Changes in intrahepatic portal hemodynamic in early stage hepatic abscesses

Color Doppler sonography was used to investigate the changes in intrahepatic portal hemodynamics in early stage hepatic abscesses (21 lesions). At time of patients' admission, 10 lesions measuring over 6 cm showed reverse flow from at least one of their corresponding segmental portal branches, but 11 lesions measuring 6 cm or less did not show this phenomenon. All portal branches with reverse flow eventually returned to a normal direction of flow after successful medication. In conclusion, a large early stage hepatic abscess may show temporary reverse portal flow on color imaging. Thus, a differential diagnosis of hepatic tumors with reverse portal flow should include early stage hepatic abscesses.     

Identification and characterization of a phase-variable nonfimbrial Salmonella typhimurium gene that alters O-antigen production

Salmonella typhimurium 798, which was isolated from a pig, is known to phase vary from a nonadhesive to an adhesive phenotype. Cells of the adhesive phenotype adhere to porcine enterocytes, are more readily phagocytized by porcine neutrophils and macrophages, and once phagocytized can survive intracellularly, while cells of the nonadhesive phenotype die rapidly. The effect of phenotypic switching also can be visualized by changes in colony morphologies and the presence of between 10 and 15 proteins in the envelopes of cells in the adhesive phenotype. Mutants previously constructed with cells in the adhesive phenotype and the transposon TnphoA were screened to identify mutants lacking one or more of the unique proteins. One mutation was cloned and sequenced, and the mutation was shown to be in rfaL (O-antigen ligase). Expression of O antigen was shown to be phase variable. The adhesive strain expressed an O antigen that was at least eightfold longer than that for the nonadhesive strain and by virtue of O-antigen production was resistant to porcine complement. The mutant survived intracellularly in phagocytic cells as well as its wild-type parent.     

Participation of cytochrome P450-2B and -2D isozymes in the demethylenation of methylenedioxymethamphetamine enantiomers by rats

The cytochrome P450 isozymes in rat liver microsomes that catalyze the demethylenation of methylenedioxymethamphetamine enantiomers to the corresponding dihydroxymethamphetamine were characterized. Dihydroxymethamphetamine formation in liver microsomes from male Sprague-Dawley rats exhibited multienzyme kinetics, with Km values in the micromolar/millimolar range. The stereoselectivity [(+)-isomer versus (-)-isomer] varied from 0.78 to 1.94 after pretreatment of the rats with phenobarbital, 3-methylcholanthrene, pregnenolone-16 alpha-carbonitrile, or pyrazole, suggesting that different isozymes participate in the reaction. The low-Km demethylenation was not induced by these compounds and was not inhibited by antibodies raised against CYP2C11. Liver microsomes from female Dark-Agouti rats, a strain genetically deficient in CYP2D1, exhibited demethylenation activities that were 9% of those in microsomes from male Sprague-Dawley rats. The low-Km demethylenation was also inhibited by CYP2D substrates such as sparteine, bufuralol, or desipramine and was almost completely inhibited by antibodies against P450 BTL, which belongs to the CYP2D family. The higg-Km demethylation activity was induced by phenobarbital and pregnenolone-16 alpha-carbonitrile and the activity in both untreated and phenobarbital-induced microsomes was suppressed by anti-CYP2B1 IgG. Experiments with IgG raised against cytochrome b5 suggested that the hemoprotein contributed to the low-Km activity but not the high-Km activity. These results indicate that cytochrome P450 isozymes belonging to the CYP2D subfamily catalyze demethylenation with low Km values and that the reaction occurring with high Km values is likely to be mediated by members of the CYP2B family, but with the possible participation of other phenobarbital-inducible isoforms.     

Capsaicin inhibits plasma membrane NADH oxidase and growth of human and mouse melanoma lines

Hormone- and growth factor-stimulated NADH oxidase of the mammalian plasma membrane is thought to be involved in the control of normal cell proliferation. The aim of this study was to determine the effect of the naturally occurring quinone analogue capsaicin (8-methyl-N-vanillyl-6-noneamide) on the NADH oxidase activity of plasma membranes and cell growth of human primary melanocytes, the A-375 and SK-MEL-28 human melanoma cell cultures. NADH oxidase activity was inhibited preferentially in the A-375 melanoma cells but not in the primary melanocytes, by capsaicin. Inhibition of growth and the NADH oxidase by capsaicin could be induced in resistant SK-MEL-28 melanoma cells by co-administration of capsaicin with t-butyl hydroperoxide, a mild oxidising agent. Death of the inhibited cells was accompanied by nuclear changes suggestive of apoptosis. With B16 mouse melanoma, capsaicin inhibited both the NADH oxidase activity and growth in culture. Growth of B16 melanoma, transplanted in C57BL/6 mice, was significantly inhibited by capsaicin injected directly into the tumour site when co-administered with t-butyl hydroperoxide. The findings correlate the inhibition of cell surface NADH oxidase activity with inhibition of growth and capsaicin-induced apoptosis, and also suggest that the extent of inhibition may relate to the oxidation state of the plasma membrane.     

