3 mg/kg/min infusion, the arrhythmias were reduced to about 60% but were not significant at 20 min of infusion. The plasma-free concentration of pentisomide did not reach 3 micrograms/ml until 20 min of infusion. The 3 micrograms/ml plasma-free concentration for pentisomide seems to be a critical concentration in inducing a significant antiarrhythmic effect. Pentisomide dose-dependently inhibited ischaemia-reperfusion arrhythmia at doses of 30 microM and higher concentrations in vitro. In conclusion, pentisomide inhibits arrhythmias dependent with the plasma concentration or with the concentration of the external solution. The critical plasma-free concentration for inhibition of arrhythmias was 3 micrograms/ml (not equal to 10 microM) and the in vitro effect also had a similar concentration. Therefore, the in vivo and in vitro antiarrhythmic concentrations were well correlated.

Animals↗

PubMed1995

Naproxen concentrations in plasma and synovial fluid and effects on prostanoid concentrations.

OBJECTIVE: To test the hypothesis that unbound concentrations of naproxen in synovial fluid (SF) and plasma (P) are equal over a drug dosage interval at steady state or after a single dose of drug. The relationship between plasma and SF concentrations of naproxen, respectively, and prostaglandin concentrations were also examined. METHODS: Paired, sequential, total, and unbound naproxen concentrations were determined in plasma and SF in 2 groups of 6 patients. A single dose group was given naproxen 500 mg. The chronic dose group was given 500 mg bd for 7 days before collection of blood and SF samples. The effect of naproxen on prostanoid production by clotting whole blood (thromboxane B2, TXB2) and in SF (PGE2, 6-keto-PGF1 alpha) was determined by radioimmunoassay. RESULTS: Average area under the curve (AUC) of unbound (U) naproxen concentrations against time in plasma and SF were the same over a dosage interval at steady state (ratio AUCU,SF/AUCU,P, 1.12 +/- 0.18; p = 0.108), but not after a single acute dose (AUCU,SF/AUCU,P, 1.34 +/- 0.32; p = 0.044). Data from the single dose study revealed that the mean (+/- SD) of the concentrations required for 50% inhibition (EC50) of platelet derived TXB2 by total naproxen was 7.7 +/- 4.4 micrograms/ml (n = 5) and for unbound drug 25.4 +/- 22.0 ng/ml (n = 5). SF prostanoid concentrations after both acute and chronic dosing were low, as expected, but temporal and dose relationships of prostanoid concentrations with SF naproxen could not be discerned. However, this may reflect study design. CONCLUSIONS: The AUC of unbound naproxen in SF and plasma were similar at steady state. Plasma concentrations correlated with inhibition of TXB2 generation by platelets. There was sustained depression of PG concentrations in SF beyond the time suggested by plasma drug concentrations.

Adult↗

PubMedDate not supplied

Relation of fasting plasma insulin concentration to high density lipoprotein cholesterol and triglyceride concentrations in men.

Low plasma high density lipoprotein (HDL) cholesterol concentration is a risk factor for coronary heart disease (CHD) and is frequently associated with high triglyceride concentration. Both of these abnormalities have been related to insulin resistance as estimated by plasma insulin concentrations and to measures of obesity, regional adiposity, and physical fitness. To determine which of these variables (fasting plasma insulin, obesity as measured by body mass index [BMI], or regional adiposity as measured by waist to hip ratio [WHR]) best identifies men with low HDL cholesterol and high triglyceride concentrations, we divided 83 men, aged 50-65 years, who were free of CHD or diabetes, into tertiles based on BMI, WHR, or fasting plasma insulin concentration. Only for plasma insulin tertiles were there statistically significant differences in HDL cholesterol (tertile 1, mean +/- SEM, 1.34 +/- 0.08 mmol/l; 2, 1.16 +/- 0.05 mmol/l; 3, 1.10 +/- 0.06 mmol/l; p less than 0.03) and triglyceride (tertile 1, 1.05 +/- 0.08 mmol/l; 2, 1.48 +/- 0.12 mmol/l; 3, 1.82 +/- 0.17 mmol/l; p less than 0.005) concentrations. In forward stepwise regressions with HDL cholesterol and triglyceride as dependent variables, fasting insulin concentration but not BMI, WHR, or maximal oxygen uptake (VO2max), a measure of physical fitness, predicted HDL cholesterol (R2 = 0.07, p less than 0.02) and triglyceride (R2 = 0.20, p less than 0.001) concentrations. The data suggest that plasma insulin concentration is an important predictor of HDL cholesterol and triglyceride concentrations independent of BMI, WHR, or VO2max.

