The present investigation deals with the synthesis of some new salicylamidoacetyl sulfonamides 3a,b, salicylamido ethylacetate 4, salicylamido acetic acid hydrazide 5, which is considered as the key intermediate for the synthesis of several series of new compounds such as salicylamido pyrazol 6 and pyrazolone 1. N-imido-derivatives 9, 10, 11, thiadiazole 13, oxadiazole 14, 15, Schiffs bases 16a-f. Cyclocondensation of Schiffs bases with thioglycolic acid gave thiazolidinone 18a-c while with acetylchloride afforded azitidinones 19a-c and with acetic anhydride gave 1,4-benzoxazepine-3,5-dione. Some of the compounds were tested for their analgesic and antiinflammatory activities as well as ulcerogenic effects. Some derivatives were more effective than salicylamide and ulcerogenic activity was variably lowered .

A new series of pyridazine, pyrazoles, pyrazolidine-3,5-dione, Semicarbazide, thiosemicarbazides, hydantoin, thiohydantoins, 1,2,4-triazoles, S-triazolo[3,4-b]-1,3,4-thiadiazoles incorporated indirectly into salicylamide moiety at position 2 were synthesized. Also the synthesis of novel series of 3-salicylamido-2-hydroxypropyl-amino derivatives were prepared. Several of these compounds were screened for antiinflammatory, analgesic, antipyretic and ulcerogenic activities.

Various analogues of 5,8-dimethoxy-1,4-naphthoquinone (DMNQ) such as 2- or 6-(1-hydroxyiminoalkyl)-DMNQs were prepared and evaluated for the antitumor action. (1 -Hydroxyiminoalkyl)-DMNQs derivatives expressed greater antitumor action than (1-hydroxyalkyl) - or acyl-DMNQ derivatives. Moreover, 6-(1-hydroxyiminoalkyl)-DMNQ derivatives expressed higher antitumor action than 2-substituted ones, suggestive of a steric effect. Some of 6-(1-propyloxyalkyl)-DMNQ derivatives with an alkyl group of butyl to octyl moiety showed T/C values of >400%

The phytochemical study of the aerial parts of Artemisia japonica ssp. littoricola (Asteraceae) led to the isolation of two acetylenic compounds, (3R)-dehydrofalcarinol (2) and (3R)-dehydrofalcarindiol (6), two sesquiterpenes, $1{\beta}$, $6{\alpha}$-dihydroxy-4(15)-eudesmene (5) and oplodiol (8), and four phenolic compounds, eugenol (1), vanillin (3), 3'-methoxy-4'- hydroxy-trrans-cinnamaldehyde (4) and p-hydroxyacetophenone (7). Their structures were determined by chemical and spectroscopic methods.

Four lignan xylosides and two neolignan glycosides were isolated from the stem and root barks of Ulmus davidiana var. japonica. Their structures were identified as lyoniside, nudiposide, 5'-methoxyisolarciresinol-9'-O-$\beta$- D-xylopyranoside, isolariciresiol-9'-O-$\beta$-D-xylopyranoside, rel-trans-dihydrodehydroconiferyl alcohol 4'-O-$\alpha$-L-rhamnopyranoside and icariside E3 by comparison of their spectral data with those reported in the literatures, respectively.

The effects of various sedative cyclopeptides and peptide alkaloids from the Zizyphus species on calmodulin-dependent $Ca^{2+}$ -ATPase and phosphodiesterase were Investigated. Calmodulin-induced activation of $Ca^{2+}$-ATPase was strongly inhibited by sanjoinine-A dialdehyde (IC_{50}$, 2.3$\mu\textrm{m}$), -Ah1 (IC_{50}$, 4.0$\mu\textrm{m}$), -A (IC, 4.6$\mu\textrm{m}$), and -G2 (IC_{50}$, 7.2$\mu\textrm{m}$), while calmodulin-induced activation of phosphodiesterase was strongly inhibited by both deachuine- S10 (IC_{50}$, 4.9$\mu\textrm{m}$) and sanjoinine-D (IC_{50}$, 9.0$\mu\textrm{m}$). The inhibitory activity of the various cyclopeptides and peptide alkaloids on $Ca^{2+}$-ATPase was found to correlate well with their Sedative activity.

