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Biomedical subjects

R F Novak

Publications and source records attributed to R F Novak.

At least 109 records · Page 6Linked to original sources
PubMed1972

Barbiturate interaction with phosphatidylcholine.

A hydrogen-bonding interaction between phenobarbital or pentobarbital with phosphatidylcholine in chloroform is indicated by the effects of added phosphatidylcholine on the infrared and proton magnetic resonance spectra of these barbiturates. The nitrogenbound proton of the barbiturate and the orthophosphate moiety of the phosphatidylcholine molecule appear to be involved. The more pronounced effect with the two barbiturates occurs in the proton magnetic resonance spectra of phenobarbital with increased amounts of phosphatidylcholine. A plot of the chemical shift of phenobarbital N-H against the concentration of phosphatidylcholine is linear and gives an extrapolated shift of 260 Hz (2.6 ppm) at 35 degrees C for a phosphatidylcholine-phenobarbital ratio of unity, pure 1:1 complex. It is suggested that the general depressant nature of barbiturates may be accounted for by their association in a similar fashion with a number of other phosphate-containing molecules.

Chemical Phenomena↗
PubMedDate not supplied

Differential effects of organic hydroperoxides and hydrogen peroxide on proteolysis in human erythrocytes.

The effects of tert-butyl hydroperoxide, cumene hydroperoxide, and hydrogen peroxide on proteolysis in human red blood cells have been examined. The organic hydroperoxides effectively stimulated the rate of protein degradation in red cells and in hemolysate; in contrast, H2O2 addition was without significant effect in either system. tert-Butyl hydroperoxide or cumene hydroperoxide (8 mM) increased the rate of protein degradation in red cells 2.3- and 4-fold, respectively, relative to control as monitored by tyrosine release. In hemolysate, tert-butyl hydroperoxide and cumene hydroperoxide, present at 8 mM, produced a 2- and 3-fold increase in the rate of protein degradation, respectively, as compared to controls. Hydroperoxide-stimulated proteolysis in red cells or in hemolysate was concentration-dependent and reached saturation at 8 mM hydroperoxide. The reaction was linear for 2 h after which a plateau was reached. In contrast to the results observed for the organic hydroperoxides, H2O2 (100 or 200 mM) addition either alone or in the presence of the catalase inhibitor 3-amino-1,2,4-triazole (50-200 mM), failed to stimulate proteolysis. N-Acetylcysteine (20 mM) and dimethylthiourea (50 mM) inhibited the rate of hydroperoxide-stimulated proteolysis in red cells by approximately 50 and approximately 35%, respectively, and in hemolysate by 25 and 40%, respectively. The hydroxyl radical scavengers methyl sulfoxide (50 mM) or dimethylfuran (50 mM), metal ion chelators, or spin traps failed to decrease significantly the rate of organic hydroperoxide stimulated proteolysis. In addition, inhibitors of the calpain/procalpain system in red cell or hemolysate incubations challenged by organic hydroperoxide were without significant effect on the rate of proteolysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗
PubMedDate not supplied

Kepone (chlordecone) disrupts adherens junctions in human breast epithelial cells cultured on matrigel.

Perturbations in cell-extracellular matrix (ECM) interactions are a consistent feature of mammary tumors and cells in culture. We have utilized MCF-10ATG3B human breast epithelial cells to examine whether the organochlorine Kepone induces alterations in cell adhesion molecules important to cell-cell and cell-ECM interactions. Kepone effects on the levels and association of proteins involved in adherens junctions or desmosomes were examined using immunoblot analysis and immunoprecipitation. MCF-10ATG3B cells cultured on an ECM of Matrigel form lattice-like structures that are disrupted with 0.1 and 1 microM Kepone. E-cadherin protein levels decreased significantly by approximately 23% and approximately 69% following treatment with 0.1 and 1.0 microM Kepone, respectively, relative to solvent-treated cells. Desmoglein and alpha- and gamma-catenin levels did not vary significantly with Kepone. Beta-catenin protein levels decreased significantly by approximately 37%, 36% and 53% at 0.01, 0.1 and 1.0 microM Kepone, respectively. E-cadherin-gamma-catenin association was disrupted with 0.1 and 1.0 microM Kepone. Thus, Kepone disrupts cellular architecture, specifically E-cadherin-gamma-catenin containing adherens junctions, which may ultimately affect cellular phenotype.