Aged↗

PubMed1980

Effects of increases in plasma vasopressin concentration on plasma renin activity, blood pressure, heart rate, and plasma corticosteroid concentration in conscious dogs.

It is known that vasopressin decreases PRA and heart rate and increases blood pressure and plasma corticosteroid concentration. The purpose of this study was to determine the plasma concentration of vasopressin required to produce these effects. Arginine vasopressin was administered iv to five normal conscious dogs as priming injections of 0.1, 0.5, 1.0, 2.5, 5.0, and 10.0 ng/kg, followed by infusions of 0.01, 0.05, 0.1, 0.25, 0.5, and 1.0 ng/kg x min, respectively, for 30 min. These doses produced increases in the plasma vasopressin concentration (+/- SE) of 1.0 +/- 0.8, 2.1 +/- 4.3, 4.3 +/- 1.8, 11.4 +/- 1.0, 19.7 +/- 6.4, and 30.8 +/- 7.8 pg/ml, respectively, from a basal level of 2.7 +/- 0.2 pg/ml. An increase in the plasma vasopressin concentration of 2.1 +/- 0.3 pg/ml suppressed PRA by 19 +/- 5% (P < 0.02); increases of 4.2 +/- 1.8 pg/ml or more suppressed PRA by 34 +/- 12% (P < 0.005). Only the highest dose of vasopressin produced a significant pressor effect (9 +/- 3 mm Hg; P < 0.05) or lowered the heart rate (18 +/- 4 beats/min; P < 0.005). An increase in plasma vasopressin concentration of 19.7 +/- 6.4 pg/ml was required to increase the plasma corticosteroid concentration (1.2 +/- 0.2 to 2.2 +/- 0.4 microgram/dl; P < 0.01); the largest dose of vasopressin increased the plasma corticosteroid concentration from 1.5 +/- 0.1 to 2.4 +/- 0.6 microgram/dl (P < 0.02). Twenty-four-hour water deprivation in the same dogs increased the plasma vasopressin concentration from 2.5 +/- 0.2 to 7.4 +/- 0.6 pg/ml (P < 0.01). Nonhypotensive hemorrhage in another group of dogs increased the plasma vasopressin concentration from 2.5 +/- 0.2 to 47.4 +/- 16.8 pg/ml (P < 0.05). These data indicate that elevations in the plasma vasopressin concentration within the range observed during 24 h of water deprivation and nonhypotensive hemorrhage produced significant decreases in renin secretion and heart rate and elevations in blood pressure and corticosteroid secretion.

Adrenal Cortex Hormones↗

PubMed2006

Changes of fructose concentrations in seminal plasma and glucose and testosterone concentrations in blood plasma in rams over the course of a year.

