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  • pharmacokinetics  (2,025)
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  • 1
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    Springer Nature | Springer
    Publication Date: 2024-04-05
    Description: This open access book offers the first comprehensive account of the pan-genome concept and its manifold implications. The realization that the genetic repertoire of a biological species always encompasses more than the genome of each individual is one of the earliest examples of big data in biology that opened biology to the unbounded. The study of genetic variation observed within a species challenges existing views and has profound consequences for our understanding of the fundamental mechanisms underpinning bacterial biology and evolution. The underlying rationale extends well beyond the initial prokaryotic focus to all kingdoms of life and evolves into similar concepts for metagenomes, phenomes and epigenomes. The book’s respective chapters address a range of topics, from the serendipitous emergence of the pan-genome concept and its impacts on the fields of microbiology, vaccinology and antimicrobial resistance, to the study of microbial communities, bioinformatic applications and mathematical models that tie in with complex systems and economic theory. Given its scope, the book will appeal to a broad readership interested in population dynamics, evolutionary biology and genomics.
    Keywords: Microbial Genetics and Genomics ; Evolutionary Biology ; Genetics and Population Dynamics ; Microbial Ecology ; Human Genetics ; Genetics and Genomics ; Comparative genomics ; Metagenomics ; Microbial Population Analysis ; Pangenome Profile ; Supra-Genome Analysis ; Adaptive Evolution ; Computational Tools ; Bioinformatic Genomics ; Core Dispensable Genome ; Selection, Recombination, Composition ; Acquired Resistance ; Bacterial Species Concept ; Genomic Diversity ; Bacterial Ecology, Microevolution ; Open Access ; Pan-metagenomics ; Pan-microbiomics ; Pan-epigenome ; Gene Transfer ; Pan-phenomes ; Microbiology (non-medical) ; Genetics (non-medical) ; Evolution ; Applied mathematics ; Ecological science, the Biosphere ; Medical genetics ; thema EDItEUR::P Mathematics and Science::PS Biology, life sciences::PSG Microbiology (non-medical) ; thema EDItEUR::P Mathematics and Science::PS Biology, life sciences::PSA Life sciences: general issues::PSAJ Evolution ; thema EDItEUR::P Mathematics and Science::PB Mathematics::PBW Applied mathematics ; thema EDItEUR::P Mathematics and Science::PS Biology, life sciences::PSA Life sciences: general issues::PSAF Ecological science, the Biosphere ; thema EDItEUR::M Medicine and Nursing::MF Pre-clinical medicine: basic sciences::MFN Medical genetics ; thema EDItEUR::P Mathematics and Science::PS Biology, life sciences::PSA Life sciences: general issues::PSAK Genetics (non-medical)
    Language: English
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  • 2
    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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  • 3
    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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  • 4
    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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  • 5
    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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  • 6
    Electronic Resource
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    Springer
    Acta biotheoretica 33 (1984), S. 35-50 
    ISSN: 1572-8358
    Keywords: Evolution ; falsification ; Darwinism ; philosophy of science
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract In this paper we discuss the epistemological positions of evolution theories. A sharp distinction is made between the theory that species evolved from common ancestors along specified lines of descent (here called “the theory of common descent”), and the theories intended as causal explanations of evolution (e.g. Lamarck's and Darwin's theory). The theory of common descent permits a large number of predictions of new results that would be improbable without evolution. For instance, (a) phylogenetic trees have been validated now; (b) the observed order in fossils of new species discovered since Darwin's time could be predicted from the theory of common descent; (c) owing to the theory of common descent, the degrees of similarity and difference in newly discovered properties of more or less related species could be predicted. Such observations can be regarded as attempts to falsify the theory of common descent. We conclude that the theory of common descent is an easily-falsifiable & often-tested & still-not-falsified theory, which is the strongest predicate a theory in an empirical science can obtain. Theories intended as causal explanations of evolution can be falsified essentially, and Lamarck's theory has been falsified actually. Several elements of Darwin's theory have been modified or falsified: new versions of a theory of evolution by natural selection are now the leading scientific theories on evolution. We have argued that the theory of common descent and Darwinism are ordinary, falsifiable scientific theories.
