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PubMed1999

Serum total homocysteine concentrations in the third National Health and Nutrition Examination Survey (1991-1994): population reference ranges and contribution of vitamin status to high serum concentrations.

BACKGROUND: The concentration of circulating total homocysteine is a sensitive marker of inadequate folate and vitamin B12 status. Elevated homocysteine concentrations are associated with an increased risk for vascular disease. OBJECTIVE: To identify reference ranges for serum total homocysteine concentration in U.S. residents and quantify the contribution of circulating vitamin concentrations to high homocysteine concentrations. DESIGN: Cross-sectional prevalence study. SETTING: United States. PATIENTS: A nationally representative sample of 3563 male participants and 4523 female participants 12 years of age or older who participated in the third National Health and Nutrition Examination Survey. MEASUREMENTS: Reference ranges (5th and 95th percentiles) for the total homocysteine concentration were defined among participants who were folate- and vitamin B12-replete and had normal creatinine concentrations. A high total homocysteine concentration was defined as one that exceeded the sex-specific 95th percentile for the reference sample (participants 20 to 39 years of age). The population attributable risk percentage was calculated to determine the contribution of low folate (<11 nmol/L) and vitamin B12 (<185 pmol/L) concentrations to a high homocysteine concentration. RESULTS: Reference ranges for serum total homocysteine concentration increased with age; these ranges were 4.3 to 9.9 micromol/L for male participants and 3.3 to 7.2 micromol/L for female participants 12 to 19 years of age and from 5.9 to 15.3 micromol/L for men and 4.9 to 11.6 micromol/L for women 60 years of age or older. A high homocysteine concentration was defined as at least 11.4 micromol/L for male participants and at least 10.4 micromol/L for female participants. Approximately two thirds of the cases of high homocysteine concentrations were associated with low vitamin concentrations. CONCLUSIONS: Upper reference limits for the serum total homocysteine concentration increased with age and were higher for male participants than for female participants at all ages. In most cases, high homocysteine concentrations were associated with low serum vitamin concentrations.

Adolescent↗

PubMed2000

Relationship between arterial, mixed venous, and internal jugular carboxyhemoglobin concentrations at low, medium, and high concentrations in a piglet model of carbon monoxide toxicity.

OBJECTIVE: This study tested the hypothesis that mixed venous carboxyhemoglobin concentrations (V-COHb) and internal jugular carboxyhemoglobin concentrations (I-COHb) accurately predict arterial carboxyhemoglobin concentrations (A-COHb). In addition, this study tested the hypothesis that there is a high correlation at low (COHb, 0% to 10%), moderate (COHb, >10% to 40%), and high (COHb, >40%) concentrations between V-COHb, I-COHb, and A-COHb. DESIGN: The study was a prospective comparison of A-COHb, V-COHb, and I-COHb concentrations in piglets exposed to increasing concentrations of carbon monoxide over 6 hrs to achieve a concentration of > or =60% COHb. Carboxyhemoglobin measurements were evaluated by analysis of variance and correlation analysis. Agreement between V-COHb and A-COHb concentrations was examined by using a plot of arteriovenous differences against the mean of the two measurements. INTERVENTION: We simultaneously sampled arterial, mixed venous, and internal jugular blood every 30 mins over the 6-hr study period. RESULTS: Two hundred fifty arterial and mixed venous COHb concentrations were obtained, and 214 internal jugular COHb concentrations were obtained. One hundred additional arterial, mixed venous, internal jugular, and peripheral COHb concentrations were obtained. Correlation between samples at each concentration revealed r2 > = .94. CONCLUSION: Venous COHb concentrations predict arterial COHb concentrations with a high degree of accuracy and are correlated at low, moderate, and high concentrations of carbon monoxide exposure. Arterial or venous samples can be used to accurately measure COHb concentrations.

Animals↗

PubMed1979

Testosterone and estradiol concentrations in paired maternal and cord sera and their correlation with the concentration of chorionic gonadotropin.

