Chemically Enhanced Convective Dissolution of CO_{2}.

Convective dissolution, one of the main mechanisms for geological storage of CO_{2}, occurs when supercritical or gas CO_{2} dissolves partially into an aqueous solution, thus triggering downward convection of the denser CO_{2}-enriched liquid. Chemical reaction in the liquid can greatly enhance the process. Here, experimental measurements of convective flow inside a cylinder filled with a sodium hydroxide (NaOH) solution show that the plume's velocity can be increased tenfold as compared to a situation with no NaOH. This tremendous effect is predicted by a model with no adjusting parameters.

Hydrodynamic fingering instability induced by a precipitation reaction.

We experimentally demonstrate that a precipitation reaction at the miscible interface between two reactive solutions can trigger a hydrodynamic instability due to the buildup of a locally adverse mobility gradient related to a decrease in permeability. The precipitate results from an A+B→C type of reaction when a solution containing one of the reactants is injected into a solution of the other reactant in a porous medium or a Hele-Shaw cell. Fingerlike precipitation patterns are observed upon displacement, the properties of which depend on whether A displaces B or vice versa. A mathematical modeling of the underlying mobility profile confirms that the instability originates from a local decrease in mobility driven by the localized precipitation. Nonlinear simulations of the related reaction-diffusion-convection model reproduce the properties of the instability observed experimentally. In particular, the simulations suggest that differences in diffusivity between A and B may contribute to the asymmetric characteristics of the fingering precipitation patterns.

Experimental evidence of reaction-driven miscible viscous fingering.

An experimental demonstration of reaction-driven viscous fingering developing when a more viscous solution of a reactant A displaces a less viscous miscible solution of another reactant B is presented. In the absence of reaction, such a displacement of one fluid by another less mobile one is classically stable. However, a simple A+B→C reaction can destabilize this interface if the product C is either more or less viscous than both reactant solutions. Using the pH dependence of the viscosity of some polymer solutions, we provide experimental evidence of both scenarios. We demonstrate quantitatively that reactive viscous fingering results from the buildup in time of nonmonotonic viscosity profiles with patterns behind or ahead of the reaction zone, depending on whether the product is more or less viscous than the reactants. The experimental findings are backed up by numerical simulations.

Anti-hyperlipidemic and anti-atherosclerotic actions of shosaikoto (kampo medicine).

We investigated the anti-atherosclerotic action shown by Shosaikoto, a Kampo medicine, using hypercholesterolemic mice. Oral administration of Shosaikoto significantly suppressed the elevation of serum cholesterol in C57BL/6 mice fed a 1.25% cholesterol-enriched diet for four weeks and improved the T cell ratio in peripheral blood, which decreased with the increase of the serum cholesterol level. In addition, Shosaikoto reduced the accumulation of cholesteryl oleate, which alters macrophages into foam cells, after the treatment of macrophages with oxidized or acetylated low density lipoprotein (LDL). Enzymatic study revealed that the treatment of macrophages with oxidized LDL enhanced acyl-coenzyme A: cholesterol acyltransferase (ACAT) activity and markedly reduced neutral cholesteryl ester hydrolase (NCEase) activity. Shosaikoto treatment prevented a decrease in the NCEase activity, however due to the oxidized LDL treatment, although it slightly augmented ACAT activity. Thus, Shosaikoto, which is known to modulate the immune system, improves macrophage and lymphocyte functions diminished by hypercholesterolemia, resulting in an anti-atherosclerotic action.

Relation between monocytes in peripheral blood and development of atherosclerosis in hypercholesterolemic rabbits.

The relation among circulating monocytes, serum cholesterol and LDL cholesterol in manifestation of atherosclerosis was investigated in hypercholesterolemic rabbits. Serum cholesterol increased sharply and reached a plateau at 12 weeks after the start of cholesterol diet feeding; LDL cholesterol gradually increased until 24 weeks, and the number of monocytes in blood started to decrease abruptly around 12 weeks and resulted in less than 1% total white blood cells at 24 weeks, as reflected by a severe progression of atheroma formation. This result indicated that the decrement of monocyte number in blood was predictive of the presence of severe atherosclerotic plaques.

Effects of Shosaikoto (kampo medicine) on lipid metabolism in macrophages.

