Sites of Action of Noncompetitive GABA Antagonists in Houseflies and Rats: Three-Dimensional QSAR Analysis

Quantitative structure–activity relationships for insecticidal activity (against houseflies) and competitive activity against a specific [³⁵S]tert-butylbicyclophosphorothionate binding (to rat brain membranes) of some picrotoxinin-type 4-aminobutyric acid antagonists, including γ-BHC, endosulfan, bicyclophosphates, dioxatricyclododecenes and related compounds, were examined three-dimensionally using comparative molecular field analysis (CoMFA). The antagonists were classified into two series according to their molecular shapes: i.e. whether their structure was ‘linearly’ extended beyond the ‘mast-head’ position of the ‘boat-like’ skeletons (series 1) or not (series 2). The CoMFA showed that the slopes in steric and electrostatic fields around the molecule were significant for both series in governing the potency variations in insecticidal and binding activities. Hydrophobicity, a possible factor controlling transport behaviour of compounds, was significant in governing variations in insecticidal activity, but not for the case of the rat membrane binding. Assuming that there is a slight topological difference between series 1 and 2 compounds in terms of the mode of binding with the housefly receptor site, the insecticidal activity was analysable with a single equation for the combined set of compounds, but the rat membrane binding was not. The sterically and electrostatically favourable regions surrounding the molecular series indicated by CoMFA were roughly located at positions so as to interact with the binding subsites on the receptors proposed previously. © of SCI.     

Pre- and postnatal exposure to dieldrin: Persistent stimulatory and behavioral effects

Dieldrin was fed to two generations of albino rats at levels often found in the environment (0.35 μg/kg/day, orally). A two-by-two factorial design was employed to investigate the simultaneous effect of a malnutrition condition consisting of low protein and dieldrin exposure. Second generation animals were tested using comprehensive behavioral criteria (swimming ability, righting reflex, motivational test, and a series of learning tasks) in order to detect any subtle diffeences between groups. Significant differences were seen between all of the test groups in the development of swimming ability. Animals in the 10% protein plus dieldrin (10% + D) were significantly inferior to the 10% protein group. However, rats in the 20% protein plus dieldrin (20% + D) were superior to all of the other groups in overall swimming ability. Both dieldrin groups were significantly superior to their control groups in the retention test (running the animals on the same problem 48 hr later), thus suggesting a stimulatory effect of low-dose dieldrin. No implication is made to suggest that the stimulatory effect is not harmful, since the consequences of such effects have not been determined by long-term studies.     

Identification of metabolites of (-)-epicatechin gallate and their metabolic fate in the rat

After intravenous administration of (-)-epicatechin gallate to Wistar male rats, its biliary metabolites were examined. Deconjugated forms of (-)-epicatechin gallate metabolites were prepared by beta-glucuronidase/sulfatase treatment and purified by HPLC. Five compounds were subjected to FAB-MS and NMR analyses. These metabolites were shown to be (-)-epicatechin gallate, 3'-O-methyl-(-)-epicatechin gallate, 4'-O-methyl-(-)-epicatechin gallate, 4' '-O-methyl-(-)-epicatechin gallate, and 3',4' '-di-O-methyl-(-)-epicatechin gallate. After oral administration, five major metabolites excreted in rat urine were purified in their deconjugated forms and their chemical structures identified. They were degradation products from (-)-epicatechin gallate, pyrogallol, 5-(3,4-dihydroxyphenyl)-gamma-valerolactone, 4-hydroxy-5-(3,4-dihydroxyphenyl)valeric acid, 3-(3-hydroxyphenyl)propionic acid, and m-coumaric acid. Time course analysis of the identified (-)-epicatechin gallate metabolites showed that (-)-epicatechin gallate and its conjugate appeared in the plasma with their highest levels 0.5 h after oral administration; their levels rapidly decreased, and then they disappeared by 6 h. The degradation products, mainly in their conjugated forms, emerged at 6 h, peaked at 24 h, and disappeared by 48 h. In urine samples, (-)-epicatechin gallate and its methylated metabolites were hardly detected and the degradation products began to be excreted in the 6-24 h period, peaked in the 24-48 h period, and then began to disappear. The most abundant metabolite in both the plasma and the urine was found to be the conjugated form of pyrogallol. On the basis of these results, a possible metabolic route of (-)-epicatechin gallate orally administered to the rat is proposed.     