Testosterone (T) and estradiol (E2) concentrations were determined and correlated with beta human chorionic gonadotropin (beta-HCG) concentrations in 43 paired maternal and cord sera (22 female and 21 male infants). Mean (+/- SD) maternal E2 concentrations were significantly (P less than .005) higher when the sex of the fetus was male than when the sex of the fetus was female (20.6 +/- 3.9 vs 13.5 +/- 3.2 ng/ml). Maternal T concentrations were not significantly different when related to the sex of the fetus (males, 114.8 +/- 60.7 vs females, 113.8 +/- 54.5 ng/100 ml, P greater than .1). Regression analysis did not show a significant correlation between maternal T or E2 concentrations and maternal beta-HCG concentrations. Mean cord serum T and E2 concentrations of male infants were significantly greater than that of female infants (T, 38.8 +/- 8.5 vs 25.8 +/- 7.1 ng/100 ml, P less than .005; E2, 9.1 +/- 3.3 vs 6.6 +/- 2.0 ng/ml, P less than .005). Regression analysis showed a significant (P less than .005) correlation between cord beta-HCG concentrations and E2 concentrations for male infants (r = .7) and female infants (r = .6). A significant correlation between cord beta-HCG concentrations and T concentrations was found for male infants (r = .5; P less than .01) but not for female infants (r = .3; P greater than .05). There was no correlation between maternal and infant E2 concentrations (males, r = .3, P greater than .05; females, r = .3, P greater than .2) or T concentrations (males, r = .02, P greater than 0.4; females, r = .06, P greater than .3). These data (1) confirm the sex difference in cord serum T and E2 concentrations, (2) indicate that the lower beta-HCG concentrations in mothers of male infants are associated with E2 concentrations which are greater than those in mothers of female infants, and (3) are consistent with an influence of beta-HCG on fetal T and E2 secretion.

Chorionic Gonadotropin↗

PubMedDate not supplied

[Blood urea concentration, a parameter for the assessment of protein metabolism in pregnant sows. 2. Relations between blood urea concentration and urine nitrogen excretion as well as estimation of urine nitrogen excretion from the blood urea concentration].

The influence of supplementing the ration with the limiting amino acid lysine on N-excretion in urine and the urea concentration in the blood (UCB) is investigated in an experiment with pregnant young sows. In contrast or the basic ration the most satisfactory N-utilisation reflects itself after a lysine intake of 8.2 g/animal and day during the early phase of gestation and 8.6 g during the last phase of gestation both in a diminished N-excretion in urine and a lower UCB. The following correlation coefficients were calculated for the relation between UCB an N-excretion in urine: early phase of gestation: 0.177 (n = 37); last phase of gestation. 0.431 (n = 30); gestation as a whole: 0.416 (n = 67). In a second experiment methionine supplementation in the feeding of a ration with a deficit of sulphur-containing amino acids led to a significant decrease of N-excretion in urine (alpha = 5%). While UCB also significantly decreased 5 hours after feeding, UCB virtually did not react to a changed level of amino acid intake when the blood sample was taken before feeding. In a third experiment, in which 49 g N/animal and day were taken in, differences regarding N-excretion in urine and UCB between pregnant and non-pregnant animals could not be established. When the results published in the first communication (Herrmann and Schneider, 1981) are included, the following correlation coefficients for the relation between N-excretion in urine and UCB are the result: 0.716 (n = 182) for sampling before feeding and 0.808 (n = 133) for sampling 5 hours after feeding. The confidence range of the estimated function y = -2.97 + 1.233 chi for the relation between N-excretion in urine (y; g/animal and day) and UCB 5 hours after feeding (chi; mg/100 ml serum) as well as the variability values do not make it possible to estimate N-excretion in urine from UCB with satisfactory accuracy.

Animals↗

PubMed1976

[The "anomalous" relationship between the concentration of potassium in the medium and the membrane potential of muscle fibers with a decreased intracellular potassium concentration. II. Rate of forward and reverse K42 transport through muscle fiber membranes in saccharose-sulfate solutions with potassium concentrations of 2.5 and 75 mM].