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  • 7
    Electronic Resource
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    Springer
    Acta biotheoretica 35 (1986), S. 77-106 
    ISSN: 1572-8358
    Keywords: Evolution ; nonequilibrium thermodynamics ; boundary conditions models ; initial conditions models
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Proponents of two axioms of biological evolutionary theory have attempted to find justification by reference to nonequilibrium thermodynamics. One states that biological systems and their evolutionary diversification are physically improbable states and transitions, resulting from a selective process; the other asserts that there is an historically constrained inherent directionality in evolutionary dynamics, independent of natural selection, which exerts a self-organizing influence. The first, the Axiom of Improbability, is shown to be nonhistorical and thus, for a theory of change through time, acausal. Its perception of the improbability of living states is at least partially an artifact of closed system thinking. The second, the Axiom of Historically Determined Inherent Directionality, is supported evidentially and has an explicit historical component. Historically constrained dynamic populations are inherently nonequilibrium systems. It is argued that living, evolving systems, when considered to be historically constrained nonequilibrium systems, do not appear improbable at all. Thus, the two axioms are not compatible. Instead, the Axiom of Improbability is considered to result from an unjustified attempt to extend the contingent proximal actions of natural selection into the area of historical, causal explanations. It is thus denied axiomatic status, and the effects of natural selection are subsumed as an additional level of constraint in an evolutionary theory derived from the Axiom of Historically Determined Inherent Directionality.
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  • 8
    ISSN: 1572-8358
    Keywords: Animal cognition ; Evolution ; Representation ; Computation ; Significance ; Phenomenology ; Autonomy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract A distinction is made between two definitions of animal cognition: the one most frequently employed in cognitive sciences considers cognition as extracting and processing information; a more phenomenologically inspired model considers it as attributing to a form of the outside world a significance, linked to the state of the animal. The respective fields of validity of these two models are discussed along with the limitations they entail, and the questions they pose to evolutionary biologists are emphasized. This is followed by a presentation of a general overview of what might be the study of the evolution of knowledge in animals.
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  • 9
    Electronic Resource
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    Springer
    Monatshefte für Chemie 125 (1994), S. 1033-1039 
    ISSN: 1434-4475
    Keywords: Prebiotic peptide formation ; Evolution ; Clay catalysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Description / Table of Contents: Zusammenfassung Die Fähigkeit von Tonmineralien der Montmorillonitklasse zur Katalyse von Peptidbildungsreaktionen aus Aminosäuren in wäßriger Lösung wurde am Beispiel von Glyzin und Kupfer sowie Kalzium und Morillonit untersucht. Experimente mit Verdampfungszyklen haben gezeigt, daß kleinere Mengen von Di- und Tripeptiden aus der Aminosäure gebildet werden. Die weitere Polymerisation von Dipeptiden hingegen scheint wesentlich leichter in diesem Reaktionssystem zu verlaufen als der Anfangsschritt der Bildung des Dipeptides. Eine mögliche Rolle von Tonmineralien in der präbiotischen Peptidevolution kann daher in der Verlängerung von Peptidketten gesehen werden. Kupferionen in der Tonmatrix zeigen keinerlei Vorteile gegenüber den üblichen Kalziumionen, die in natürlichem Montmorillonit vorkommen.
    Notes: Summary The ability of montmorillonite clay minerals for catalyzing peptide formation from amino acids in aqueous solution has been investigated using glycine and Cu2+ and Ca2+ containing montmorillonites as reaction systems. Evaporation cycle experiments showed that minor amounts of di- and tripeptide are formed from the amino acid. Further polymerization of dipeptide, however, seems to be more favoured by this reaction system than the initial step of dipeptide formation, and a possible role of clays in prebiotic peptide evolution could be seen therefore in the prolongation of peptide chains. Cu2+ ions in the clay matrix did not show any advantage over the usual Ca2+ ions embedded in natural montmorillonite.
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  • 10
    ISSN: 1433-4909
    Keywords: Key words Thermococcus ; Pyrococcus ; Thermophilic ; Phosphofructokinase ; Evolution ; ADP ; Glycolysis ; ATP
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The ADP-dependent phosphofructokinase (PFK) from Thermococcus zilligii has been purified 950 fold; it had a specific activity of 190 U mg−1. The enzyme required Mg2+ ions for optimal activity and was specific for ADP. The forward reaction kinetics were hyperbolic for both cosubstrates (pH optimum of 6.4), and the apparent K m values for ADP and fructose-6-phosphate were 0.6 mM (apparent V max of 243 U mg−1) and 1.47 mM (apparent V max of 197 U mg−1), respectively. Significantly, the enzyme is indicated to be nonallosteric but was slightly activated by some monovalent cations including Na+ and K+. The protein had a subunit size of 42.2 kDa and an estimated native molecular weight of 66 kDa (gel filtration). Maximal reaction rates for the reverse reaction were attained at pH 7.5–8.0, and the apparent K m values for fructose-1,6-bisphosphate and AMP were 0.56 mM (apparent V max of 2.9 U mg−1) and 12.5 mM, respectively. The biochemical characteristics of this unique ADP-dependent enzymatic activity are compared to ATP and pyrophosphate-dependent phosphofructokinases.
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