Gas chromoatography with flame ionization detector (FID) along with mass spectrometry (GC/MS) were used for the screening and quantification of methamphetamine (MA) and its major metabolite, amphetamine (AM0, in blood and urine in eleven fatal cases in which MA abuse was suspected. Postmortem blood MA varied from $0.5-30.2\;\mu{g/ml}$, while Am levels ranged from none detected (6 of 11 cases) to 4.8 .mu.g/ml. Additionally, distribution studies were performed in three of these cases in which tissue smaples were available for evaluation. Liver contained the highest ocncentration of MA among the tissu samples. In eight of the eleven cases, when no other direct cause of death was evident (i.e. 3 cases of traumatic dath0, either no blood AM was found or the ratio of MA/AM was 3.4 or greater. These data are consistent with acute MA use followed by death due to acute drug intoxication or by the occurrence of hypersensitivity and reverse seen in cases of chronic drug abuse.

The acid dissociation constants of certain Schiff bases derived from isatin with p-substituted benzoyl hydrazines and somee amino acids of glycine, $\beta$-and $\alpha$-alanine, valine, $\beta$-phenyl-$\alpha$-alanine and anthranilic acid have been detemined potentiometrically at different temperatures in different aquo-organic solvent mixtures (ethnol, dioxane, dimethyl formamide, methanol, acetone and tetrahydrofurance). The pKa values were demonstrated on the light of the different electornic and steric effects of the substituents and the sovlent characteristics. In all the mixed media used, ionization of the compounds decreased by increasing the mole fraction of the organic cosolvent. Theemodynamic parameters $(\Delta{H}^\circ,\;\Delta{G}^\circ,\;\Delta{S}^\circ)$ were evaluated. The structural effects of the investigated compounds on these parameters were reported and discussed.

Two series of substituted sulforrythiazolidin-4-ones and sulforrylthiazolines have been synthesized and examined for their antidiabetic and biological aticity.

We investigated the effects of n-alkanols on the range and rate of the lateral diffusion of 1, 3-di(1-pyrenyl)propane in the model membranes of total phospholipid fraction extracted from synaptosomal plasma membrane vesicles. n-Akanols increased the range and rate of the lateral diffusion of 1, 3-di(1-pyrenyl)propane in the bulk model membrane structures (inner + outer monolayers) and the potencies of n-alknols up to 1-nonanol increased by 1 order of magnitude as the carbon chain length increases by two carbon atoms. The cut-off phenomenon was reached at 1-decanol, where further icnrease in hydrocarbon length resulted in a decrease in the lateral diffusion. However, significant changes in the 1'/1 value were not observed by methanol (from 100 to 2500 mM), ethanol (from 25 to 800 mM), and 1-propanol (from 10 to 250 mM) over entire concentration.

Flavonol derivatives were tested for their anticlastogenic effect against induction of micronuclei by n-methyl-n'-nitor-n-nitorsoguanidine(MNNG), and against induction of chromosome aberration by bleomycin or MNNG.belomycin. For micronudeus assay, each flavonol derivative (0, 0.001, 0.01, 0.1, 1, 10 and 100 mg/kg) was administered orally twice with 24 h interval, together with intraperitioneally administered MNNG(150 mg/kg). The result showed that msot flavonol derivatives tested were effective in suppresing the frequencies of micronude induced by MNNG. For chromosome aberration assy, each flavonol derivative (0, 0.1, 1, 10m and 100 mg/kg)was administered to mice orally in vivo, and then mice were sacrificed and spleen lymphocyte cultures were made. Bleomycin $(3\;\mu$g/ml) was treated to the mouse spleen hymphocyte cultures at 24 h after con A initiation. There wre nomarked decrease tendencies in chromosome aberration unless all doses of galangin and some doses of several flavonol derivatives tested. In the another experiment, we have evaluated the effect of flavonol derivatives on the enhancement of bleomycin-induced chromsome aberration by MNNG. Most of flavonol derivtives reduced the incidence of chromosome aberration induced by in vitro treatment of bleomycin followed by in vivo treatment of MNNG. Galangin particulary showed a dose-dependent decrease tendency. Other flavonol derivative showed slightly suggest that most of flavonol derivatives may be capable of protecting the inhibition of suggest that most of flavonol derivatives may be capable of protecting the inhibition of DNA-repair by MNNG. Our data indicate clearly that flavonol derivatives can suppress MNNG-induced genotoxicity such as an induction of MNPCEs. Therfore, our results could suggest that flavonol derivtives may be useful as a chemopreventive agent of MNNG.