The measurements were made of the unidirectional potassium fluxes, the rate constants and the permeability coefficient. At external potassium 2.5 mM, the outflux and influx are 10--15, and 22-29 micromol/h g d. wt, respectively, and the net flux is comparable with the unidirectional fluxes. At external potassium 75 mM, the unidirectional fluxes increase up to 70--80 micromol/h, g d. wt. and the net flux does not exceed 0.1 of the unidirectional one. The outflux rate constant/influx rate constant ratio for both the potassium concentrations is about 1.5 times below the Ussing's ratio. This effect cannot be accounted for the single file phenomenon since it is independent of the direction and value of the net potassium flux. The discrepancy between the measured membrane potential and EK may, to some extent, be due to peculiarities of potassium movement.

Animals↗

PubMed2003

Does lead interfere with hemoglobin-based oxygen carrier (HBOC) function? A pilot study of lead concentrations in three approved or tested HBOCs and oxyhemoglobin dissociation with HBOCs and/or bovine blood with varying lead concentrations.

UNLABELLED: We measured lead concentrations in three hemoglobin-based oxygen carriers (HBOCs; Oxyglobin, Hemopure, and Hemolink) and compared them with lead concentrations from blood-bank blood. Oxyhemoglobin dissociation was measured with large concentrations of lead in bovine HBOC, with or without bovine blood, and in bovine blood. Samples of each were prepared by combining one with normal saline (control), the second with small lead concentrations (22 micro g/dL), and the third with toxic lead concentrations (70 micro g/dL). They were blended in 2 tonometers at oxygen concentrations (2.5%, 5%, 8%, 10%, 21%, and 95%) with 5% CO(2) and the remainder nitrogen for 5 min per sample after a 15-min wash-in with each level of oxygen and were measured with co-oximetry. Oxygen saturation was plotted against PO(2), fitting fourth-order polynomial nonlinear regression to the data. The lead concentrations of the three HBOCs were 0.51, 0.22, 0.40 micro g/dL. There were no clinically important differences of the oxyhemoglobin dissociation curves as a function of lead concentration. The lead concentrations of the three tested HBOCs were small and no larger than the average for blood-bank blood. The presence of increasing concentrations of lead in either concentrated solution of bovine HBOC or a 1:1 mixture of bovine HBOC and native bovine blood does not appear to affect hemoglobin oxygenation in an acute in vitro model of increased lead concentrations. IMPLICATIONS: Gunshot wounds rapidly increase circulating lead concentrations. Lead concentrations are small in three hemoglobin-based oxygen carriers (HBOCs), and HBOCs and/or bovine blood do not appear to be affected by lead concentrations in terms of immediate oxygen on-loading and off-loading. HBOCs may be useful in patients with gunshot wounds.

Animals↗

PubMed2004

Effects of crude protein concentration and degradability on performance, carcass characteristics, and serum urea nitrogen concentrations in finishing beef steers.

Two experiments were conducted at two locations to determine the effects of dietary CP concentration and source on performance, carcass characteristics, and serum urea nitrogen (SUN) concentrations of finishing beef steers. British x Continental steers were blocked by BW (357 +/- 28 and 305 +/- 25 kg initial BW; n = 360 and 225; four and five pens per treatment in Exp. 1 and 2, respectively). Steam-flaked corn-based diets were arranged in a 3 x 3 factorial with three CP concentrations (11.5, 13, or 14.5% of DM) and three sources of supplemental CP (N basis): 100% urea; 50:50 blend of urea and cottonseed meal; or 100% cottonseed meal. Steers in both experiments were initially implanted with Ralgro and reimplanted with Revalor-S on d 56. Performance and carcass data were pooled across locations. Crude protein concentration x source interactions were not observed (P = 0.22 to 0.93) for performance and carcass data. Crude protein concentration affected ADG (P = 0.02) and carcass-adjusted (to a common dressing percent within location) ADG quadratically (P = 0.06). Increasing the concentration of supplemental urea linearly increased carcass-adjusted ADG and G:F (P < 0.05) and carcass-adjusted G:F (P < 0.001). Dry matter intake was not affected (P = 0.93) by either CP concentration or source. Hot carcass weight (HCW; P = 0.02), LM area (P = 0.05), and dressing percent (P = 0.03) increased linearly with increasing urea concentration, whereas increasing CP concentration quadratically affected HCW (P = 0.02), with a maximum at 13% CP. Differences in backfat thickness and yield grade were negligible across treatments. Neither marbling score nor percentage of carcasses grading USDA Choice was affected by CP concentration or source. At all times measured, SUN concentrations increased (P < 0.05) with increasing CP concentration, but effects of CP source were small and variable across time. Results indicate that increasing CP concentrations from 11.5 to 13% slightly increased ADG and carcass-adjusted ADG, whereas increasing the proportion of supplemental urea increased carcass-adjusted ADG, G:F, and carcass-adjusted G:F and increased HCW, LM area, and dressing percent. A CP concentration above 13% seemed detrimental to ADG and HCW. Serum urea N increased over time, with CP concentration having a greater effect than CP source.