We investigated effects of Shosaikoto treatment on cholesterol metabolism in macrophages. Although macrophages, harvested from mice treated with Shosaikoto, took up a small amount of control low density lipoprotein (LDL) (thiobarbituric acid-reactive substance (TBA-RS) value was 0.27 pmol/mg of protein) as control macrophages, they took up more LDL modified with CuSO4 (TBA-RS value was 6.12 pmol/mg of protein) than control macrophages. Degradation of both control LDL and oxidized LDL was enhanced in Shosaikoto treated macrophages. In the presence of control LDL or in the absence of LDL, incorporation of [3H]oleic acid into chlesteryl oleate was significantly reduced in Shosaikoto treated macrophages. This suggests that acyl-coenzyme A:cholesterol acyltransferase (ACAT) activity in macrophages was partly inhibited by Shosaikoto treatment. On the other hand, in the present of oxidized LDL, cholesteryl ester accumulated in Shosaikoto treated macrophages as much as in controls. However, cholesteryl oleate efflux from macrophages in the presence of high density lipoprotein (HDL) was enhanced in Shosaikoto treated macrophages. These result indicate that Shosaikoto facilitates oxidized LDL catabolism in macrophages, resulting in the augmentation of oxidized LDL uptake and the elimination of cholesterol from macrophages by HDL. These Shosaikoto effects may prevent foam cell formation and the progression of atherosclerotic lesions.

Metabolism and penetration through blood-brain barrier of parkinsonism-related compounds. 1,2,3,4-Tetrahydroisoquinoline and 1-methyl-1,2,3,4-tetrahydroisoquinoline.

14C-Labeled 1,2,3,4-tetrahydroisoquinoline (TIQ) and 1-methyl-1,2,3,4-tetrahydroisoquinoline (1MeTIQ) were synthesized, and their metabolism and tissue distribution were studied. Both compounds showed similar metabolic patterns. In 24 hr after po administration (50 mg/kg) to rats, 76% of TIQ and 72% of 1MeTIQ were excreted unchanged, and 2.7 and 8.7% were excreted as the 4-hydroxyl derivatives, 4-hydroxy-TIQ and 4-hydroxy-1MeTIQ, respectively. Small amounts of N-methylated metabolites, 2-methyl-TIQ (0.4%) and 2-methyl-1MeTIQ (0.7%) were detected. Isoquinoline (2.5%) also was found as a metabolite of TIQ and 1-methyl-3,4-dihydroisoquinoline (1.0%) was found as a metabolite of 1MeTIQ. The concentration of labeled compounds in the brain was about 4.5-fold higher than the blood concentration at 4 hr after dosing, and over 90% was unchanged TIQ or 1MeTIQ. These data indicated that TIQ and 1MeTIQ easily passed through the blood-brain barrier and were concentrated in the brain. Thus, it appears that TIQ and 1MeTIQ as endogenous or exogenous amines may accumulate in the brain and may be related to the onset of Parkinson's disease.

Application of chemical P-450 model systems to study drug metabolism. III. Metabolism of 3-isobutyryl-2-isopropylpyrazolo[1,5-alpha]pyridine.

Oxidation of 3-isobutyryl-2-isopropylpyrazolo[1,5-alpha]pyridine (IBPP) was carried out with various chemical model systems for cytochrome P-450 in comparison with the liver microsomal system of rats or humans. Alpha-hydroxylation of side chains and ring hydroxylation at the 6 and 7 positions were the main reactions in both systems. A pattern analysis of products using two dimensional thin layer chromatography was employed to compare the functions of the chemical model systems with those of microsomal systems. The reaction profile of IBPP by the catalyst/Pt-colloid/H2, O2 system was most similar to that of human or rat microsomal system. The utility of these chemical models is discussed from the viewpoint of drug metabolism.

Response of liver to glucocorticoid is altered by administration of shosaikoto (kampo medicine).

The effects of Shosaikoto, one of the Kampo medicines used for therapy for chronic hepatitis, on liver functions were studied in mice. Oral administration of Shosaikoto for 5 d enhanced the well-known induction of tyrosine aminotransferase (TAT) activity by dexamethasone. Further, TAT activity in mice treated with Shosaikoto was induced effectively by a smaller dose of dexamethasone, as compared with that in control mice. However, Shosaikoto itself did not induce TAT activity in the liver on oral administration or in cultured hepatocytes by direct addition. Moreover, Shosaikoto did not affect the induction of TAT activity by butyryl-adenosine 3',5'-cyclic monophosphate. The amplifying effect of Shosaikoto seemed to be specific for induction by dexamethasone. These data suggest that Shosaikoto makes the liver sensitive to glucocorticoid by some unknown mechanism.

Modification of macrophage functions by Shosaikoto (kampo medicine) leads to enhancement of immune response.

The effects of Shosaikoto, one of the Kampo medicines, on macrophage functions were studied in mice. Oral administration of Shosaikoto (1.2 g/kg of body weight) increased the change of the membrane fluidity of macrophages and diminished prostaglandin E2 production. Moreover, macrophages from mice orally given Shosaikoto phagocytized antigen more efficiently than control macrophages, resulting in presentation of much more antigen to lymphocytes. These results suggest that Shosaikoto enhances the immune response through at least two different routes, that is, through eliminating the inhibition of lymphocyte functions by prostaglandin E2 and through presenting antigen more efficiently.