Mophological normal of unfertilized oocytes, which was collected 12-14 hours after human Chorionic Gonadotropin(jCG) injection, was not influenced by chronically adiministration of cocaine for 2 weeks in mice. Proportion of normal unfertilized oocytes in non-cocaine treated group (control), `0 mg/kg and 20 mg/kg cocaine treated group based on body weight with subcutaneous(s.c.) daily injection of cocaine for 2 weeks were 92.9%, 85.6% and 90.9%, respectively. There is no significant difference between control and cocaine treated groups. Two to 8 cell stage embryos collected 24-48 hours post hCG in control group were 66.7%, whereas, 10 mg/kg and 20 mg/kg groups treated with cocaine was 12.5% and 27.3% respectively. Although control and treated groups are significantly different (p<0.05) the developmental score of 2 to 8 cell stage embryos collected at 24-48 hours post HCG, there is no difference between 10 mg/kg and 20 mg/kg treated with cocaine groups. These results indicated that the normal embryos of the roups of cocaine administration were significantly amested when compared with that of control group. The proportion of 2 to 8 cell stage embryo reaching the blastocyst stage, which were cultured 48-52 hours with 5% $Co_2$ in air at $37^{\circ}C$, were 93.9% in control group and, 70.4% and 71.9% in each 10 mg/kg and to blastocyst in vitro culture was significantly limited embryos obtained from cocanized mice compared with those of control mice. These results suggest that episode of cocaine intoxication can cause impaiment of early embrygenesis in the mouse.

The effect of ccocaine on reproductive system were studied in male ICR mice. daily injection of cocaine HCL (10, and 40 mg/kg s.c for 15 days) disrupted epididymal sperm levels and testicular morphology. These disruptions were manifested in a decreased number of sperum, an increased number of dead sperm as compared with control vehicle, and wre evidenced by vacuolations, multinucleated giant cell formations and coagulation necrosis in the testicular seminiferous tubules. Responses in the current study were trended in dose dependent pattem. These results suggest that thronic cocaine intoxication can perturb on male reproductive organ functioning.

The natural product, spirostanol glycoside dioscin, was shown to directly inactivate human pleural fluid phospholipase $A_2{\;}(PLA_2)$ Inactivation was dose, and time dependent. The $IC_{50}$ was estimated at 18 .mu.M and virtually complete inactivation of the enzyme occurred at 50 .mu.M. Using Michaelis-Menten kinetics, dioscin inactivated the enzyme by a competitive inhibitory manner, the apparent Ki value was $6.9{\times}10_{-4}$. Reversibility was studied directly by dialysis method, the inhibition was reversible. Additioin of excess $Ca^{2+}$ concentration up to 8 mM did not antagonize the inhibitory activity of dioscin. Inactivation of several kinds of $PLA_2$ by dioscin is due to interaction with the active site of $PLA_2$ and may be a useful adjunt in the theraphy of inflammatory diseases.

The titled compounds have been synthesized by the oxidative cyclization of N-ethyl-N'-aryl-thioureas and screened for their anti-inflammatory and analogesic activities. Some of the compounds exhibit significant activities.

The characteristics of voltage-dependent ^{45}Calcium$ uptake and norepinephrine release as factors controlling neural activities in the hypothalamus which is an important regulatory site for cardiovascular function wre studied. Two groups of animals : male spontaneously hyperterisive rat (SHR) and age-matched nomotensive wistar rat (NW) were used in this study. Animals at 4, 6 and 16 weeks of age were sacrificed by decapitiation and the hypothalamus was dissected out. Voltage-dependent calcium uptake and norepinephrine release were determined from hypothalamic synaptosomes either in low potassium (5 mM) or high potassium (41 mM) stimulatory conditions by using ^{45}Ca$ isotope and HPLC-ECD techniques. Degrees of voltage-dependent ^{45}Calcium$ uptake and norepinephrine release evoked by calcium uptake in the hypothalamus of prehypertensive phase (4 weeks old) of SHR were significantly smaller than those in NW of the same age. However, in the developmental phase (6 weeks old) and the established phase (16 weeks old) of hyperrtension in SHR, degrees of voltage-dependent ^{45}Calcium$ uptake and norepinephrine release were similar to those of age-matched normotensive wistae eats. These data imply that the deficit in hypothalamic norepinephrine release might be an important underlying factor for the development of hypertension in SHR.