Animal Feed↗

PubMed1992

Variations in tumor cell growth rates and metabolism with oxygen concentration, glucose concentration, and extracellular pH.

Tumors and multicellular tumor spheroids can develop gradients in oxygen concentration, glucose concentration, and extracellular pH as they grow. In order to calculate these gradients and assess their impact on tumor growth, it is necessary to quantify the effect of these variables on tumor cell metabolism and growth. In this work, the oxygen consumption rates, glucose consumption rates, and growth rates of EMT6/Ro mouse mammary tumor cells were measured at a variety of oxygen concentrations, glucose concentrations, and extracellular pH levels. At an extracellular pH of 7.25, the oxygen consumption rate of EMT6/Ro cells increased by nearly a factor of 2 as the glucose concentration was decreased from 5.5 mM to 0.4 mM. This effect of glucose concentration on oxygen consumption rate, however, was slight at an extracellular pH of 6.95 and disappeared completely at an extracellular pH of 6.60. The glucose consumption rate of EMT6/Ro cells increased by roughly 40% when the oxygen concentration was reduced from 0.21 mM to 0.023 mM and decreased by roughly 60% when the extracellular pH was decreased from 7.25 to 6.95. The growth rate of EMT6/Ro cells decreased with decreasing oxygen concentration and extracellular pH; however, severe conditions were required to stop cell growth (0.0082 mM oxygen and an extracellular pH of 6.60). Empirical correlations were developed from these data to express EMT6/Ro cell growth rates, oxygen consumption rates, and glucose consumption rates, as functions of oxygen concentration, glucose concentration, and extracellular pH. These empirical correlations make it possible to mathematically model the gradients in oxygen concentration, glucose concentration, and extracellular pH in EMT6/Ro multicellular spheroids by solution of the diffusion/reaction equations. Computations such as these, along with oxygen and pH microelectrode measurements in EMT6/Ro multicellular spheroids, indicated that nutrient concentration and pH levels in the inner regions of spheroids were low enough to cause significant changes in nutrient consumption rates and cell growth rates. However, pH and oxygen concentrations measured or calculated in EMT6/Ro spheroids where quiescent cells have been observed were not low enough to cause the cessation of cell growth, indicating that the observed quiescence must have been due to factors other than acidic pH, oxygen depletion, or glucose depletion.

Animals↗

PubMed1999

Effects of tylosin on concentrations of Fusobacterium necrophorum and fermentation products in the rumen of cattle fed a high-concentrate diet.

OBJECTIVE: To determine effects of tylosin on ruminal concentrations of Fusobacterium necrophorum and fermentation products in cattle during rapid adaptation to a high-concentrate diet. ANIMALS: 6 steers fitted with ruminal cannulas. PROCEDURE: Steers were assigned randomly to 2 treatment groups and switched from a 0 to an 85% concentrate diet during a 4-day period. Cattle received this diet, with or without tylosin (90 mg/steer/d), for 4 weeks. Samples of ruminal contents were collected daily beginning 2 days before the treatment protocol and in the first week of concentrate feeding. Four subsequent samples were collected at weekly intervals. Concentration of F. necrophorum in samples was determined, using the most-probable-number technique. Ruminal pH and concentrations of volatile fatty acids (VFA), lactate, and ammonia also were determined. All steers received both treatments separated by 4 weeks (cross-over design), during which time they were fed alfalfa hay only. RESULTS: In control steers, concentration of F. necrophorum increased in response to the high-concentrate diet. Tylosin-fed steers had lower concentrations of F. necrophorum than control steers at all times during concentrate feeding. However, ruminal pH and concentrations of lactate, VFA, and ammonia did not differ between treatment groups. CONCLUSIONS AND CLINICAL RELEVANCE: Tylosin caused a significant reduction in ruminal concentrations of F. necrophorum during rapid adaptation to a high-concentrate diet but had no effect on fermentation products. The reduction in ruminal concentration of F. necrophorum helps explain the reduction in prevalence of hepatic abscesses reported in tylosin-fed feedlot cattle.

