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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Risk analysis 19 (1999), S. 711-726 
    ISSN: 1539-6924
    Keywords: variability ; exposure ; susceptibility ; risk assessment ; pharmacokinetics ; pharmacodynamics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Energy, Environment Protection, Nuclear Power Engineering
    Notes: Abstract This paper reviews existing data on the variability in parameters relevant for health risk analyses. We cover both exposure-related parameters and parameters related to individual susceptibility to toxicity. The toxicity/susceptibility data base under construction is part of a longer term research effort to lay the groundwork for quantitative distributional analyses of non-cancer toxic risks. These data are broken down into a variety of parameter types that encompass different portions of the pathway from external exposure to the production of biological responses. The discrete steps in this pathway, as we now conceive them, are: •Contact Rate (Breathing rates per body weight; fish consumption per body weight) •Uptake or Absorption as a Fraction of Intake or Contact Rate •General Systemic Availability Net of First Pass Elimination and Dilution via Distribution Volume (e.g., initial blood concentration per mg/kg of uptake) •Systemic Elimination (half life or clearance) •Active Site Concentration per Systemic Blood or Plasma Concentration •Physiological Parameter Change per Active Site Concentration (expressed as the dose required to make a given percentage change in different people, or the dose required to achieve some proportion of an individual's maximum response to the drug or toxicant) •Functional Reserve Capacity–Change in Baseline Physiological Parameter Needed to Produce a Biological Response or Pass a Criterion of Abnormal Function Comparison of the amounts of variability observed for the different parameter types suggests that appreciable variability is associated with the final step in the process–differences among people in “functional reserve capacity.” This has the implication that relevant information for estimating effective toxic susceptibility distributions may be gleaned by direct studies of the population distributions of key physiological parameters in people that are not exposed to the environmental and occupational toxicants that are thought to perturb those parameters. This is illustrated with some recent observations of the population distributions of Low Density Lipoprotein Cholesterol from the second and third National Health and Nutrition Examination Surveys.
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  • 2
    ISSN: 1539-6924
    Keywords: MeHg ; pharmacokinetics ; PBPK model ; variability ; risk assessment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Energy, Environment Protection, Nuclear Power Engineering
    Notes: Abstract An analysis of the uncertainty in guidelines for the ingestion of methylmercury (MeHg) due to human pharmacokinetic variability was conducted using a physiologically based pharmacokinetic (PBPK) model that describes MeHg kinetics in the pregnant human and fetus. Two alternative derivations of an ingestion guideline for MeHg were considered: the U.S. Environmental Protection Agency reference dose (RfD) of 0.1 μg/kg/day derived from studies of an Iraqi grain poisoning episode, and the Agency for Toxic Substances and Disease Registry chronic oral minimal risk level (MRL) of 0.5 μg/kg/day based on studies of a fish-eating population in the Seychelles Islands. Calculation of an ingestion guideline for MeHg from either of these epidemiological studies requires calculation of a dose conversion factor (DCF) relating a hair mercury concentration to a chronic MeHg ingestion rate. To evaluate the uncertainty in this DCF across the population of U.S. women of child-bearing age, Monte Carlo analyses were performed in which distributions for each of the parameters in the PBPK model were randomly sampled 1000 times. The 1st and 5th percentiles of the resulting distribution of DCFs were a factor of 1.8 and 1.5 below the median, respectively. This estimate of variability is consistent with, but somewhat less than, previous analyses performed with empirical, one-compartment pharmacokinetic models. The use of a consistent factor in both guidelines of 1.5 for pharmacokinetic variability in the DCF, and keeping all other aspects of the derivations unchanged, would result in an RfD of 0.2 μg/kg/day and an MRL of 0.3 μg/kg/day.
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    European journal of nutrition 24 (1985), S. 113-119 
    ISSN: 1436-6215
    Keywords: Chloramphenicol ; pharmacokinetics ; residue ; pig
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Medicine
    Description / Table of Contents: Summary Residues of Chloramphenicol (CAP) were examined in 24 pigs after intramuscular injection of 30 mg CAP/kg body weight. Two pigs were slaughtered after 3, 6, 12,18, 24, 36 hours, 2, 3, 6, 10, 21 and 30 days, respectively. CAP-concentrations were determined in muscle, blood, urine, liver, kidney, bile, and fat. Methods used were gas-liquid chromatography and radioimmunoassay. Detection limits reached were 1−5 ppb. The concentration-time curves obtained reflected a long elimination phase and allowed only calculation of this half-life. Elimination half-life was estimated to be for muscle, blood and urine 160–170 hours, for kidney 310 and for bile 250 hours. Significant correlations were found to exist between CAP-concentrations in plasma and muscle. It appears that blood would be a good body fluid for monitoring CAP-residues in tissue.