Adherens Junctions↗
PubMedDate not supplied

Oxidation of 1,1,1,2-tetrafluoroethane in rat liver microsomes is catalyzed primarily by cytochrome P-450IIE1.

1,1,1,2-Tetrafluoroethane (R-134a), a nonozone-depleting alternative air-conditioning refrigerant and propellant for pharmaceutical preparations, is oxidatively defluorinated by rat hepatic microsomes. In this report we show that induction of cytochrome P-450IIE1 in rats, by pyridine administration, resulted in an 8-fold increase in the rate of R-134a metabolism by hepatic microsomes (Vmax 47 vs. 6 nmol F-/mg microsomal protein/15 min). Furthermore, when data were normalized for P-450 content, a 4-fold increase in R-134a metabolism was noted for IIE1-enriched microsome preparations. In contrast, phenobarbital and Aroclor 1254 decreased the specific activity of hepatic microsomes for this function. The microsomal content of P-450IIE1, as evaluated by Western blot, was elevated significantly only in microsomes from pyridine-treated rats. p-Nitrophenol and aniline, which are metabolized at high rates by rat P-450IIE1, decreased the rate of R-134a defluorination by hepatic microsomes; Dixon plot analysis indicated competitive inhibition with a Ki of 36 microM p-nitrophenol or 115 microM aniline. Pyridine also potently induced defluorination of R-134a catalyzed by rabbit liver microsomes. Studies with individual P-450 isozymes purified from rabbit liver showed that the phenobarbital- and polycyclic hydrocarbon-induced isozymes (IIB1 and IA2) defluorinated R-134a at negligible rates (1.9 and 0.4 nmol F-/nmol P-450/60 min, respectively). In contrast, P-450IIE1 catalyzed defluorination of R-134a at a relatively high rate (16.2 nmol F-/nmol P-450/60 min); isozyme IA1, which also is induced by nitrogen-containing heterocycles such as pyridine, was somewhat active (5.3 nmol F-/nmol P-450/60 min).(ABSTRACT TRUNCATED AT 250 WORDS)

Aniline Compounds↗
PubMedDate not supplied

Effects of mitoxantrone and bisantrene on platelet aggregation and prostaglandin/thromboxane biosynthesis in vitro.

The effects of mitoxantrone and bisantrene on agonist-stimulated platelet aggregation, prostaglandin E2 and thromboxane B2 production were examined and results compared with those produced by indomethacin and acetylsalicylic acid. Both mitoxantrone and bisantrene effectively inhibited collagen-, ADP-, and epinephrine-stimulated platelet aggregation. Collagen (0.54 microgram/ml)-stimulated platelet aggregation was inhibited by 50% at 60 microM mitoxantrone and 8 microM bisantrene. The concentration of drug required for inhibition of platelet aggregation varied inversely with the level of collagen stimulus employed. Mitoxantrone and bisantrene inhibited both the first and second phase of epinephrine-stimulated platelet aggregation. Complete inhibition of the second wave of aggregation was obtained at greater than 160 microM mitoxantrone and 16 microM bisantrene. Mitoxantrone is comparable in potency to acetylsalicylic acid which inhibited the second wave of epinephrine-stimulated aggregation 50% at 160 microM, whereas bisantrene may be compared to indomethacin which produced complete inhibition of aggregation at 16 microM. Production of PGE2 and TXB2 in epinephrine-stimulated platelets was inhibited by both drugs with 50% inhibition of PGE2 production occurring at 12 microM mitoxantrone and 3 microM bisantrene. Thromboxane B2 production was inhibited by 50% at 10 microM mitoxantrone and 5 microM bisantrene. Indomethacin inhibited PGE2 and TXB2 production 50% at 4 microM. Thus mitoxantrone and bisantrene inhibit platelet aggregation and prostaglandin production which may be of significance in metastasis and in prostaglandin-mediated physiologic and immune responses.

Adult↗