Ammonia↗

PubMed2005

Estimating the fasting triglyceride concentration from the postprandial HDL-cholesterol and apolipoprotein CIII concentrations.

Hypertriglyceridemia is an important risk factor for atherosclerosis. In the fasting state, the triglyceride (TG) concentration is correlated significantly with the high-density lipoprotein-cholesterol (HDL-C) and apolipoprotein CIII (apoCIII) concentrations. A postprandial change is evident in TG, but negligible in HDL-C and apoCIII. We investigated whether the fasting TG concentration could be estimated from the postprandial HDL-C and apoCIII concentrations. We measured the TG, HDL-C, and apoCIII concentrations at seven points a day in 58 inpatients. Multiple regression analysis showed that the actual fasting TG concentration was strongly correlated with the TG concentration estimated from the fasting HDL-C and apoCIII concentrations (ln[TG](fasting)=0.0140[apoCIII](fasting)-0.724[HDL-C](fasting)-0.142, r=0.852, p<0.001). This equation was also fit to the fasting data from 163 outpatients (r=0.883, p<0.001). Although the TG concentration increased by up to 28.2%, the HDL-C and apoCIII concentrations changed little during the day. When we substituted the postprandial HDL-C and apoCIII concentrations for the respective fasting values in this equation, there were still strong positive correlations (r=0.794-0.840) between the actual and estimated fasting TG concentrations throughout the day. In conclusion, the fasting TG concentration can be estimated from the postprandial HDL-C and apoCIII concentrations.

Aged↗

PubMed2005

Feeding-dependent depression of melanin-concentrating hormone and melanin-concentrating hormone receptor-1 expression in vagal afferent neurones.

Food intake is regulated by signals from the gastrointestinal tract. Both stimulation and inhibition of food intake may be mediated by upper gastrointestinal tract hormones, e.g. ghrelin and cholecystokinin that act at least partly via vagal afferent neurones. We now report that vagal afferent neurones in both rat and man express melanin-concentrating hormone and its receptor, melanin-concentrating hormone-1R. In nodose ganglia from rats fasted for 24 h, RT-PCR revealed the expression of both melanin-concentrating hormone and melanin-concentrating hormone-1R, whereas in ganglia from animals fed ad libitum expression was virtually undetectable. Immunohistochemical studies also revealed expression of melanin-concentrating hormone and melanin-concentrating hormone-1R in nodose ganglion neurones of fasted rats, but signals were weak in rats fed ad libitum. Melanin-concentrating hormone and melanin-concentrating hormone-1R were expressed in the same neurones, a high proportion of which also expressed the cholecystokinin-1 receptor. When fasted rats were refed, there was down-regulation of melanin-concentrating hormone and melanin-concentrating hormone-1R expression over a period of 5 h. Similar effects were produced by administration of cholecystokinin to fasted rats. The cholecystokinin-1 receptor antagonist lorglumide inhibited food-induced down-regulation of melanin-concentrating hormone and melanin-concentrating hormone-1R. We conclude that the satiety hormone cholecystokinin acts on vagal afferent neurones to inhibit expression of melanin-concentrating hormone and its receptor. Since the melanin-concentrating hormone system is associated with stimulation of food intake this effect of cholecystokinin may contribute to its action as a satiety hormone.

Afferent Pathways↗

PubMedDate not supplied

The effect of increased concentrations of homocysteine on the concentration of (E)-4-hydroxy-2-nonenal in the plasma and cerebrospinal fluid of patients with Alzheimer's disease.