A fully automated high performance liquid chromatography with column-switching was developed for the simultaneous determination of KR60436, a new reversible proton pump inhibitor, and its active metabolite O-Demethyl-KR60436 from rat plasma samples. Plasma sample (50$\mu$l) was directly introduced onto a Capcell Pak MF Ph-1 column ($10{\times}4$ mm I.D.) where primary separation was occurred to remove proteins and concentrate target Substances Using acetonitrile-Potassium Phosphate (PH 7, 0.1 M) (2 : 8, v/v). The drug molecules eluted from MF Ph-1 column were focused in an intermediate column ($10{\times}2$ I.D.) by the valve switching step. The substances enriched in intermediate column were eluted and separated on a Vydac 218MR53 column ($250{\times}3.2$ I.D.) using acetonitrilepotassium phosphate (pH 7, 0.02 M) (47:53, v/v) at a flow rate of 0.5 ml/min when the valve status was switched back to A position. The method showed excellent sensitivity (detection limit of 2 ng/ml) with small volume of samples ($50{\mu}$l), good precision and accuracy, and speed (total analysis time 24 min) without any loss in chromatographic efficiency. The response was linear ($r^2{\geq}0.797$) over the concentration range of 5-500 ng/ml.

A coumestan derivative, psoralidin (1) was found to be a cytotoxic principle of the seeds of Psoralea corylifolia L (Leguminosae) with the IC_{50}$ values of 0.3 and 0.4 ug/ml against the HT-29 (colon) and MCF-7 (breast) human cancer cell lines, respectively. A coumarin, angelicin (2) was also isolated as a marginally cytotoxic agent along with an inactive compound, psoralene (3) from the plant. The isolates 1-3 were not active against the A54l(lung) and HepG2 (liver hepatoma) cancer cell lines.

The mechanisms responsible for the antidiabetic activity of both the white ginseng radix (Ginseng Radix Alba, GRA) and the rootlet (Cinseng Radix Palva, GRP) were investigated. After a four week oral administration, the fasting blood glucose levels in the GRA- and GRP-treated groups were lower when compared to the control group. To elucidate the hypoglycemic mechanism(s) of the ginseng radices, glucose absorption from the small intestine, hepatic hexokinase and glucose-6-phosphatase activities, in addition to PPAR-${\gamma}$ expression in adipose tissue were examined. The results strongly suggest that GRA can improve hyperglycemia in KKAy mice, possibly by blocking intestinal glucose absorption and inhibiting hepatic glucose-6-phosphatase, and GRP through the upregulation of adipocytic PPAR-$\gamma$ protein expression as well as inhibiting intestinal glucose absorption.

Nasal absorption of procyclidine, a synthetic anticholinergic compound, was investigated in Wistar rats and Beagle dogs. The dosing solution was prepared by dissolving$^{14}C$-procyclidme in 50% ethanolic saline. The dosing solution was administered intravenously and intranasally to rats at a dose of 0.6 mg/kg (i.e., $60{\mu}$l/kg in the form of a 1% w/v solution), and intravenously, orally and intranasally to doss at a dose of 0.3 mg/kg(i.e., $6{mu}$l/kg in the form of a 5% w/v solution). Blood samples were taken from an artery of the animals through the catheter for periods of 1200 (for rats) and 1440 min (for dogs), and the radioactivity in the samples was determined by liquid scintillation counting. The nasal bioavailability of Procyclidine in rats and dogs, based on the radioactivity was calculated to be 81.1 and 98.6% respectively. In both rats and dogs, the plasma profiles of procyclidine following nasal administration were very close to those following intravenous administration, leading to nearly superimposable profiles between the two protocols. In dogs, nasal administration resulted in significantly higher plasma concentrations during the first 30 min period compared to oral administration, suggesting the superiority of the nasal route over the oral route in terms of a prompt expression of the pharmacological effect of the drug. The results obtained in this study indicate that procyclidine is rapidly and nearly completely absorbed via the nasal route. In conclusion, nasal administration represents a viable alternative to intravenous administration in the case of procyclidine.