    Notes: Zusammenfassung Zur Untersuchung des Rückstandsverhaltens von Chloramphenicol (CAP) wurden 24 Mastschweine, 24–28 Wochen alt, intramuskulär mit 30 mg CAP/kg Körpergewicht behandelt und je 2 Tiere nach 3, 6, 12, 18, 24, 36 Stunden, 2, 3, 6, 10, 21 und 30 Tagen geschlachtet. Die CAP-Gehalte in Muskulatur, Blut, Urin, Leber, Niere, Galle und Fett wurden gaschromatographisch und radioimmunologisch bestimmt. Die Nachweisgrenze beider Methoden liegt in Abhängigkeit von der Matrix zwischen 1 und 5 ppb. Die erhaltenen Kinetiken weisen eine terminale Elimination auf, deren Halbwertszeiten für Muskulatur, Blut und Urin ca. 160–170 Stunden, für Niere 310 Stunden und für Galle 250 Stunden betragen. Die CAP-Konzentration in Muskulatur und Blut weisen eine signifikante, lineare Korrelation auf. Blutuntersuchungen könnten deshalb als Screening-Methode bei umfangreichen Rückstandskontrollen eingesetzt werden.
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  • 4
    ISSN: 1436-6215
    Keywords: purinreiche Nahrung ; Wachstum ; Metaboliten ; Harnsäuretransport ; Hund ; purine-rich diet ; growth ; metabolites ; uric acid transport ; dog
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Medicine
    Description / Table of Contents: Summary In a nutritional tolerance study 36 young dogs were fed over 52 weeks high or low purine diets at an average paired feeding intake of 0.6 and 80 mg purine-N/MJ per day. The high purine diet resulted in a significant decrease of growth rate by −23 % (Beagles) and −38 % (Dalmatians) and of feed efficiency (−29 and −42 %). The fasting levels of allantoin, uric acid and uracil in blood plasma were significantly increased. During the experiment a metabolic adaptation to the high purine diet decreased the plasma concentrations of uric acid, uracil and in part of allantoin. The high purine diet effected a significant increase of Km (2.5-fold) and of Vmax (1.6-fold) of uric transport through the erythrocyte membrane. The results documented disadvantageous effects of high purine nutrition during juvenile development.
    Notes: Zusammenfassung In einer Verträglichkeitsstudie erhielten 36 junge Hunde über 52 Wochen eine purinreiche oder purinarme Diät mit durchschnittlich 6 bzw. 80 mg Purin-N/MJ pro Tag bei gruppengleicher Aufnahme („paired feeding“). Die Hochpurin-Diät führte zu einer signifikanten Verminderung der Gewichtsentwicklung um −23% (Beagles) bzw. −38% (Dalmatiner) und der Futterverwertung (−29 bzw. −42%) sowie zu einer signifikanten Erhöhung der Nüchternwerte von Allantoin, Harnsäure und Uracil im Blutplasma. Während der Versuchsdauer machte sich eine metabolische Adaptation an die Hochpurin-Diät mit signifikanter Erniedrigung von Harnsäure, Uracil und teils auch Allantoin im Plasma bemerkbar. Die Hochpurin-Diät bewirkte eine signifikante Zunahme der Km (2,6fach) und Vmax (1,6fach) des Harnsäuretransports durch die Erythrozytenmembran. Die Ergebnisse belegen nachteilige Effekte purinreicher Ernährung während der Jugendentwicklung.