There is evidence that increased blood concentrations of homocysteine may be a risk factor for Alzheimer's disease. (E)-4-hydroxy-2-nonenal (HNE) is a neurotoxic product of lipid peroxidation that is increased in the ventricular fluid and brains of patients with Alzheimer's disease. We measured the concentrations of homocysteine, HNE, vitamin B(12) and folate in the plasma of 27 patients with Alzheimer's disease and 25 control subjects. There was a statistically significant increase in the plasma concentration of homocysteine (P < 0.001) and HNE (P < 0.001) in the Alzheimer's disease patients compared to the control group. There was a significant decrease in the plasma concentration of vitamin B(12) (P < 0.001) and folate (P = 0.002) in the Alzheimer's group compared to the controls. There was a significant positive correlation between the plasma concentrations of homocysteine and HNE in the patients with Alzheimer's disease (r = 0.661, P < 0.001). A significant negative correlation was found between the plasma concentration of homocysteine and the plasma concentrations of vitamin B(12) (r = -0.605, P = 0.0006) and folate (r = 0.586, P = 0.001). We also measured the concentrations of homocysteine, HNE, vitamin B(12) and folate in the cerebrospinal fluid (CSF) of 8 patients with Alzheimer's disease compared to 6 control subjects. The concentrations of homocysteine (P = 0.032) and HNE (P = 0.001) were significantly higher in the CSF of Alzheimer's patients than in the control subjects. There were significant positive correlations between the CSF concentrations of homocysteine and HNE (r = 0.924, P = 0.001). There was also a significant positive correlation between the plasma concentration of homocysteine and the CSF concentrations of homocysteine (r = 0.850, P = 0.007) and HNE (r = 0.092, P = 0.002). These results demonstrate that there is a relationship between increased homocysteine concentrations and increased HNE concentrations in Alzheimer's disease.

Aged↗

PubMed1997

Correspondence of salivary and plasma concentrations of atrazine in rats under variable salivary flow rate and plasma concentration.

The stability of the saliva/plasma (S/P) concentration ratio of atrazine was determined under varying conditions of salivary flow rate and plasma concentration of atrazine in Sprague-Dawley rats. In the salivary flow study, whole saliva samples were collected at different salivary flow rates while the plasma concentration of atrazine was maintained at a steady-state level of approximately 150 micrograms/L. In the plasma level study, whole saliva samples were collected at two steady-state plasma concentrations of atrazine (50 and 250 micrograms/L), while salivary flow rate was maintained at a relatively constant level. In both studies, atrazine concentrations in whole saliva and arterial plasma demonstrated a consistent relationship, but salivary concentrations were always lower than those of arterial plasma. Linear regression analysis demonstrated that the S/P concentration ratio of atrazine was not significantly different for salivary flow rates ranging from 23 to 92 microL/min/kg body weight, and did not vary for atrazine plasma concentrations between 30 and 433 micrograms/L. The S/P concentration ratio of atrazine was relatively constant throughout each experimental period (0.68 +/- 0.1 and 0.70 +/- 0.11 for salivary flow and plasma level studies, respectively) and did not differ significantly between rats. When data from both studies were pooled, salivary concentrations were highly correlated with plasma concentrations (r2 = .94). It is concluded that under these experimental conditions, the stability of the S/P concentration ratio of atrazine is not affected by variations in salivary flow rate or atrazine plasma concentrations. The results from this study support the conclusion that atrazine salivary concentrations can be used to predict plasma levels of atrazine in rats.

Analysis of Variance↗

PubMedDate not supplied

Starch concentration and impact on specific leaf weight and element concentrations in potato leaves under varied carbon dioxide and temperature.

