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  • pharmacokinetics  (2,025)
  • Molecular biophysics
  • Springer  (2,055)
  • American Physical Society  (1)
  • Periodicals Archive Online (PAO)
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  • 1
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    Entropy-driven formation of a chiral liquid-crystalline phase of helical filaments (2006)
    American Physical Society
    Details
    Publication Date: 2022-05-25
    Description: Author Posting. © The Authors, 2006. This article is posted here by permission of American Physical Society for personal use, not for redistribution. The definitive version was published in Physical Review Letters 96 (2006): 018305, doi:10.1103/PhysRevLett.96.018305.
    Description: We study the liquid-crystalline phase behavior of a concentrated suspension of helical flagella isolated from Salmonella typhimurium. Flagella are prepared with different polymorphic states, some of which have a pronounced helical character while others assume a rodlike shape. We show that the static phase behavior and dynamics of chiral helices are very different when compared to simpler achiral hard rods. With increasing concentration, helical flagella undergo an entropy-driven first order phase transition to a liquid-crystalline state having a novel chiral symmetry.
    Description: M. S. and R. O. are supported by NIH Grant No. EB002583.
    Keywords: Entropy ; Molecular biophysics ; Liquid crystal phase transformations ; Symmetry ; Chirality
    Repository Name: Woods Hole Open Access Server
    Type: Article
    Format: 765344 bytes
    Format: application/pdf
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  • 2
    Electronic Resource
    Electronic Resource
    Human Interindividual Variability in Parameters Related to Health Risks (1999)
    Springer
    Risk analysis 19 (1999), S. 711-726 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1007045922532
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  • 3
    Electronic Resource
    Electronic Resource
    Evaluation of the Uncertainty in an Oral Reference Dose for Methylmercury Due to Interindividual Variability in Pharmacokinetics (1999)
    Springer
    Risk analysis 19 (1999), S. 547-558 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1007017116171
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  • 4
    Electronic Resource
    Electronic Resource
    Das Rückstandsverhalten von Chloramphenicol nach intramuskulärer Applikation beim Schwein (1985)
    Springer
    European journal of nutrition 24 (1985), S. 113-119 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02020458
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  • 5
    Electronic Resource
    Electronic Resource
    Enzymatic and pharmacokinetic studies on the metabolism of branched chain α-keto acids in the rat (1983)
    Springer
    European journal of nutrition 22 (1983), S. 14-26 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02020781
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  • 6
    Electronic Resource
    Electronic Resource
    The lymphatic route. 1) Albumin and hyaluronidase modify the normal distribution of interferon in lymph and plasma (1986)
    Springer
    Cellular and molecular life sciences 42 (1986), S. 432-433 
    Details
    ISSN: 1420-9071
    Keywords: Interferon ; immunomodulator ; catabolism ; pharmacokinetics ; administration routes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary When human recombinant interferon-α2 diluted in saline was injected s.c. into rabbits, the total amount recovered in thoracic lymph was less than 0.4%. Recoveries increased from 2- to 8-fold if interferon was injected in 4% albumin or with hyaluronidase, respectively. Albumin added to interferon acts as an interstitial fluid expander, thus favoring interferon absorption through lymphatics rather than blood capillaries. This strategy may increase the therapeutic index of interferon.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02118644
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  • 7
    Electronic Resource
    Electronic Resource
    Pseudoelectrostatic effects in the thermodynamics of dye binding to DNA (1985)
    Springer
    Il nuovo cimento della Società Italiana di Fisica 6 (1985), S. 593-608 
    Details
    ISSN: 0392-6737
    Keywords: Chemical thermodynamics ; Molecular biophysics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Description / Table of Contents: Riassunto In questo lavoro è stata studiata l'interazione fra bromuro di etidio (EB) e DNA in soluzione acqua-metanolo a varie temperature. Si è trovato che l'energia libera di Gibbs associata al legame DNA-EB può essere ben descritta da una relazione lineare nella costante dielettrica della soluzione, come visto anche per altri alcoli. Il ruolo dell'entalpia e dell'entropia di legame è piú semplice se queste quantità sono ricavate isodielettricamente (ε = costance). Con questa procedura, inoltre, è possibile separare le proprietà del solvente dalle caratteristiche del legame DNA-EB mostrando con chiarezza la presenza d'interazioni idrofobiche.
    Abstract: Резюме Исследуется взаимодействие ДНК с бромистым этидием (EB) в присутствии метанола ири различных температурах. Найдено, что свободная энергия Гиббса в случае связи ДНК-ЕВ линейно зависит от диэлектрической постоянной раствора. Указанное свойство обнаружено и для других спиртов. При рассмотрении энтальпии и энтропии в случае связи ДНК-ЕВ установлено, что их роль становится довольно простой, если их изменение осушествляется изодиэлектрически (ε=const). С помощью этой методики можно отличитя свойства, обусловленные растворителем, от свойств, овусловлениых взаимодействием ДНК и ЕВ. Таким образом, можно установить наличие гидрофобного взаимодействия.