The present study was performed to examine seasonal changes in the fructose concentrations of seminal plasma and glucose and testosterone concentrations of blood plasma over the course of a year (from November 2004 to November 2005) using 5 Suffolk rams. Osmolality of the seminal plasma was also measured. The fructose concentrations in the seminal plasma increased as the breeding season approached, with the maximum in October (179.8 mg/dl) and the minimum in May (6.9 mg/dl), although there were no significant differences during the year. Osmolality of the seminal plasma in February (304 mOsm) was significantly (P<0.05) lower than in January (325 mOsm), July (327 mOsm), and August (325 mOsm). It was also significantly (P<0.05) lower in November (308 mOsm) than in January and August. The blood plasma glucose concentration in October (79.3 mg/dl) was significantly (P<0.05) higher than in January and February (43.2 and 43.7 mg/dl, respectively). The blood plasma testosterone (T) concentrations were significantly (P<0.05) higher in September (8.5 ng/ml) and October (10.2 ng/ml) than in other months. The fructose concentrations in the seminal plasma appeared to be related to the glucose and T concentrations in the blood plasma. These results show that fructose concentrations in the seminal plasma and blood plasma glucose and T concentrations tended to increase during the breeding season, with the highest concentrations in October.

Animals↗

PubMed1979

Serum and urine inorganic fluoride concentrations and urine oxalate concentrations following methoxyflurane anesthesia in the dog.

Plasma fluoride, urine fluoride and urine oxalate concentrations were measured before administering an anesthetic to 8 dogs, and at 0, 3, 9, 24, 48, and 72 hours following 1.5 hours of anesthesia with 1% methoxyflurane. Plasma and urine osmolalities were measured and compared with fluoride and oxalate values. Fluoride concentration increased in both plasma and urine following anesthesia when compared with the preanesthetic concentrations. Maximum mean plasma inorganic fluoride was 106.71 mumoles per liter (+/- 25.44 SE) at 9 hours after exposure to methoxyflurane was completed. By 72 hours after exposure to methoxyflurane the plasma fluoride concentration was 23.47 microM/L (+/- 5.74 SE). Mean urine inorganic fluoride concentration was highest at 9 hours after exposure to methoxyflurane and reached 6047.03 microM/L (+/- 1378.46 SE) as compared to the mean preanesthetic base-line concentration of 542.68 microM/L (+/- 132.93 SE), and the 72 hour mean urine fluoride concentration which was 1593.78 microM/L (+/- 579.46 SE). Urine oxalate concentrations, when compared with urine osmolality (mg/mOsm), increased throughout the study. The 72-hour concentration after exposure to methoxyflurane was 2.5 times the preanesthetic (mg/mOsm) oxalate concentration. Plasma osmolality did not change markedly during the study. Urine osmolalities varied between animals and collection times, but a consistent pattern did not occur. Clinical and laboratory signs of renal dysfunction were not observed in any animal during the study.

Anesthesia↗

PubMed1990

A 23Na-NMR study of sodium-DNA interactions in concentrated DNA solutions at low-supporting electrolyte concentration.

Aqueous solutions of DNA fragments with a contour length (500 A) near the persistence length at DNA concentrations ranging from 10 to 290 mg/mL solvent and a constant supporting electrolyte concentration of 0.01 M (predominantly NaCl) were examined by 23Na-nmr spectroscopy at temperatures of 20, 40, and 60 degrees C. Over the higher portion of this concentration range (greater than 100 mg/ml) the DNA solutions undergo a complex series of transitions between different anisotropic, liquid crystalline phases (T. E. Strzelecka and R. L. Rill, Biopolymers, in press). Counterions in solutions of strong polyelectrolytes are usually described in terms of a two-state model as free or "bound" (influenced by the electrostatic field of the polyanion). The longitudinal relaxation rate (R1 = 1/T1) at all DNA concentrations decreased with increasing temperature, demonstrating fast exchange between free and bound counterions. R1 increased nearly linearly with increasing DNA phosphate/sodium ratio in the isotropic domain until the onset of anisotropic phase formation, in agreement with similar nmr studies conducted at low DNA concentrations. The value of R1,b = 194 +/- 7 Hz obtained for the isotropic phase from 10 to 100 mg DNA/mL at 20 degrees C was in agreement with values reported previously. A nonlinear increase in R1 with DNA concentration was observed upon onset of anisotropic phase formation, indicating an increase in the product of the fraction of bond ions times their relaxation rate (r.R1,b). The spectral lineshape of all isotropic samples was Lorentzian. Spectra of anisotropic samples exhibited low magnitude quadrupole splitting of less than or equal to 400 Hz correlated with appearance of a cholesteric phase with pitch approximately 2 microns. The magnitude of the quadrupole splitting decreased with increasing DNA concentration at low temperatures and increased with concentration at high temperatures. At all concentrations the quadrupole splitting decreased then increased with temperature. These temperature- and concentration-dependent changes in quadrupole splitting are consistent with an angle between the DNA helix axis and the principal component (VZZ) of the local electric field gradient tensor near the "magic angle" of 54.7 degrees.

