Limit on tau decay to seven charged particles.
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Journal Article↗
Biomedical subjects
J Brom
Publications and source records attributed to J Brom.
Metabolism of leukotriene B4 by polymorphonuclear granulocytes of severely burned patients.
Leukotriene B4 release from polymorphonuclear granulocytes of severely burned patients was reduced as compared to healthy donor cells. This decrease is due to an enhanced conversion of LTB4 into the 20-hydroxy- and 20-carboxy-metabolites and further to a decreased LTB4-synthesis. In addition, studies on the exogenous LTB4-conversion revealed an unidentified compound which was derived from LTB4. Our data suggest a modulation of the enzymatic activities involved in omega-oxidation of LTB4 (isoenzymes of cytochrome P-450).
Adult↗
Altered arachidonic acid metabolism in granulocytes of polytraumatized patients.
The generation and metabolism of leukotrienes (LTs) from polymorphonuclear granulocytes of four polytraumatic patients on stimulation with the Ca-Ionophore A 23187 were studied by high performance liquid chromatography. In contrast to healthy donors the concentration of LTB4 within the supernatant of the stimulated granulocytes from these patients is reduced. The ratio of LTB4 versus the combined amounts of the biologically inactive 6-trans and 12-epi-6-trans-isomers is significantly decreased. In one patient who suffered from an Adult Respiratory Distress Syndrome (ARDS) a pronounced enhancement of LTC4 synthesis was observed.
Calcimycin↗
Characterization of leukotriene B4-omega-hydroxylase activity within human polymorphonuclear granulocytes.
Human polymorphonuclear granulocytes (PMN) metabolize exogenous [3H]leukotriene B4 (LTB4) into 20-hydroxy- and 20-carboxy-[3H]LTB4. The conversion was enhanced at acidic pH values (pH 6.0-7.0). Sonication of purified PMN and subcellular fractionation by differential centrifugation showed that major LTB4-hydroxylase activity was associated with the microsomal fraction (105,000 g pellet). In contrast to intact cells, LTB4-hydroxylase activity within the microsomal fraction revealed optimal activity at neutral pH and was inhibited by a wide range of divalent cations. There was a strict requirement for the presence of suitable electron donors such as NADPH. Heterocyclic nitrogenous bases, such as imidazole and pyridine, inhibited the LTB4 conversion induced by intact PMN as well as by their microsomes. These observations combined with the spectrophotometric analysis (carbon monoxide dithionite-reduced difference spectrum) supported the assumption that LTB4-hydroxylase resembled a cytochrome P-450 enzyme. The LTB4-hydroxylase within human PMN was not identical with the cytochrome P-450 of rat liver; hepatic microsomes only showed minute conversion of LTB4.
Animals↗
Effect of tenoxicam and indomethacin on the release of histamine, prostaglandin E2 and leukotrienes from various cells.
Tenoxicam and indomethacin were studied with regard to their effects to modulate mediator release (histamine, prostaglandin E2 (PGE2) mono-hydroxyeicosatetraenoic acids, leukotrienes) from various cells. For histamine release human lymphocytes, monocytes, and basophils were analyzed with either anti-IgE or the calcium ionophore A 23187. Rat mast cells were stimulated with the calcium ionophore A 23187. With tenoxicam significant inhibition of histamine release was obtained as compared to the effects of indomethacin. Enhancement of histamine release at defined concentrations was more often observed with indomethacin than with tenoxicam. At high concentrations of indomethacin the formation of the radiolabelled phospholipids and 5S-hydroxy-6-trans-8,11,14-cis-eicosatetraenoic acid (14C-arachidonic acid metabolites) from stimulated human polymorphonuclear neutrophilic leukocytes was inhibited. With regard to endogenous leukotriene and PGE2 release tenoxicam inhibited leukotrienes B4 and C4 and PGE2 release. Tenoxicam appeared to be more active than indomethacin.
Animals↗
Observation of tensor and scalar mesons produced in e+e- annihilation at 29 GeV.
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Journal Article↗
Studies on the degradation of imipenem within serum and a renal kidney fraction.
The degradation of imipenem in vitro was analyzed using reversed-phase HPLC. The incubation of imipenem with a microsomal kidney fraction revealed the generation of two metabolites (UV-maxima at 275 or 308 nm, respectively). The metabolism of imipenem by the renal enzyme was completely inhibited by cilastatin (2 micrograms/ml). The lowest detectable inhibitory concentration of cilastatin was at 6.5 X 10(-10) M. The recovery of imipenem from serum was 52.6% after incubation for 2 h at 37 degrees C. The stability of the antibiotic within serum was improved by 13.9% in the presence of EDTA (10 mM) indicating a possible involvement of serum dipeptidases in the systemic breakdown of the imipenem molecule.
Animals↗
Cilastatin (MK 0791) is a potent and specific inhibitor of the renal leukotriene D4-dipeptidase.
The metabolism of leukotriene D4 to leukotriene E4 by a dipeptidase of kidney tissue is strongly inhibited by cilastatin (MK 0791) a known renal dehydropeptidase-I inhibitor. The comparison with similar enzyme activities from other tissues (liver, lung, serum, polymorphonuclear granulocytes) revealed a high specificity of cilastatin for the kidney enzyme which was found to be associated with the microsomal fraction. The lowest detectable inhibitory concentration of cilastatin within renal tissue was 8 X 10(-8)M.