A nonpeptidyl growth hormone secretagogue

A nonpeptidyl secretagogue for growth hormone of the structure 3-amino-3-methyl-N-(2,3,4,5-tetrahydro-2-oxo-1-([2'-(1H-tetrazol-5 -yl) (1,1'-biphenyl)-4-yl]methyl)-1H-1-benzazepin-3(R)-yl)-butanamid e (L-692,429) has been identified. L-692,429 synergizes with the natural growth hormone secretagogue growth hormone-releasing hormone and acts through an alternative signal transduction pathway. The mechanism of action of L-692,429 and studies with peptidyl and nonpeptidyl antagonists suggest that this molecule is a mimic of the growth hormone-releasing hexapeptide His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 (GHRP-6). L-692,429 is an example of a nonpeptidyl specific secretagogue for growth hormone.     

Diminished heparin binding of a basic fibroblast growth factor mutant is associated with reduced receptor binding, mitogenesis, plasminogen activator induction, and in vitro angiogenesis

Using modeling of heparin-fibroblast growth factor interactions, we replaced four basic residues of basic fibroblast growth factor (FGF-2) with neutral glutamine residues by site-specific mutagenesis to give the mutants K128Q, K138Q, K128Q-K138Q, R129Q, K134Q, and R129Q-K134Q. The FGF mutants were characterized for their receptor and heparin binding affinities, mitogenic and cell proliferation activities, and their ability to induce plasminogen activator (PA) production and in vitro angiogenesis by cultured endothelial cells. Heparin binding properties and biological activities of the three mutants involving R129 and K134 remained essentially unchanged; however, significant changes for three mutants involving K128 and K138 were found. The KD values for heparin binding for K128Q and K138Q mutants were increased about 10-fold, and that for the K128Q-K138Q double mutant was increased by about 100-fold. The mutant K128Q-K138Q required a 10-fold higher concentration of heparin to promote binding to heparan sulfate proteoglycan (HSPG)-deficient CHO cells transfected with fibroblast growth factor receptor-1 (FGFR1) or to induce DNA synthesis in HSPG-deficient myeloid cells transfected with FGFR1. Binding affinities of the mutants to cell surface receptors on BHK-21 cells, however, were similar to that of wild-type FGF-2. In endothelial cell proliferation assays the activities of K128Q and K128Q-K138Q were about 10-fold lower than that of the wild-type protein, whereas the K138Q mutant exhibited wild-type activity. In addition, the K128Q-K138Q mutant displayed a markedly lowered capacity to induce PA activity in cultured endothelial cells and to form capillary-like structures in an in vitro angiogenesis model.(ABSTRACT TRUNCATED AT 250 WORDS)     

Rapid arrest of seizures with an inhalation aerosol containing diazepam

Diazepam (DZP) and a mixture of Chinese herbs customarily used to treat epilepsy were prepared as an aerosol under the trade name Aerosolum Diaiepami Compositae or Flvalscop (FVS). FVS was studied in a single-blind trial in 101 patients with seizures preceded by an aura and in 19 without an aura to whom was administered by another person. FVS or a control preparation was administered. In 16-22 s, (average 18.5 s), the aura was interrupted and no seizure ensued in 90% of the cases treated with FVS and in 26% of cases treated with the control preparation. Of the 120 patients, 8 had elementary partial seizures with Jacksonian march, 18 had complex partial seizures (CPS), 7 had simple partial seizures with autonomic symptoms, and 87 had secondarily generalized tonic-clonic seizures. Eleven patients have now received FVS for 2 years (400 ml each). Forty patients for 1 year (150-200 ml each); none of these patients have shown any side effects or abnormal laboratory findings. An aerosol-administered drug may be a valuable adjunct to the antiepileptic drug (AED) arsenal and merits more extensive evaluation.     

Effect of Salt Concentration on Quality of Restructured Pork Chops

Restructured pork chops containing approximately 15% fat were manufactured from fresh hams and boston butts taken from sows. The effects of salt level (0%, 0.5%, 1.0%, and 1.5%) and freezer storage time (0 and 30 days) on quality attributes of restructured pork chops were studied with three replications. Triangle test differences were significant for all comparisons except 1.0% and 1.5% salt groups stored for 30 days. 2-Thiobarbituric acid (TBA) values increased linearly with increasing salt levels for both 0 and 30 days storage. Salt addition also linearly increased Instron slicing strength values, and improved flavor, juiciness, and textural properties. The addition of salt decreased raw color evaluations, Instron shearing values and cooking losses. Following 30 days freezer storage, treatments containing salt had higher TBA values and lower color scores than the control treatment containing 0% salt. Salt addition at levels between 0.5 and 1.0% is recommended for restructured pork chops.