Animals↗

PubMed1992

Estimation of unbound concentrations of morphine from microdialysate concentrations by use of nonlinear regression analysis in vivo and in vitro during steady state conditions.

The unbound concentration of morphine in striatum of rats was estimated during a constant rate infusion of morphine 14 mumol/h*kg, by use of the microdialysis technique and nonlinear regression analysis. The concentrations in plasma of morphine and its metabolite, morphine-3-glucuronide, were 4.2 +/- 1.4 microM and 7.7 +/- 4.0 microM, respectively, during the constant rate infusion. The corresponding estimated unbound concentrations of morphine in striatum varied between 0.06 and 0.11 microM. No morphine-3-glucuronide was detected in the brain dialysates. The unbound concentration in striatum was lower than expected based on unbound plasma concentrations and could be an indication of active transport from the brain. Five different equations were tested to find the best empirical description of the relationship between microdialysate concentration and perfusion rate by nonlinear regression analysis. The equations were validated by a serum in vitro study, where three unbound concentrations of morphine estimated from microdialyis were compared to estimates obtained from equilibrium dialysis. The precision of the parameter estimates obtained from the five equations was tested by Monte Carlo simulations. One of the equations (Eq. 4) was selected in preference to the others, because of the good agreement with the estimated unbound concentration obtained by equilibrium dialysis in vitro, and good precision of the parameter estimates. The method described in this paper is valuable when estimating the unbound concentration of drug from microdialysate concentrations during steady state conditions. Furthermore, the method is easily accessible when working in the pharmacokinetic and pharmacodynamic field.

Animals↗

PubMed1995

Determination of the concentration of influenza virus antihaemagglutinin antibody molecules of the IgG class and of the equilibrium constant by use of enzyme immunoassay titres determined for graded epitope concentrations.

A new technique for determining the concentration of influenza virus antihaemagglutinin antibody molecules of the IgG class (A) and of the equilibrium constant K of paratope-epitope interaction is described. The method is based on determining enzyme immunoassay (EIA) titres of antibody with graded epitope concentrations: EIA titres were defined in terms of the antibody dilution yielding a fixed amount of antibody adsorbed per ml (= 6.21 x 10(10)). Adsorption of antibody depends on the concentration of paratopes and epitopes allowed to react and on the equilibrium constant. For the use of a constant concentration of epitopes, the paratope concentration needed to yield the desired degree of antibody adsorption decreases with increasing avidity. Therefore, the EIA titres increase both with increasing avidity and increasing antibody concentration. When graded epitope concentrations are used for determining the EIA titres of a given serum, the titres are influenced in a similar manner by the antibody concentration of the serum and the increase of titres with increasing epitope concentration reflects avidity. The equilibrium constant found is subsequently used to determine the concentration of free antibody at the dilution meeting the definition of EIA titre and the product of EIA titre and the sum of free and bound antibody at this dilution gives the number of antibody molecules present in the test serum. A panel of 118 antisera was tested comparatively for A and K using the new method and by means of the guanidine titre ratio test and equilibrium filtration. The values obtained agreed well with each other. This novel technique offers the advantage that it can be easily adapted for use with other viruses.

Animals↗