Foliar concentrations of starch and major elements, nitrogen (N), phosphorus (P), potassium (K), calcium (Ca), and magnesium (Mg), along with specific leaf weight (SLW) were determined in the potato (Solanum tuberosum L.) cvs 'Denali', 'Norland', and 'Russet Burbank' grown for 35 days under CO2 concentrations of 500, 1,000, 1,500 and 2,000 micromoles mol-1 at both 16 degrees C and 20 degrees C air temperature. The starch concentration, pooled from the three cultivars, increased with increasing CO2 concentration at both 16 degrees C and 20 degrees C and was consistently higher at 16 degrees C than at 20 degrees C. The SLW (g m-2) was positively related to the foliar starch concentration on the basis of leaf area or dry weight. The concentrations of N, P, Ca, and Mg in leaves were negatively related to starch concentration under approximately 14% starch on a dry weight basis. Above 14% starch, there was no significant relationship between element and starch concentrations. Similar patterns were seen when the SLW and element concentrations were expressed on a starch-free basis. In contrast, the leaf concentration of K was not closely related to the starch concentration because the K concentration was similar at varied CO2 levels. The results of this study indicate that the changes in SLW and concentrations of N, P, Ca, and Mg in potato leaves only partially resulted from the changed starch concentration.

Biomass↗

PubMed1989

Unbound phenytoin plasma concentrations in patients comedicated with sodium valproate--the predictive value of plasma albumin concentration.

1. Phenytoin protein binding in epileptic patients on phenytoin as monotherapy has been compared with protein binding in patients treated with both phenytoin and sodium valproate. In addition the relative value of assayed total phenytoin plasma concentrations and assayed unbound phenytoin plasma concentrations and the value of predicted unbound phenytoin plasma concentrations in predicting phenytoin toxicity has been assessed. 2. The mean phenytoin unbound fraction for patients taking sodium valproate (0.122) was significantly greater than for those on monotherapy (0.082). 3. There were six episodes of clinical toxicity. In five toxic episodes the assayed unbound phenytoin plasma concentration was a better reflection of toxicity than the assayed total phenytoin plasma concentration, and four of these occurred in patients on sodium valproate. 4. Unbound phenytoin plasma concentrations were predicted from a single regression equation correlating all assayed total phenytoin plasma concentrations with assayed unbound phenytoin plasma concentrations, from two separate regression equations for each group of patients, and from the correlation between phenytoin protein binding and plasma albumin concentration. 5. The unbound phenytoin plasma concentrations predicted from the two regression equations were statistically no less effective than the assayed unbound phenytoin plasma concentrations in assessing toxicity. 6. Despite a correlation between plasma albumin concentrations and phenytoin protein binding, the use of albumin concentrations in predicting unbound phenytoin plasma concentrations appeared to be of little additional benefit.

Adult↗

PubMed2005

Pharmacokinetic/pharmacodynamic modelling of antibacterials in vitro and in vivo using bacterial growth and kill kinetics: the minimum inhibitory concentration versus stationary concentration.

BACKGROUND: The minimum inhibitory concentration (MIC) is the in vitro reference value to describe the activity of an antibacterial against micro-organisms. It does not represent the dynamic effect of the antimicrobial at any point in time, but rather the total antimicrobial effect over the incubation period at a fixed concentration. OBJECTIVE: To explore the concentration-effect relationship of antimicrobial concentrations against micro-organisms in relation to the MIC. METHODS: Time-kill curves were generated for ceftazidime, meropenem and tobramycin against Pseudomonas aeruginosa. The Hill equation with variable slope was fit to the time-kill data, and mathematical models of growth and kill were explored with reference to the MIC. RESULTS: With declining concentrations, bacterial killing will decrease until a specific threshold concentration is reached. This concentration, at which bacteria are neither killed nor able to grow, is named the stationary concentration (SC) and is not equal to the MIC. Pharmacokinetic/pharmacodynamic simulations over a range of kill rates, growth rates and slope factors showed that for beta-lactam antibacterials, the SC is close to the MIC value, which may explain why concentrations in vivo need to be above the MIC, while regrowth of bacteria occurs when concentrations decline below the MIC. For concentration-dependent antibacterials, such as aminoglycosides and quinolones, the SC is shown to be markedly different from the MIC and, in general, is much lower. CONCLUSION: The MIC is not a good pharmacodynamic parameter to characterise the concentration effect relationship of a given antimicrobial. For 'concentration independent' antimicrobials the SC is likely to be close to the MIC, but may be much lower for 'concentration dependent' antimicrobials, and may explain sub-MIC effects.