($\pm$)-Myodesmone was synthesized, starting from 2-cyclopentenone. The key reaction involved $\alpha$-dimethoxymethylation of 2-cyclopentenone and organocopper conjugate addition reaction.

The anti-coagulant activity of ilexoside D isolated from the roots of ilex pubescens Hook. et Am. was investigated in in vivo models of blood coagulation in rats. On oral administration, ilexoside D prolonged the bleeding time and the whole blood recalcified clotting time, but not the plasma recalcified clotting time. In vitor, ilexoside D did not affect the recalciffed clotting times of whole blood, platelet-rich plasma(PRP), and platelet-poor plasma(PPP), while in the presence of tissue factor the compound prologed the reduced proth-rombin times of whole blood, PRP and PPP in the dose-dependent manner. These results indicate that ilexoside D has the anit-tissue factor activity as well as the antithromobotic activity.

($\pm$)-Higenamine is known as a cardiotonic principle of aconite root (root of Aconitum spp., Ranunculaceae). A simple and sensitive detection method for higenamine was developed by using gas chromatography-mass spectrometry (GC/MS). The recovery of higenamine after extraction and concentration with XAD-2 resin column was around 95% from rat biological fluids such as bile, plasma and urine. The limits of detection of higenamine in these biological fluids were approximately 0.1 ng/ml each. It has well been suggested that tetrahydroisoquinolines possessing catechol moiety such as higenamine should be subjected to the catechol-O-methyl transferase (COMT) activity in vivo. We detected two major peaks of presumed metabolites of higenamine in the total ion chromatogram obtained from the rat urine sample after the oral adminstration of ($\pm$)-higenamine. The scan mass spectrum of one of the metabolties coincided with those obtained from coclaurine $(C_6$-O-methyl higenamine) and those of the other metabolite are suggestive of isococlaurine $(C_7$-O-methyl higenamine).

For the analysis of structure relationship of ar-turmerone analogues, the compounds containing the various substituents on the phenyl ring and 1(or 2)-naphthyl group in the place of phenyl of ar-turmerone were prepared and tested their cytotoxicity against HL-60, K-562, and L1210 leukemia cells in vitro. The substituents at para position are methoxy, phenoxy, methyl, trifluoromethyl, fluoro, and chloro. At meta position methoxy, methyl, trifluoromethyl, or chloro groups at ortho position mathoxy or chloro group were introduced. Against HL-60 and K-562 cells, $ED_{50}$ values of the analogues are ranged from 0.8 to $30.0\;\mu{g/ml}$. Againste L1210 cell, these are located more than $20.0\;\mu{g/ml}$. However, 5-carbone-thoxy-2-methyl-6(1-naphthyl)-2-octen-4-one (5n)possesses $ED_{50}$ valuses 0.8, 2.1, $6.5\;\mu{g/ml}$ against HL-60, L1210 cells, respectively. The electronic nature of the substituents on phenyl ring of ar-tumerone dose not affect the biological activity. Therefore the flat structure of aromatic potion of ar-tumerone analogues is the more important factor for their activity rather than its electronic nature. The potentiation of the cytotoxicity with the enlargement of aromatic ring region also supports the importance of the plane structure of this area. The restriction of the single bond rotation between C-6 and aromatic ring through the introduction of substituents at the ortho position of phenyl ring and the increment of size of alkyl group at C-6 position enhances the activity. Therefore the effective conformation should by the one having the orthogonal arrangement between the aromatic ring and the side chain.

A new device to detect methamphetamine (MA), amphetamine(A) and its metabolites in urine was developed using the paper strip method and the test tube method of dry chemical reagents. The reagent containing tetrabromophenolphthalein ethyl ester (TBPE) and borax. For the TBPE paper strip method, a device was prepared with a window at each end of the reagent paper strip ; one window is for the sample application, and the other window is for the methylene chloride. The diffused sample from one window reacts with reagent in the paper and produces color at the point where it meets with methylene chloride which has diffused form the other side. A positive smaple produces as red-purple color and the negative sample a greenish color, with a detection limit of 5-10 ppm. The result can be obtained within one minute. For the TBPE test tube method which contains dry reagents, the detection limit is 5 ppm and the result can be obtaineed within 30 seconds, however the carry-on is not as convenient as the paper strip method. The performance of both methods were evlauated by comparing with the results of gas chromatography (GC) and fluorescence polarizaiton immunoassay (FPIA). The results were proven that both methods were useful as primary screening reagents to detect MA in urine and in dry powder.