DA-5018, a recently synthesized capsaicin analog, appears to possess potent analgesic activity when administered topically. The objective of this study is to test the feasibility of the topical administration of this compound. Specifically, our goal was to identify vehicle system that permit a reasonable transdermal permeation of the compound in mice. Among the vehicles examined, isopropyl myristate (IPM) showed the largest in vitro permeability across the intact skin (83.6 ${\pm}$ 5.42${\mu}$l/$\textrm{cm}^2$/h ). However, due to the limited solubility of DA-5018 in IPM (0.53 mg/ml), the maximal flux from the IPM medium remained at only 44.3 ${\pm}2.87{\mu}$g/$\textrm{cm}^2$/hr. In order to increase the flux, addition of better solvents for DA-5018 was attempted, under the assumption that flux is the result of both solubility and permeability. Ethoxydiglycol (EG) and oleic acid (OA) were selected as examples of food solvents. The addition of IC or OA to IPM at a 1:1 volume ratio resulted in a comparable increase in the solubility of the compound (i.e., to 61.1 and 50.2 mg/ml for EG and OA, respectively). However, the addition of EG at a 1:1 volume ratio, for example, increased the flux 6.3 fold (i.e., $279{\mu}$g/$\textrm{cm}^2$/hr), while OA, at a 1:1 volume ratio, decreased the flux 5 fold (i.e., $9.26{\mu}$g/$\textrm{cm}^2$//hr). The mechanism of this discrepancy between EG and OA was investigated by measuring the permeabilty of DA-5018 across the stratum corneum-removed skin of the mouse, under the hypothesis that the viable skin layer may serve as a barrier for the permeation of lipophilic substances such as DA 5018. The permeability of DA-5018, from the medium of EG or OA, across the viable skin differed greatly for EG ($0.41{\mu}$l/$\textrm{cm}^2$/hr) and OA ($0.086{\mu}$l/$\textrm{cm}^2$/hr), suggesting that a higher permeability across the viable skin layer is needed for the second solvents. The maximum flux across the intact skin was achieved for DA-5018 when EG was added to IPM at a 1:1 volume ratio. Thus, the use of a binary system appears to be the best approach for realizing the transdermal delivery of DA-5018 at a reasonable rate.

This Paper deals with the development of a technology for making a hydrophilic gel of Polyethylene oxide reception in which radiating ability is employed to cause cross-linking of Polymers in a water solution. The gel of polyethylene oxide was shown to be nontoxic contain 5-50% of polymer and be useful in composite medicinal forms along with biologically active substances including Bac. subtilis proteases. Proteases immobilized in the gel possess high thermal stability and proteolytic activity and are readily applied in medicine. The effect of immobilized proteolytic and glucolytic enzymes of Bac. subtillis (Immozimase) on the warm ischemia-reperfusion (I/R) which can cause hepatic and jejunum injury was also studied. These enzymes were immobilized on water-soluble polymer polyethylene glycol by means of an electron beam. The number of degraanulated mast cells as well as serum ALT after I/R in the group with Immozimase was decreased to almost half as compared with the control group. Pretreatment with Immozimase resulted in significant reduction of hepatic and gut neutrophil accumulation as compared with control animals. It was concluded that Immozimase has a protective effect for hepatic and gut ischemia/reperfusion, and this effect seems to be associated with prevention of leukocyte accumulation .

Three types of learning and memory tests (Morris water maze, active and passive avoidance) were performed in rats following intracerebroventricular infusion of ethylcholine aziridium (AF64A). In Morris water maze, AF64A-treated rats showed the delayed latencies to find the platform iron 6th day after the infusion. In pretrained rats, AF64A caused the significant delay of latency at 7th days but not 8th day. In the active avoidance for the pretrained rats, the escape latency was significantly delayed in AF64A-treatment. The percentages of avoidance in AF64A-treated rats were less increased than those in the control. Especially, the percentage of no response in the AF64A-treated rats was markedly increased in the first half trials. In the passive avoidance, AF64A-treated rats shortened the latency 1.5 h after the electronic shock, but not 24 h. AF64A also caused the pretrained rats to shorten the latency 7th day after the infusion, but not 8th day. These results indicate that AF64A might impair the learning and memory. However, these results indicate that the disturbed memory by AF64A might rapidly recover after the first retrain. Furthermore, these results suggest that AF64A may be a useful agent for the animal model of learning for Spatial cognition .