Anti-Bacterial Agents↗

PubMed2002

Alpha-tocopherol concentrations and case life of lamb muscle as influenced by concentrate or pasture finishing.

Two experiments were conducted to evaluate alpha-tocopherol accumulation in muscle of lambs finished on pasture or concentrates. The objective for Exp. 1 was to compare accumulation of alpha-tocopherol in the longissimus muscle of pasture-fed lambs to that of lambs fed three concentrations (15, 150, and 300 IU/kg of DM) of supplemental vitamin E (all rac alpha-tocopheryl acetate) in all-concentrate diets. The objective in Exp. 2 was to investigate the effect of duration of supplemental vitamin E feeding on alpha-tocopherol content and color change during display case storage of lamb muscle. Treatments evaluated in Exp. 2 were: 15 IU of supplemental vitamin E/kg DM fed to finish; 15 IU/kg followed by 300 IU/kg of DM during the last 21 d; and 15 IU/kg DM until 7 d prior to finish, then 300 IU/kg DM. In Exp. 1, alpha-tocopherol concentration of rotational grazed alfalfa and perennial ryegrass averaged 137 and 169 mg/kg of DM. Vitamin E treatments for lambs fed concentrate diets did not affect ADG (P > 0.15), but ADG was greater (P < 0.01) for concentrate-fed lambs than for grazing lambs. For the concentrate-fed lambs, alpha-tocopherol in longissimus muscle increased quadratically (P < 0.05) as dietary concentrations of vitamin E increased. Predicted maximum alpha-tocopherol concentration in muscle occurred at about 400 IU/kg of diet DM. Longissimus muscle from lambs grazing alfalfa or ryegrass had similar (P > 0.50) alpha-tocopherol concentrations, and those concentrations were similar to values obtained when the concentrate diet supplemented with 150 IU of vitamin E/kg was fed. In Exp. 2, no differences (P > 0.10) in ADG were observed. Concentrations of longissimus alpha-tocopherol were highest when 300 IU supplemental vitamin E was fed for 21 d prior to slaughter. During a 6-d display period, semimembranosus steaks from lambs fed 300 IU of supplemental vitamin E/kg for either 7 or 21 d had higher a* and b* color readings than steaks from lambs fed 15 IU/kg of supplemental vitamin E. Increased consumption of vitamin E either via pasture or supplementation results in higher alpha-tocopherol concentrations in meat.

Animal Feed↗

PubMed2003

Metallothionein concentrations in natural populations of gudgeon (Gobio gobio): relationship with metal concentrations in tissues and environment.

A field monitoring campaign investigating the suitability of (Cd, Zn)-metallothionein concentrations (MTs) in different tissues of the gudgeon as a biomarker for metal contamination in the aquatic environment was conducted. Gudgeons were captured at 10 sampling sites on a river system in Flanders (Belgium). Nine sampling sites were situated along a Cd and Zn gradient with a nearby tributary as the reference site. Cadmium, Cu, and Zn concentrations were measured in the water and sediments. Concentrations of (Cd, Zn)-MT were measured in different organs (gill, liver, kidney) of gudgeon (Gobio gobio). The hepatic and gill Cd and Zn concentrations, as well as the hepatic (Cd, Zn)-MT concentrations, reflected the polymetallic contamination gradient. Moreover, the hepatic Cd and Zn concentrations could describe 72% of the variance in the (Cd, Zn)-MT concentrations in the liver, illustrating the possible use of hepatic MT concentrations as a biomarker for environmental metal contamination. In this way a dose-response relationship could be established under natural conditions. However, a poor negative relation between the Cd and Zn concentrations in the gills and the corresponding (Cd, Zn)-MT concentrations was found. No relation between the Cd and Zn concentrations in the kidney tissue and the corresponding (Cd, Zn)-MT concentrations could be established. These results clearly illustrate the tissue-specificity of the MT concentrations, thus for monitoring purposes MT concentrations should be measured in liver tissues, rather than in kidney or gill tissues.

Animals↗