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    European journal of nutrition 36 (1997), S. 299-302 
    ISSN: 1436-6215
    Keywords: Energy retention ; protein retention ; fat retention ; growth ; body composition ; broilers ; Energieansatz ; Proteinansatz ; Fettansatz ; Wachstum ; Körperzusammensetzung ; Broiler
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Medicine
    Description / Table of Contents: Zusammenfassung Mit steigender Aufnahme erhöht sich der Körperfettgehalt und der Körperproteingehalt nimmt ab. Es wird oft angenommen, daß jede Zunahme im Ansatz mit mehr Fett und weniger Protein verbunden ist. Experimentelle Ergebnisse widerlegen jedoch diese Annahme. In zwei Experimenten mit männlichen Broilerhühnern wurden die Tiere auf einem Niveau von 60 % und 100 % der empfohlenen Energieaufnahme gefüttert. Die Körperzusammensetzung bei 1500 g zeigte, wie erwartet, daß sich bei steigenden Aufnahmen der Körperfettgchalt vergrößert und der Körperproteingehalt abnimmt. Fettund Proteinansatz waren linear mit der totalen Energieretention (ER) korreliert. Das bedeutet, daß jede Zunahme im Ansatz den gleichen Protein- und Fettgehalt besitzt. Wenn der Fettansatz gleich Null ist wird nur Protein, etwa 50 % des maximalen Ansatzes, retiniert. Wenn ER=O ist, wird Protein angesetzt und Fett mobilisiert. Energie-und N-Bilanzuntersuchungen bestätigen die konstante Zusammensetzung jeder Vergrößerung des Ansatzes. Die Ergebnisse beider Experimente zeigen, daß die ER aus zwei Komponenten besteht: einem basalen konstanten täglichen Proteinansatz und einer variablen zusätzlichen ER, die hauptsächlich aus Fett besteht. Der basale Proteinansatz beträgt etwa 50 % des maximalen Ansatzes. Mit steigenden Energieaufnahmen wird der basale Proteinansatz mit einer zusätzlichen Menge von Protein und Fett im konstanten Verhältnis ergänzt.
    Notes: Summary With increasing intakes the body fat content increases and that of protein decreases. It is most often assumed that this is brought about because each increment in retention contains more fat and less protein. Experimental results, however, showed that this explanation is not true. In two experiments male broiler chickens were fed at levels between 60 and 100 % of recommended energy intake. Body composition at 1500 g showed, as expected, that with increasing intakes body fat content increased and protein content decreased. Both fat and protein retention per day were linearly related to total energy retention (ER). This means that each increment in retention has the same protein and fat content. At zero fat retention only protein was retained, about 50 % of maximal retention. At zero ER protein was retained and fat mobilized. Energy and N balance experiments confirmed the constant composition of each increment in retention. The results of both experiments show that total ER consisted of two components: a basic constant daily protein retention and a variable additional ER, mainly consisting of fat. The basic protein retention is about half of maximal retention. With increasing energy intakes the basic protein retention is combined with an additional amount of protein and fat in a constant ratio.
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    European journal of nutrition 22 (1983), S. 14-26 
    ISSN: 1436-6215
    Keywords: branched chain α-keto acids ; 4-methyl-2-oxopentanoate, 3-methyl-2-oxopentanoate ; 3-methyl-2-oxobutyrate ; dehydrogenation ; transamination ; pharmacokinetics ; absorption
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Medicine
    Description / Table of Contents: Zusammenfassung Michaelis-Konstanten und Aktivitäten von Dehydrogenasen und Transaminasen der drei verzweigten α-Ketosäuren Keto-Valin, Keto-Leucin und Keto-Isoleucin in Leber, Niere, Skeletmuskel und Gehirn von Ratten werden mitgeteilt. Nach oraler Zufuhr passieren nur 11–22% der Ketosäuren unverändert die Leber. Aus pharmakokinetischen und Resorptions-Untersuchungen erhaltene Blutspiegel an Ketosäuren werden zu den Michaelis-Konstanten in Beziehung gesetzt. Bei den geringen Konzentrationen an Ketosäuren nach oraler Zufuhr kann angenommen werden, daß die oxidativen Prozesse in den nichthepatischen Geweben über die Transaminierung überwiegen. Daten über die Wachstumseffizienz von verzweigtkettigen α-Ketosäuren im Vergleich zu den entsprechenden Aminosäuren stimmen mit dieser Vorstellung überein. Bei intravenöser Verabreichung müßten die Voraussetzungen für Transaminierung besser sein als nach oraler Zufuhr. Auf der Basis von Daten aus der Literatur werden die Übertragbarkeit unserer Befunde auf den Menschen und die verschiedenen Faktoren, welche die Effizienz der verzweigten α-Ketosäuren durch Einwirkung auf ihren Stoffwechsel beeinflussen können, diskutiert.
    Notes: Summary Miehaelis-constants and enzyme activities for dehydrogenation and transamination of the three branched chainα-keto acids in liver, kidney, skeletal muscle, and brain of rats are reported. After oral load only 11–22 % of the keto acids pass the liver unchanged. Blood levels in pharmacokinetic and absorption studies are related to the Michaelis-constants. At the low keto-acid concentrations after oral application, dehydrogenation in the non-hepatic tissues is supposed to prevail over transamination. Data on feed efficiency of branched chain α-keto acids reported in the literature support this view. The chance for transamination is better after intravenous administration. The transferability of our data to humans, and various factors influencing the efficiency of branched chain α-keto acids are discussed in connection with data reported in the literature.