The present study was attempted to investigate the effect of quinine on secretion of catecholamines (CA) etroked by cholinergic stimulation and membrane depolarization from the isolated perfused rat adrenal gland. The perfusion of quinine (15-150${\mu}$M) into an adrenal vein for 60 min produced dose- and time-dependent inhibition in CA secretion evoked by ACh ($5.32{\times}10^{-3}M$), high $K^{+}5.6{\times}10^{-2}M$, DMPP ($10^{-4}M$ for 2 min), McN-A-343 ($10^{-4}M$ for 2 min), cyclopiazonic acid ($10^{-5}$ for 4 min) and Bay-K-8644 ($10^{-5}$ M for 4 min). Also, under the presence of pinacidil ($10^{-4}$ M), which is also known to be a selective potassium channel activator, CA secretory responses evoked by ACh, high potassium, DMPP McN-A-343, Bay-K-8644 and cyclopiazonic acid were also greatly reduced. When preloaded along with quinine ($5{\times}10^{-5}M$) and glibenclamide ($10^{-6}$ M), a specific blocker of ATP-regulated potassium channels, CA secretory responses evoked by ACh, high potassium, DMPP McN-A-343, Bay-K-8644 and cyclopiazonic acid were recovered as compared to those of quinine-treatment only. taken together, these results demonstrate that quinine inhibits CA secretion evoked by stimulation of cholinergic (both nicotinic and muscarinic) receptors as well as by membrane depolarization through inhibiting influx of extracellular calcium and release in intracellular calcium in the rat adrenmodullary chromaffin cells. These findings suggest that activation of potassium channels may be involved at least in inhibitory action of quinine on CA secretion from the rat adrenal gland.

We studied the effect of aqueous extract of Magnolia officinalis bark (Magnoliaceae) (MOAE) on the immediate hypersensitivity reaction. MOAE (0.01 to 1g/kg) dose-dependently inhibited compound 48/80 induced systemic anaphylaxis in rats. MOAE (0.1 and 1g/kg) also significantly inhibited local immunoglobulin E (lgE)-mediated passive cutaneous anaphylactic reaction. When MOAE was pretreated at concentrations ranging from 0.01 to 1g/kg, the levels of plasma histamine were reduced in a dose-dependent manner. MOAE (0.001 to 1 mg/ml) dose-dependently inhibited the histamine release from rat peritoneal mast cells (RPMC) activated by compound 48/80 or anti-dinitrophenyl (DNP) Igl. The level of cyclic AMP (CAMP) in RPMC, when MOAE was added, significantly increased compared with that of the normal control. Moreover, MOAE (0.01 to 1 mg/ml) had a significant inhibitory effect on anti-DNP Igl-induced tumor necrosis factor-$\alpha$ production from RPMC. These results indicate that MOAE inhibits immediate hypersensitivity reaction in vivo and in vitro.

Allergenicity of genetically-modified (GM) soybean was evaluated in male Sprague Dawley rats. To confirm the GM soybean used in this study, the polymerase chain reaction (PCR) was performed using the chromosomal DNA of soybeans. The PCR result provided the clear discrimination of genetically-modified (GM) soybeans. To evaluate the allergenicity of GM soybean and non-GM control one, the soybean homogenate was sensitized subcutaneously 3 times a week for 3 weeks. The doses of soybean were 0, 2 and 20 mg/kg in the protein basis. A week after the last sensitization, antisera were recovered from individual animals. When the sera were injected intradermally on the clipped back of unsensitized rats with various dilutions, followed by a challenge with 20 mg/kg of soybean homogenate containing 1% Evans blue, no sign of passive cutaneous anaphylaxis reaction was detected. In addition, when the sera were treated in the cultures of peritoneal mast cells, the increase of histamine release by anti-(GM soybean) sera was not observed when compared to that by anti-(non-GM soybean) sera. The present results indicate that the GM soybean might not act as a strong allergen in male Sprague Dawley rats.