Fluorenecarboxaldehyde hydrazone 9FCH)was synthesized as a new fluorescent reagent for the determination of acidity. FCH had no fluorescence in itself, however, it strongly fluoresced under acidic conditions at excitation maximum of 392 nm and emission maximum of 447 nm, respectively. It showed good correlation with pH in the range from pH 0.60 to pH 3.60 in strong acids. As an application, the acidity of gastric juice in rats and humans was determined. In comparision with pH-metry, the acidity measured by the developed method showed generally increased values of about 0.7-1.3 unit and 0.8-1.2 unit in rats and humans, respectively. However, these results had statistically close correlation with those of pH-metry and the correlation coefficients were 0.887 in rats and humans between two methods.

The suppressive activity of isoflavonoids against lymphocyte proliferation in vitro was examined. Isoflabvonoid derivatives tested were isflavones isolated from Pueraia radix and synthesized 7-O-substituted biochanin A derivatives. The certain isoflavones such as biochanin A and 2-carbethoxybiochainin A were found to possess the suppressive activity against concanavaline A (Con A)-induced lymphocyte proliferation from mouse spleen. Against mixed lymphocyte culture reaction, biochanin A, 2-carbethoxybiochainin A, daidzein, formononetin, genistein and 7-O-isopropylbiochaninl A showed the suppressive activity at $10^{-5}$ M. However, all isoflavones tested did not show the suppressive activity against lymphocyte proliferation induced by B-cell mitogen, lipopolysaccharide (LPS). In general, isoflavones were revealed to be less active than flavones/flavonols.

Release rates of flurbiprofen from transdermal gels made of poloxamer 407 were evaluated using a membraneless diffusion cell in order to study the effects of formulation variables on flurbiprofen release such as poloxamer 407 (17.5-25%) drug (0.1-1.0%), ethanol (10-20%), PG or PEF 300 (5-15%) concentrations and gel pH(3-7). Isopropyl myristate was employed as a receptor medium for the drug released from the gel. The diffusion coefficient of flurbiprofen decreased linearly as the amount of poloxamer 407 and the drug in the gel increased. The release rate of flurbiprofen was gel increased. The The addition of more ethanol in the gel increased the drug release, resulting from the increase of the thermodynamic activity of the drug in the aqueous phase of the gel. However, the concentration effects of PG and PEG 300 on the release rate of flurbiprofen were negligible over the concentration range used.

A stereoselective and sensitive high performance liquid chromatography using fluoresecence deterctor was examined for the determination of R(-) and S(+)-salbutamol in human plasma. Solid phase extraction method using silica as sorbent was used to extract salbutamol racemates from the plasma matrices. After fractionation and freeze-drying of the eluates containing salbutamol racemates, they were separated and quantified on a chirla stationary column. The detection limit of each enantiomer was 2 ng/ml in human plasma (S/N=3).

An efficient synthetic method for 11-deoxyanthracycline AB synthons is described. A verstile key intemediate vinyl bromide 3 was prepared from 5- methodxy-1-tetralone in three steps, and then was converted to the allylic alcohols 4 and 8 which, in tum, fumished highly fuctionalized AB synthons 7 and 12, respectively, via sequential epoxidation-reduction-protection processes.

