A mathematical evaluation of dose-dependent PpIX fluorescence kinetics in vivo

The in vivo pharmacokinetics of protoporphyrin IX (PpIX) after administration of 5-aminolevulinic acid (ALA) cannot be described accurately by mathematical models using first-order rate processes. We have replaced first-order reaction rates by dose-dependent (Michaelis-Menten [MM]) reaction rates in a mathematical compartment model. Different combinations of first-order and dose-dependent reaction rates were evaluated to see which one would improve the goodness-of-fit to experimentally determined in vivo PpIX fluorescence kinetics as a function of concentration. The mathematical models that were evaluated are all based on a three-compartment model for drug distribution, conversion to PpIX and subsequent conversion to heme. Implementation of dose-dependent reaction rates improved the goodness-of-fit and enabled interpolation to other drug doses. For most data sets the time constant for delivery to the target cells turned out to be dose dependent. For all data sets the use of MM rates for the conversion of ALA to PpIX yielded better fits. The clearance of PpIX turned out to be a first-order process for all doses and types of administration. Fluorescence curves measured on a specific tissue type but obtained in different studies with different measurement techniques could be described with a single set of parameters.     

Radiation degradation of copolymers of methyl methacrylate and 3-oximino-2-butanone methacrylate

Copolymers of methyl methacrylate and 3-oximino-2-butanone methacrylate (OM) were investigated as deep-UV and e-beam resists. Their increased sensitivity relative to PMMA (up to 50 times) was correlated with the radiation chemical yields of the volatile products and main chain scissions. The degradation of these copolymers, activated by the 3-oximino-2-butanone entity, is discussed in terms of energy absorption mechanisms and the subsequent scission reactions.     

Bisorthoesters as polymer intermediates. II. A facile method for the preparation of polybenzimidazoles

Aromatic bisorthoesters were found to be good polymer intermediates and could be condensed with aromatic tetramines under mild conditions, in DMSO at 100°C in a relatively short reaction time to give polybenzimidazoles. The hexapropyl orthoesters of terephthalic and isophthalic acid were the preferred aromatic orthoesters because they were relatively easily purified by vacuum distillation to polymer grade intermediates, since they are liquids. Higher orthoesters distill even under good vacuum near or above the decomposition temperature of the orthoester group. Hexaethyl orthooxalate was also used and is a very useful and stable derivative of oxalic acid, which can be used for condensation reactions. These three orthoesters were used for condensations with 3,3′,4,4′-tetraaminobiphenyl, 1,2,3,4-tetraaminobenzene, 3,3′,4,4′-tetraaminobiphenyl ether, and 3,3′,4,4′-tetraaminobenzophenone. All polybenzimidazoles were obtained in high to quantitative yields and with varying molecular weights (η_inh = 0.1?0.8 dl/g), which in some cases were in the fiber forming range.     

On the photometric determination of trivalent rhodium with eriochromecyanine RC

Summary Eriochromecyanine RC has been used as chromogenic reagent for the photometric determination of rhodium(III) on a micro scale. A coloured Rh(III)-ECRC chelate with _max 530 nm at pH 4.0 (25°C) is formed. A detailed study has been made concerning to characteristics, composition and stability of the chelate. Standard deviation was ±1.17%.

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Über die photometrische Bestimmung von dreiwertigem Rhodium mit Eriochromcyanin RC

Zusammenfassung Ergebnisse einer Untersuchung über die Zusammensetzung und Stabilität des Komplexes werden mitgeteilt. Das Absorptionsmaximum liegt bei 530 nm (pH 4,0; 25°C). Bestimmungen konnten mit einer Standardabweichung von ±1,17% durchgeführt werden.

     

THE EFFECTS OF HOST-CELL REACTIVATION ON ASSAY OF U.V.-IRRADIATED HAEMOPHILUS INFLUENZAE TRANSFORMING DNA

Abstract— The host cell reactivation (HCR) mechanism in Haemophilus influenzae cells is inhibited by sub-microgram concentrations of acriflavine (as is already known to be true for Escherichia coli ). Exposure of these cells to similar concentrations of the drug during bacterial transformation increases the apparent ultraviolet light (u.v.) sensitivity of previously irradiated transforming DNA, indicating a repair of this DNA after uptake by the cells under normal conditions. Repair is inhibited by applying acriflavine at any time up to one hour after competent cells contact the irradiated transforming DNA. The fraction of the u.v. damage repaired by HCR is very different for different genetic markers. Those markers which are most u.v. sensitive when assayed in the absence of acriflavine are most poorly repaired, suggesting that this is the reason for their higher sensitivity. For all markers the fraction of the damage repairable by in vitro photoreactivation is approximately constant, and strongly overlaps the damage repairable by HCR. The degree of HCR achieved can be altered by experimental treatment of the H. influenzae DNA prior to transformation. Thus treatment of irradiated DNA with an enzyme from Micrococcus lysodeikticus –known to attack u.v. damaged, but not undamaged DNA–prevents subsequent intracellular repair of the same u.v. lesions whose repair is inhibited by acriflavine. Similarly, partial replacement of the thymine in transforming DNA by 5-bromouracil (BU) strongly inhibits repair of subsequent u.v. damage. As in bacteriophage, the BU effect is relieved if the u.v. exposure occurs in the presence of cysteamine. It is clear that intracellular repair must be considered in interpreting experiments with u.v.-irradiated transforming DNA.     

