Microenviromental investigation of polymer-bound fluorescent chelator by fluorescence microscopy and optical spectroscopy.

8-Hydroxyquinoline-5-sulfonic acid (HQS) was immobilized onto a strong-base anion-exchange resin AG MP-1 for the purpose of microenvironment investigation, resin characterization, and possibly sensing cadmium. The maximum loading of HQS was found to be 0.9340 mmol/g of AG MP-1. A plateau for Cd complex capacity was already obtained for 0.5500 mmol of HQS/g of AG MP-1. A minicolumn experiment showed an influence of influent Cd concentration on column capacity. IR and Raman spectra proved an electrostatic mode for HQS immobilization and Cd complex formation. UV spectroscopy showed significant differences between solution and solid state for both HQS and Cd complex. A fluorescence microscopy technique was used for fluorescence spectral measurement, microdistribution imaging, and study of photobleaching of HQS and the HQS-Cd complex in the resin phase. The fluorescence of immobilized HQS was found to be red-shifted with regard to the solid-state HQS. The microdistribution of uncomplexed and Cd-complexed AG MP-1-HQS was directly visualized by fluorescence imaging, showing a nonuniform distribution. Cadmium complexation modifies the fluorescence emission of uncomplexed AG MP-1-HQS, exhibiting an increased and red-shifted emission. Significant photobleaching of the fluorescence from the Cd complex was recorded, indicating the occurrence of photochemical reactions within the microenvironment of the resin phase.

Design and synthesis of 2-methyl-2-[4-(2-[5-methyl-2-aryloxazol-4-yl]ethoxy)phenoxy]propionic acids: a new class of dual PPARalpha/gamma agonists.

Propionic acid derivative 8, which was designed and synthesized based on putative pharmacophores of known PPARgamma- and PPARalpha-selective compounds, exhibits potent dual PPARalpha/gamma agonist activity as demonstrated by in vitro binding and dose overlap in the newly introduced EOB mouse model for glucose lowering and lipid/cholesterol homeostasis.

Uranyl-selective electrode based on a new bifunctional derivative combining the synergistic properties of phosphine oxide and ester of phosphoric acid

Ion-selective electrodes based on the bifunctional chelating agent O-methyldihexylphosphine oxide O'-hexyl-2-ethylphosphoric acid (HL) incorporated into a poly(vinyl chloride) membrane were developed. This new derivative is proposed as a single molecular unit combining the overall properties of the synergistic single components, di-2-ethylhexylphosphoric acid and trioctylphosphine oxide. Two different ionophores, HL and its uranyl complex (UO2L2), were studied. The response of the electrodes to uranyl ion was Nernstian for UO2L2 and super-Nernstian for HL ionophores, with detection limits of 3.0 x 10(-6) and 2.0 x 10(-5) M, respectively. Results indicate a more effective interaction with the analyte in the case of having a unique molecule incorporating the two functional groups immobilized into a polymeric membrane, rather than the separated two synergistic ligands. Flow-through tubular electrodes based on both ionophores were also used as potentiometric detectors in flow injection techniques.

The release of cytotoxic drugs from acrylic bone cement.

The ability of cis-platinum, 5-fluorouracil, and methotrexate to leach out from various types of bone cements was examined in three different experimental systems: (1) in vitro release in physiological solution; (2) in vitro release in the presence of mouse fibrosarcoma cells; and (3) in vivo release in rabbits. The amount of drugs released was measured either spectrophotometrically by atomic absorption or by using tritium-labeled drugs. In vitro cement pellets were found to release these drugs slowly for up to six months; release was greater in the first few days, rapidly declining with time. Up to 6% of the methotrexate implanted leached out during the entire experiment. The figures for cis-platinum and 5-fluorouracil were much less: 3.3% and 3.4%, respectively. Palacos bone cement had the best leaching properties. The drugs leached out were also effective in reducing the numbers of viable mouse fibrosarcoma cells in tissue culture. In vivo, high levels of the drugs were recovered from blood drained from the operative wound of the rabbits, while very low levels of these drugs were found in the serum. Anticancer drug-loaded cement may be used effectively in the treatment of pathologic fractures and tumor surgery. This delivery method may reduce the side effects that result from systemic administration of such drugs.