Evaluation of the NO scavenging activity of procyanidin in grape seed by use of the TMA-PTIO/NOC 7 ESR system

The nitrogen monoxide (NO) scavenging activity of grape seed extract (GSE) was studied in the TMA-PTIO/NOC 7 system. The procyanidin-rich (>95%) GSE showed strong NO scavenging activity in the system. The activity was found to depend on the condensation rate of cyanidin when synthetic oligomers were tested. Investigation of the NO scavenging activities of other polyphenols (catechin, epicatechin, epigallocatechin, and epigallocatechin gallate) in the TMA-PTIO/NOC 7 system revealed that gallocatechin, epigallocatechin, and epigallocatechin gallate exhibited strong activities. From the results, it was suggested that the high condensation rate of and the gallate ester moiety in procyanidin in GSE may play an important role in the NO scavenging activity. The mechanism of the NO scavenging activity of phenolic compounds such as GSE is speculated to be as follows: NO reacts with phenolic compounds directly to generate phenoxy radicals.     

Anti-inflammatory potency of oral disulfiram compared with dexamethasone on endotoxin-induced uveitis in rats

To investigate potency of oral disulfiram (DSF) compared with that of dexamethasone (Dexa), on endotoxin-induced uveitis (EIU) in rats. The oral administration with 750 mg/kg DSF suppressed the number of inflammatory cells, protein concentration, and levels of tumor necrosis factor (TNF)-α, Nitric oxide (NO) and prostaglandin (PG) E2 in the aqueous humor and improved the histiologic status of the ocular tissue at 24 hr after lipopolysaccharide (LPS) injection. The anti-inflammatory potency of DSF oral administration was as strong as that observed with 0.5 mg/kg Dexa in the present study. The results suggest that DSF might pave the way for a novel therapeutic agent for the management of uveitis.     

Determination of free phosphoric acid in superphosphate

Water soluble phosphoric acid in ordinary superphosphate and double (or triple) superphosphate consists of mainly monocalcium phosphate, but it also contains one to several per cent free phosphoric acid. Both free acid and water are the essential components in order to know the change in curing or to estimate the reduction of posphoric acid in manufacture of mixed fertilizer.     

Effects of alkali,mild steam,and chitosan treatments on the properties of pineapple,ramie, and sansevieria fiber bundles

This study focused on the effects of treatments of alkali, mild steam, and chitosan on the surface morphology, fiber texture, and tensile properties of pineapple, ramie, and sansevieria fiber bundles. The fibers were treated with NaOH (2%), mild steam (0.1 MPa), and chitosan solutions (4% and 8%). The properties of these treated fibers were characterized and compared with the untreated fibers. Field emission scanning electron microscopy (FE-SEM) was used to observe the surface morphology of those fibers. X-Ray diffraction (XRD) spectroscopy was used to observe the fiber textures. Tensile properties of the treated and untreated fibers were also recorded. SEM micrographs showed that the surfaces of the NaOH-treated fibers were more damaged than those of the steam-treated fibers. The 4% chitosan solution covered the fiber surface more uniformly than the 8% chitosan solution. The steam-treated fibers had higher values of degree of crystallinity, crystallite orientation factor, and crystallite size than the NaOHtreated fibers. Ramie fiber showed greater mechanical properties than the other fibers. The values of tensile strength, Young’s modulus, and toughness of the steamtreated fibers, which were similar to those of the 4% chitosan-coated fibers, were higher than those for the other treatments.     

Pharmacological effects of Ganoderma lucidum collected from ume (Japanese apricot) trees

We performed functional evaluation of the fruiting bodies of Ganoderma lucidum growing on ume trees (Japanese apricot, Prunus mume), and determined the suitability of pruned ume branches as a basic component of culture medium for this mushroom. We observed that all tested functional activities of the fruiting bodies of G. lucidum collected from ume trees were higher than those collected from other broadleaf trees or cultured artificially; the functional tests were angiotensin I-converting enzyme inhibitory activity, a platelet aggregation inhibition test, and an interleukin-8 (IL-8) gene expression inhibition test. When extracts from fruiting bodies of G. lucidum were orally administered to spontaneous hypertensive rats, hypotensive effects were found. Freeze drying was the most suitable procedure for preservation of the extracts, and the activities of 30% ethanol extracts and 30% methanol extracts were higher than those of hot-water extracts. The highest functional activities for extracts from G. lucidum mycelia cultured on sawdust media were for sawdusts based on ume wood. Part of this study was presented at the 56th Annual Meeting of the Japan Wood Research Society, Akita, Japan, August 2006     

Constituents from the roots of <Emphasis Type="Italic">Taxus cuspidata</Emphasis>

The known propelargonidin, afzelechin-(48)-afzelechin (1), the known lignans 7-hydroxynortrachelogenin (2), epinortrachelogenin (3), nortrachelogenin (4), hydroxymatairesinol (5), allohydroxymatairesinol (6), matairesinol (7), oxomatairesinol (8), and isotaxiresinol (9), and the known taxoids taxinine M (10), taxayuntin (11), and 10-deacetyltaxol (12), and 10-deacetylbaccatin III (13) were isolated from the roots of Taxus cuspidata (Japanese yew, Taxaceae). The propelargonidin was isolated from Taxus spp. for the first time, and was detected in the roots, bark, and twigs.