Treatment of cutaneous T cell lymphoma with extracorporeal photopheresis induces Fas-ligand expression on treated T cells,but does not suppress the expression of co-stimulatory molecules on monocytes

Following extracorporeal photopheresis (ECP), lymphocytes become apoptotic and upregulate class I MHC antigenic peptides. Conversely, ECP treated monocytes demonstrate activation markers and have an increased avidity for the phagocytosis of apoptotic T cells. Processing of apoptotic T cells by monocytes, following ECP, is thought to induce an immunomodulatory response, which targets untreated, but clonal T cells. Recently we detected apoptotic lymphocytes immediately post ECP. Although enhanced CD95 (Fas) expression has been observed 24 h post ECP, CD95 and Fas-ligand (Fas-L) expression have not been determined at this very early apoptotic stage. Exposure of monocytes to UV has previously suppressed expression of the co-stimulatory molecules required for the presentation of processed antigens to T cells. Our data demonstrate no increase in CD95 or Fas-L expression on T cells tested immediately following ECP. However, the number of T cells expressing Fas-L significantly increased 24 h post ECP (P<0.005). The expression of the co-stimulatory molecules, CD54, CD80 and CD86, remained unaltered on monocytes treated by ECP. Although the mechanism responsible for early induction of lymphocyte apoptosis remains unclear, the later apoptosis involves Fas-L expression. The maintenance of co-stimulatory molecules, on treated monocytes, indicates that they retain the ability to induce an immunomodulatory response.     

Über die Stereochemie der Hydrogenolyse von N-Benzyl-Bindungen I. Die Hydrogenolyse von Derivaten der 2-Amino-2-phenyl-propionsäure.

The stereochemistry of the hydrogenolysis of benzyl-N bonds was studied using S(+)-2-dimethylamino-2-phenyl-propionic acid (I) and its derivatives, and R(?)-2-anilino-2-phenyl-propionic acid (II). The configuration of I was confirmed, that of II established by ORD. measurements, after transformation of the phenyl into cyclohexyl groups. On a palladium catalyst the hydrogenolysis of I, its methyl and ethyl esters and its amide proceeded with 72 to 99% inversion of configuration, that of II with at least 66% inversion. The ester of the quaternary ammonium derivative of I gave as much inversion as retention (= racemisation).     

The effect of metal oxides on the oxidation of polybutadiene

Carboxy-terminated polybutadiene (CTPB) was oxidised as a coating on various metal oxides by heating in air on a thermobalance. The oxidation was found to be free from diffusion control and was catalysed by certain of the oxides. The catalysis was shown to be independent of semiconductor type and to be associated with those oxides for which the width of the forbidden zone between the valence and conduction bands (U) is less than 1.9 eV. In general, low values of U result in high catalytic activity. It is proposed that catalysis occurs by a redox mechanism, viz. RO₂H + p → RO₂^. + H⁺, RO₂H + e → RO^. + OH^?.     

Radical reactions involving esters of fumaric acid—III. Chain transfer processes

Model compounds have been used in studies at 60° in connection with transfer to polymer during the copolymerization of vinyl acetate with esters of fumaric acid. Succinate esters were used to simulate the fumarate ester units and ethyl acetate the vinyl acetate units in the copolymers. The succinate esters are much more reactive than ethyl acetate in transfer reactions with polyvinyl acetate radicals. Methyl isobutyrate and methyl propionate were also examined to assess the difference in reactivity in transfer of tertiary and secondary hydrogen atoms. It is concluded that branching is a very important reaction in the preparation of high conversion copolymers of fumarate esters with vinyl acetate.     

Reactions of Titanium Alkoxides with N-Methylaminoalcohols

N-methylaminoalkoxides of titanium of the type Ti(OR)_4?n(O · CHR′ · CH₂ · NR″R?)_n where R = Et and Pr¹; n = 1–4; and R′ = R″ = H, R? = Me; R′ = H, R″ = R? = Me; R′ = R″ = R? = Me, synthesized by the reactions of titanium alkoxides with aminoalcohols, show interesting variations in their properties like physical state, volatility and molecular complexity. I.r. and p.m.r. spectra of these derivatives have been recorded. A few interchange reactions with methanol and tert-butanol have also been carried out. These aminoalkoxides get cleaved with acetyl chloride and undergo insertion reactions with phenylisocyanate, thus providing the first examples of insertion reactions in such derivatives.