    Notes: Summary The interaction of DNA with the dye ethidium bromide (EB) has been investigated under the presence of methanol at varying temperatures. The Gibbs free energy associated with the DNA-EB binding is found to be well described by its linear dependence upon the dielectric constant of the solution, a property also found for other alcohols. When the enthalpy and entropy associated with the binding are considered, it is found that their role becomes rather simple if their evaluation is performed isodielectrically (ε=const). According to this procedure, the varying properties of the solvent can be separated from those of the interacting DNA and EB and the presence of hydrophobic interactions becomes then well established.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02450595
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  • 8
    Electronic Resource
    Electronic Resource
    DNA melting induced by alcohols: Role of the solvent properties (1985)
    Springer
    Il nuovo cimento della Società Italiana di Fisica 6 (1985), S. 618-630 
    Details
    ISSN: 0392-6737
    Keywords: Chemical thermodynamics ; Molecular biophysics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Description / Table of Contents: Riassunto Si è studiata la denaturazione isoterma del DNA da timo di vitello indotta dalla presenza di quattro alcoli semplici in soluzione. Sono state eseguite sia misure a 67.2 °C, temperatura alla quale la frazione denaturata senza alcoli vale circa 20%, che profili di ≪fusione≫ a temperature variabili. I risultati mostrano che, al crescere della concentrazione e del gruppo alchilico degli alcoli la denaturazione dapprima raggiunge un valore massimo e poi torna indietro. Questo comportamento, attribuito alle proprietà ≪insolite≫ dell'acqua come risulta anche da misure di compressibilità indica che gli effetti idrofobici ed elettrostatici intervengono in modo complicato.
    Abstract: Резюме Исследуется изотермическая денатурация DNA тимуса, индуцированная наличием моногидридных спиртов в растворе. Измерения проводятся при температуре 67.2 °C, при которой денатурация в присутствии спиртов составляет около 20%. Также регистрируются профили плавления при различных температурах. Полученные результаты показывают, что при увеличении концентрации мума, а затем убывает. Это поведение, приписываемое свойствам ≪необыкновенной≫ воды, что получено также из измерений сжимаемости, указывает, что гидрофобные и электростатические эффекты связаны сложным образом.
    Notes: Summary The isothermal denaturation of calf thymus DNA, induced by the presence of some monohydric alcohols in the solution, was investigated. Measurements were performed at a temperature (67.2°C) at which the denaturation, in the absence of alcohols, is about 20% and melting profiles at varying temperatures were also recorded. Results show that with increasing alcohol concentration and alkyl group size DNA denaturation first reaches a maximum and then falls back. This behaviour, ascribed to «unusual» water properties as inferred also from compressibility measurements, indicates that hydrophobic and electrostatic effects are connected in a complex way.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02450597
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  • 9
    Electronic Resource
    Electronic Resource
    Optical spectroscopic study of the Cu(II) complexes with adenosine and adenine nucleotides (1985)
    Springer
    Il nuovo cimento della Società Italiana di Fisica 5 (1985), S. 348-357 
    Details
    ISSN: 0392-6737
    Keywords: Molecular biophysics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Description / Table of Contents: Riassunto La formazione dei complessi di rame (II) con molecole di adenosina-5′-monofosfato (AMP), adenosina-5′-difosfato (ADP), adenosina-5′-trifosfato (ATP) e con polifosfati inorganici è stata studiata in soluzione acquosa, nell’intervallo dipH da 3 a 12, analizzando l’effetto del campo legante sulle transizioni ottiche tra livellid dello ione Cu(II). I risultati mostrano, al variare delpH, l’esistenza di diversi complessi tra loro in equilibrio in relazione allo stato di ionizzazione dell’adenina e dei gruppi fosfato e ribosio. In particolare, per valori dipH maggiori di 8, il rame interagisce con il gruppo ribosio dei ribonucleotidi esaminati, mentre tale interazione non si osserva nel caso dei corrispondenti desossiribonucleotidi.
    Notes: Summary The interaction of copper(II) with the 5′-nucleotides: adenosine monophosphate (AMP), adenosine diphosphate (ADP), adenosine triphosphate (ATP) and with inorganic polyphosphate solutions has been studied as a function ofpH in thepH range 3 to 12. Our approach is the study of the effects that the field of ligands produces on the opticald-d transitions of the cupric ion. The results show that the Cu(II)-adenosine phosphate complexes exist in a variety of forms in equilibrium, the percentage of each species varying according to the state of ionization of the intrinsic adenine, phosphate and ribose groups. AtpH values greater than 8 an interaction becomes manifest between the copper ions and the hydroxyl groups of ribose, while this effect is not observed in the case of the Cu(II)-deoxyadenosine systems.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02451255
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  • 10
    Electronic Resource
    Electronic Resource
    1H NMR study of water relaxation and self-diffusion in human serum albumin aqueous solutions (1991)
    Springer
    Il nuovo cimento della Società Italiana di Fisica 13 (1991), S. 261-271 
    Details
    ISSN: 0392-6737
    Keywords: Diffusion and ionic conduction in liquids ; Nuclear magnetic resonance and relaxation ; Molecular biophysics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Summary Water proton spin-lattice relaxation and self-diffusion in aqueous solutions of human serum albumin have been studied by1H NMR as a function of the protein concentration. Spin-lattice relaxation data, which display a nonlinear behaviour with the protein concentration, could be fitted with a two-phase model taking into account the experimentally determined hydration («bound») water values. Despite a similar trend is registered for the water self-diffusion coefficient, such a model has been found unable to explain the related experimental data taken as a function of the biomolecule concentration. On the other hand, the solute-induced proton self-diffusion decrease could be satisfactorily interpreted by postulating an enhanced probability of hydrogen-bond formation occurring within the «vicinal» water surrounding the biomolecules for several hydration shells. The consistency within the two models is discussed in connection with the magnetic interactions occurring within the solute-solvent systems.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02456954
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