Gly-224 residue of yeast alcohol dehydrogenase was mutated by site-directed mufagenesis to isoleucine, which is the corresponding amino acid residue of horse liver alcohol dehydrogenase. The mutated gene on M13 vector was subcloned in YEp13 and used to transform Saccharomyces cerevisiae 302-21 #2 strain, and the expressed protein was purified. The tumover numbers of mutant enzyme for ethanol and acetaldehyde were decreased copared to wild-type enzyme. The results of product inhibition studies indicated that the reaction mechanism was changed to Iso Theorell-Chance from Ordered Bi Bi. We supposed that Gly-224 was related to the enzyme reaction mechanism.

These studies were performed to investigate the acting sites of ginseng total saponins (GTS) on the U-50, 488H-induced antinociception and the inhibitory effect of the development of tolerance to U-50, 488H-induced antinociception by GTS were studied. The U-50, 488H-induced antinociception was ntagonized in mice pretreated with GTS intraperitoneally, intracerebrally. These antagonisms were reversed by the pretratment iwth a serotonin precursor, 5-hydroxytrypophan (5-HTP), but not with a noradrenaline precursor, L-dihydroxyphenylalanine (L-DOPA). However, the intraplantar sites. On the other hand, GTS inhibited the development of tolerance to U-50, 488H-induced antinociception was reversed by pretreatment with 5-HTP, but not with L-DOPA. Therefore, the antagonism of U-50, 488H-induced antinociception and the inhibition of the development of tolerance to U-50, 488H-induced antinociception and the inhibition of the development of tolerance to U-50, 488H-induced antinociception by GTS are dependent on serotonegic mechanisms.

Calli and suspension cultures were obtained following inoculation of the explant from leaves of Ginkgo biloba L on the supplemented MS basal medium. The obtained calli and suspension cultured cells were able to produce detectable amounts of ginkgolides which are known as natural specific PAF antagonists. The production of ginkgolides in the calli and suspension cultured celles were identified using GC/MS, GC and HPLC with authentic ocmpounds. Since the production of ginkgolides A and B the calli and suspension cultured cells had been confirmed, effects of types and concentration of plant growth regulators, media and illumination on the induction and growth of the callus were studied. The concentrations of growth regulators for optimal callus were studied. The concentrations of growth regulators for optimal callus induction were studied. The concentrations of growth regulators for optimal callus induction were 1.0 to 2.0 mg/L for NAA and o.1 mg/L for kinetin. The growth of the Callus seemed to be more simnultaed with the combination of NAA and kinetin than NAA and BA with illumination at all concentration ranges of 1.0 to 4.0 mg/l for NAA and o.1 to 1.0 mg/L for kinetin or BA studied. Amogn 8 different media used, the induction rate of callus on Anderson, Eriksson, and Shenk and Hildebrant at 4 weeks after the innoculation was almost the same as that of MS. However, callus was rarely induced on Heller or White medium. Suspension cultures were easily initiated with 3 g of callus (fresh weight) derived from ginkgo leaves on supplemented MS medium. A typical growth curve of suspension cultured cells could be obtained by measuring the fresh weight of the suspension cultured cells at every 3 days. To improve the growth of suspension cultured cells of ginkgo, effects of concentrations of NAA, sucrose, phosphate ions and molar ratio of $NH_{4}^+\;to\;NO_{3}^-$ ions in the culture medium were studied. The maximum growth of the cells was achieved when the culture medium contained 1.0 mg/L of NAA, 30 g/L sucrose, 1.75 mM phosphate ions and 1:5 molar ratio of $NH_{4}\;to\;NO_{3}^-$ ions.

Several new coumarinoyl and coumarionyl-1, 2, 4-triazole derivatives were synthesised via dipolar cycloaddition reactions with 3-coumainohydraziodoyl halide. Structure were based on elemental analysis and spectral data.

For the evaluation of the role of .alpha., .betha.-unsaturated ketone portion of ar-tumerone for its activity, the structural variation of this structural unit was performed to omit its alkylating propery. Thus compounds 2, 3, and 4 were prepared and their cytotoxicities were determined against three different leukemiz cell lines (HL-60, K-562, and $L_{1210})$ in vitro. The biological inactivity against three different cell lines of these analogues implies that the $\alpha, \beta$-unsaturated ketone of ar-tumerone is the essential pharmacophore for its activity.