This study was conducted to characterize the in vivo pharmacology of KR-30988, KR-30992 and losartan, new AT antagonists, given as i.v. cumulative doses, in two antimal models of high renin, conscious renal artery-ligated hypertensinve rats (RHRs) and nomotensive rats anesthetized with urethane (90 mg/kg, i.p.) and .alpha.-chloralose (90 mg/kg, i.p.), with a special emphasis on the phamacological characterization of the latter model. In conscious RHRs, KR-30988, KR-30992, losartan and captopril caused a dose-dependent decrease in blood pressure, their relative potencise ($ED_{20}$) being 0.057, 0.028, 0164 and 0.018 mg/kg, i.v., repectively. In anesthetized rats, 2 hours after anesthesia, plasma renin activity was increased from 7.31 tp 34.07 ng/ml/h, the level approximately 1.5 times greater than the highest level in RHRs. In anesthtized rats, the $ED_{20}$s for all four compounds were 0.004 mg/kg i.v., respectively. By comparison, $ED_{20}$sfrom anesthetized rats were 4 to 5 times smaller than those from conscious RHRs, with a good correlation (.gamma. = 0.999) noted between thetized rats to the hypotensive activity of the compounds and the same order of potencies intwo models. These results suggest that, in addition to PHRs, the normotensive rats anesthetized as above can serve as a suitable model for the rapid phamacological evaluation of $AT_1$ receptor antagonists.

The effect of the root of Coptis japonica (COPT), both dichloromethane soluble $(CH_2Cl_2)$ and insoluble $(H_2O)$ fractions, on catecholamine contents and tyrosine hydorxylase (TH) activity in PC12 cells was investigated. $(CH_2Cl_2){\;}and{\;}H_2O$ fractions showed 21 and 53% inhibitions on dopamine content, respectively, at a ocncentraction of 40 .mu.g/ml in medium : the $(H_2O)$ fraction proveided a grateer inhibitory effect. The TH activity was reduced by the treatment of COPT ($(H_2O)$ fraction). These results suggest that COPT has an inhibitory effect on the catecholamine biosynthesis by the reduction of TH activity in PC12 cells.

Six flavonoids were isolated from the aerial parts of Cirsium flavonoids were identified as apigenin, luteolin, $pectolinarigenin-7-O-{\betha}-D-glucopyranoside$, linarin, pectolinarin and $hispidulin-7-O-{\alpha}-L-rhamonopyranosyl-(1{\rightarrow}2)-{\betha}-D-glucopyranoside$ on the basis of chemical and spctral evidence.

1,5-diketones(3) undewent cyclization to 4H-pyrano[3,2-d]pyrazoles (4a-d),4H-piperidino[3, 2-d]pyrazole (5) and pyrazolo[5,4-d]thiopyran (6) upon treatment with P/sub 2/O/sub 5/, CH/sub 3/COONH/sub 4/ and /or P/sub 2/S/sub 5/. Moreover, treatment of (4) with CH/sub 3/COONH/sub 4/ and/or P/sub 2/S/sub 5/ afforded (5) and (6). The structures of the hitherto unknown ring systems have been confirmed by analytical and spectral data.

5-sec-butylthiomethyl-5-alkyl (methyl or phenyl) hydantoins (3-x) were prepared by the reaction of sec-buylthiomethyl alkyl (methyl or phenyl) ketone (1-2), potassium cyanide and ammonium carbonate. 3-(2-Bromoethyl) hydantoins (5-6) were the reaction products of 5-sec-buythiomethyl-5-alkyl (methyl or phenyl) hydantoin and 1, 2-dibromothane in the presence of potassium hydroxide. Alkylation of 5 and 6 with an excess of alkyl (methyl or ethyl iodide in THF with sodium hydride as base gave three 1-alkyl (methyl or ethyl)-3-(2-bromoethyl) hydantoins (7-9). Treatment of the 2-bromothyl group with potassium thioacelate and triethylamine gave three 1-alkyl (methyl or ethyl)-3-92-acetylthioethyl) hydantoins (10-12). Hydrolysis of the 2-acetylthiuoethyl group with sodium hydroxide in methanol afforded the three 1-alkyl (methyl or ethyl)-3-(2-mercaptorthyl) hydantoins.

A guaian type sesquiterpene, torilin, was isolated from the hexane extract of the fruits of Torilis japonica. The $^1H{\;}and{\;}^{13}C-sinals$ of this compound have been fully assigned utilizing $^1H-^1H$ COSY, HMQC, and HMBC experiments.