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    European journal of nutrition 36 (1997), S. 332-335 
    ISSN: 1436-6215
    Keywords: Nutrient intake ; protein metabolism ; protein synthesis ; growth ; energy expenditures ; Nährstoffaufnahme ; Proteinstoffwechsel ; Proteinsynthese ; Wachstum ; Energieaufwand
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Medicine
    Description / Table of Contents: Zusammenfassung Eine Zunahme von fettfreiem Gewebe tritt auf, wenn die Proteinsynthese größer ist als der Proteinabbau. Obwohl während des Wachstums von der Geburt bis zur Reife die absoluten Proteinsynthese- und -abbauraten ansteigen, nehmen dagegen die fraktionellen Raten ab. Bcide Prozesse reagieren auf die Nährstoffaufnahme. Es gibt aber deutliche Unterschiede zwischen den verschiedenen Geweben. Protein, Kohlenhydrate und Fett können den Proteinansatz bei unreifen Tieren und Kindern stimulieren. Die zugrundeliegenden Mechanismen und die Energieaufwendungen scheinen jedoch unterschiedlich zu sein.
    Notes: Summary Lean tissue growth occurs when the rate of protein synthesis exceeds the rate of protein breakdown. Althoughabsolute rates of protein synthesis and breakdown rise during growth from birth to maturityfractional rates fall. Both these processes are sensitive to nutrient intake but responses to feeding vary greatly amongst different tissues. Protein, carbohydrate and fat can all stimulate body protein accretion in immature animals and in children but the mechanisms by which they do so, and the energy expenditures involved, seem to be different.
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Empirical economics 24 (1999), S. 23-44 
    ISSN: 1435-8921
    Keywords: Key words: Cointegration ; convergence ; growth ; Kalman filter ; JEL classifications: C22 ; O47 ; O57
    Source: Springer Online Journal Archives 1860-2000
    Topics: Economics
    Notes: Abstract. Augmented Dickey Fuller (ADF) and Kalman filter convergence tests are applied to annual GDPs per head to 16 industrialised countries from 1890 to 1989. Results favour convergence towards the US with a structural break following the Second World War. Estimates suggest that steady-states were higher after the war and that speeds of convergence are different across countries. The Kalman filter method dismissed the no convergence hypothesis more often than its ADF counterpart. This could explain the apparent contradiction in earlier empirical work on similar data sets (cross-section methods tended to favour convergence while time series methods were unable to dismiss the no convergence hypothesis.)
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  • 9
    ISSN: 1570-7458
    Keywords: Vitis vinifera ; Empoasca vitis ; leafhopper ; photosynthesis ; transpiration ; stomatal conductance ; mesophyll conductance ; growth ; yield ; fruit quality ; starch ; carbohydrate reserves
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The impact of the grape leafhopper,Empoasca vitis, on leaf gas exchange, plant growth, yield, fruit quality and carbohydrate reserves of the grapevines,Vitis vinifera L., was studied. Gas exchange was measured on the discolored (red) and the green parts of infested main leaves and on leaves from uninfested vines. Photosynthesis and mesophyll conductance were severely reduced on main leaves showing leafhopper feeding symptoms. The stomatal conductance of the red leaf section of infested main leaves was lower than on undamaged control leaves. Additionally, the red leaf section of infested main leaves showed lower transpiration rates when compared to the green parts of the same leaves and to undamaged control leaves. Gas exchange processes of lateral leaves were not affected by leafhopper feeding. Leafhopperload on main leaves was correlated to visual damage symptoms. At 71.8 leafhopper-days per leaf up to 40% of the main leaf area of the infested plants was discolored from the borders towards the center. Lateral leaves showed no feeding symptoms. Shoot diameter, pruning weight and carbohydrate reserves in the wood were not affected by leafhoppers. Lateral leaf area growth was significantly stimulated on plants infested by leafhoppers. No decrease in yield and fruit quality with leafhopper-loads up to 71.8 leafhopper-days per leaf were observed.
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Entomologia experimentalis et applicata 80 (1996), S. 141-144 
    ISSN: 1570-7458
    Keywords: Polygonia c-album ; Nymphalidae ; host-plant selection ; growth ; size
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
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