Anti-proliferative effects and phenotypic alterations induced by 8-hydroxyquinoline in melanoma cell lines.

The effect of the transition metal chelator, 8-hydroxyquinoline (8-HQ), was examined on the growth and phenotype expression of B16 mouse melanoma cells. Micromolar concentrations of 8-HQ inhibited the growth of B16 cells as well as human melanoma cell lines. Removal of 8-HQ from the culture medium restored normal cell growth. Growth inhibition by 8-HQ was accompanied by phenotypic alterations that included changes in cell morphology, increased production of melanin and enhanced activities of the enzymes gamma-glutamyl transpeptidase and NADPH cytochrome c reductase. These changes might be associated with a better differentiated phenotype.

Facile thiolytic removal of the o-nitrophenylsulphenyl amino-protecting group.

2-Mercaptopyridine was used to effect the selective, mild and efficient cleavage of the o-nitrophenylsulphenyl amino-protecting group from several amino acids and peptides. By utilization of this reagent a stepwise synthesis of the tetrapeptide Thr-Lys-Leu-Arg([Leu3]tuftsin) was successfully achieved. The potential use of 2-mercaptopyridine in mechanized peptide synthesis via the polymeric reagents approach is discussed.

Urographic visualization of multicystic kidneys.

Classically, multicystic kidneys have been described as having no functioning renal parenchyma that, consequently, should not be seen on excretory urography. However, during the last several years, sufficient concentration of contrast medium permitted radiographic visualization of renal tissue in 4 cases of pathologically typical multicystic kidneys.

New useful reagents for peptide synthesis. Insoluble active esters of polystyrene-bound 1-hydroxybenzotriazole.

Insoluble 1-hydroxbenzotriazole-bound polystyrene was prepared through a series of chemical modifications of commercially available polystyrene. Reaction of 3-nitro-4-chlorobenzyl alcohol or of 3-nitro-4-chlorobenzyl bromide with polystyrene in the presence of aluminium trichloride yielded (3-nitro-4-chloro)benzylated polystyrene. Upon reaction with hydrazine it was converted to (3-nitro-4-hydrazine) benzylated polystyrene which was cyclized, by acidolysis, to yield 1-hydroxybenzotriazole-bound polystyrene. This was coupled, using N, N' -dicyclohexylcarbodiimide as the coupling agent, to many N-blocked amino acid derivatives, yielding polymeric polystyrene-bound active esters. Such derivatives are highly reactive and their efficacy in the synthesis of several peptides, including that of the tetrapeptide Boc-L-Leu-L-leu-L-Val-0bzl-L-Tyr-0Bzl and of thyrotropin-releasing hormone was demonstrated.

The gravity suit: a useful device in complicated urologic hemorrhage.

External counterpressure with a gravity suit was used to control intractable postoperative bleeding in 4 urologic patients. Two patients had coagulation defects, and 2 had been unsuccessfully reexplored prior to application of the G-suit. The bleeding was controlled with preservation and restoration of vital signs in each case. In 3 cases external counterpressure may have been lifesaving.

Bilateral renal aspergillosis.

The recent increased use of steriods, immunosuppressive agents and cytotoxic drugs has been associated with a rise in the incidence of significant fungal disease. The first case of bilateral renal aspergillosis without disseminated involvement is reported. A multitherapeutic approach, including surgical evacuation of masses of hyphae, parenteral antimycotic chemotherapy and topical instillations of amphotericin B, were necessary to clear the kidneys. Newer systemic agents such as 5-fluorocytosine and rifampicin were also used. Treatment of fungal infections of the urinary tract is discussed.

Polystyrenes impregnated with ethers-A polymeric reagent selective for gold.

A polymeric reagent selective for gold was obtained by impregnating XAD-2 polymeric absorbant with ethylene diglycol dibutyl ether, a gold-selective liquid. The reagent showed a high selectivity for gold over the platinum group metals, nickel(II) and copper(II), but the selectivity relative to iron(III) was pH-dependent.

Polystyrene impregnated with beta-diphenylglyoxime, a selective reagent for palladium.

alpha- and beta-diphenylglyoximes impregnated on macroreticular polystyrene (XAD-2) were tested as adsorptive reagents and one of them (the beta-isomer) was found to adsorb palladium in preference to platinum (selectivity factor 20) and nickel (factor > 100).