Animals↗
Functional characteristics of leukotriene C4- and D4-metabolizing enzymes (gamma-glutamyl transpeptidase, dipeptidase) within human plasma.
Several properties of the leukotriene C4- and leukotriene D4-metabolizing enzymes within human plasma were studied after fractionation of the plasma proteins using ammonium sulfate precipitation. Leukotriene D4-metabolizing enzymes were widely distributed among the fractions obtained. They showed different pH optima (pH 6.5, pH 7.0 and pH greater than or equal to 8.5) and revealed a different degree of thermal stability. The results indicate the presence of more than one enzyme in plasma which interacts with leukotriene D4. EDTA and L-cysteine inhibited the metabolism of leukotriene D4. Two leukotriene C4-metabolizing activities (gamma-glutamyl transpeptidases) differing in their molecular weights were detected after gel filtration. Their molecular weights were estimated to be Mr greater than or equal to 150 000 and Mr between 55 000 and 100 000.
Chromatography, Gel↗
Drug permeation through human skin II: Permeability of ionizable compounds.
The aim of this study was to establish whether ionized as well as un-ionized forms of certain 4-oxo-4H-1-benzopyran-2-carboxylic acids (chromone-2-carboxylic acids) with pKa values less than 2 permeated through excised human skin and, if so, to determine the permeability coefficients of the permeating species. The permeation properties of four carboxylic acids were studied as a function of concentration over the pH range 5-7 at 37 degrees C with plexiglass diffusion cells. Plots of J/CA- (the total flux due to un-ionized and ionized species obtained under steady-state conditions per unit concentration of ionized drug in the donor compartment) against CH3O+ resulted in straight-line relationships. The intercepts of these plots were shown to equal PA-, whereas the slopes multiplied by the Ka values of the compounds equalled PHA, the permeability coefficients of the ionized and un-ionized species, respectively. With all four compounds, both species were found to permeate skin, although the permeability coefficients of the un-ionized species were approximately 10(4) greater than those for the ionized species. It was demonstrated that the relative contributions of the ionized and un-ionized species to the total flux, as well as the total flux, vary significantly, depending on the pH of the drug solution in the donor cell. This may provide a means of controlling the flux of these and similar compounds through human skin.
Chromatography, High Pressure Liquid↗
Subcellular localization of enzymes involved in leukotriene formation within human polymorphonuclear granulocytes.
The subcellular localization of enzymes involved in leukotriene formation was analysed according to biological (chemotaxis, spasmogenic properties) and analytical methods. By subcellular fractionation the major activity for 5--lipoxygenase and L-gamma-glutamyltranspeptidase coeluted with the 200,000 g precipitate while glutathione-S-transferase activity was mainly present in the 200,000 g supernatant. Our data were supported by results indicating that the 200,000 g precipitate and supernatant fractions proved to be most active in generating 5-HETE and leukotriene C4 (LTC4) respectively. The 200,000 g pellet was the most active fraction in transforming synthetic LTC4 into LTD4 and LTE4. When synthetic LTD4 was incubated with the various subcellular fractions and the appearance of LTE4 was analysed the 20,000 and 200,000 g pellets were the most potent fractions. Several discrepancies observed using biological, biochemical and analytical (synthetic substrates) methods may be in part due to the formation of leukotriene isomers which interfere with the biological assays.
Chemotactic Factors↗
[The role of mast cells in allergic and inflammatory diseases].
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Chemotaxis, Leukocyte↗
Generation of leukotrienes and lipoxygenase factors from human polymorphonuclear granulocytes during bacterial phagocytosis and interaction with bacterial exotoxins.
The generation and release of lipoxygenase factors and leukotrienes from human polymorphonuclear granulocytes is demonstrated during bacterial phagocytosis and interaction with bacterial exotoxins (alpha-toxin, enterotoxin, lipase from Staph. aureus; Streptolysin O; cytotoxin from Pseudomonas aeruginosa). The leukotrienes released during stimulation exert chemotactic properties for human neutrophils and guinea pig eosinophils (leukotriene B4) and show the characteristic profile of slow reacting substance activity which is induced by leukotriene C4, D4 and E4. The toxin induced spasmogenic activity obtained from human PMNs was inhibited in the presence of the SRS-antagonist FPL 55712. The generation of lipoxygenase factors is also demonstrated by autoradiography using 14C arachidonic acid prelabelled granulocytes.
Animals↗
Drug permeation through human skin: I. Effect of storage conditions of skin.
The purpose of this study was to establish conditions for the preparation and storage of excised human skin such that it most closely retained the permeation characteristics seen with skin samples studied immediately after having been removed from cadavers. Using skin taken from the inner thighs of cadavers within 48 hr post mortem, we have compared drug permeation through samples that were used immediately following removal with samples that had been stored in either the frozen or dried state. With the chromone acid under investigation, it was found that samples of stratum corneum attached to the underlying epidermis used without prior storage consistently showed less permeation than samples taken from the same individual that had been frozen at -17 degrees C upon removal and then thawed before permeation studies were started. However, drug permeation through samples of stratum corneum plus epidermis that had been allowed to dry under controlled humidity conditions at room temperature were found to be similar to those obtained with fresh skin. These results indicate that dried skin, when appropriately rehydrated before use, exhibits rates of drug permeation similar to those found with fresh skin. With the chromone acids under investigation, the use of frozen samples of excised skin should be avoided since the extent of permeation exceeds that obtained with fresh skin samples.
Adult↗