The isolated plasma membrane vesicles have been widely used as an in vitro model system for studying the transcellular transport of nutrients and electrolytes in the renal tubule and intestine, and the findings have generated a great deal of information about the mechanisms of the absorptive and the secretory processes. Active secretion of organic anions and cations in the proximal tubule is viewed as a means of eliminating many exogeneous drugs and their metabolites from the body. The tubular secretion involves transport across contraluminal basolateral membranes, and accumulation in the epithelial cells, followed by efflux from the cells across luminal brush border membranes into the tubular fluid.The transport of p-aminohippurate(PAH), a prototype anion, and tetraethylammonium(TEA), a prototype cation, has been characterized using brush border and basolateral membrane vesicles. Data suggest that PAH is transported by a carriermediated system(anion exchange mechanism)in basolateral membranes and by a channellike system in brush border membranes. In contrast, TEA is transported across basolateral membranes via carrier-mediated system, and this process is stimulated by an insidenegative membrane potential. TEA transport across brush border membranes is driven by an H+ gradient via electroneutral H+/TEA antiport system. Furthermore, it has been demonstrated that aminocephalosporins such as cephradine and cephalexin, possessing an α-amino group and a carboxyl group, can be transported via a common carrier system with dipeptides in the intestinal and renal brush border membranes and that their transport is driven by an inward H+ gradient. Thus, the vesicle studies provide new insights into our understanding of intestinal and renal tubular transport mechanisms of drugs.
Retroviridae is a large family of medium-sized enveloped viruses with a complex structure and remarkable enzyme, reverse transcriptase. Uniquely among viruses, the genome is diploid and consists of an inverted dimer of single strand positive-sense ribonucleic acid (RNA).The deoxyribonucleic acid (DNA) copy of the viral genome transcriptase is integrated into the cellular DNA before multiplication occurs. The retroviridae is subdivided into three subfamilies, only two of which are important in human medicine.The subfamily oncoviridae includes the adult T-cell leukemia virus (HTLV-I) while the virus associated with acquired immune deficiency syndrome (AIDS) is a member of the lentiviridae subfamily. Although AIDS virus (HIV) shares its targets cell tropism and ability to form syncytia in the cells with ATLV/HTLV-I. ATLV is endemic in Japan, Africa and Papua New Guinea.ATLV is a very old virus since its origin is probably the same as that of human population.In contract, HIV is a quite new virus which occurred only recent some ten years but the virus has been spread among people in many areas including north and south America, Australia, Europe and Africa.
New active antifungal agents containing 1, 1-disubstituted ethylenes (No.1-5), 1, 2-disubstituted ethylenes (No.6-9) and substitued 2-propen-1-one derivatives (No.10-68) with azole compounds were prepared and structure-activity relationships were presented.(Z)-1-(4-Chloropheny1)-3-(2, 4-dichloropheny1)-2-(1H-imidazol-1-y1)-2-propen-1-one hydrochloride (No.21), (Z)-1- (5-chloro-2-thieny1)-3-(4-chloropheny1)-2-(1H-imidazol-1-y1)-2-propen-1-one (No.55) and (Z)-1-(5-chloro-2-thienyl)-3-(2, 4-dichlorophenyl)-2-(1H-imidazol-1-yl)-2-propen-1-one (No.56) displayed potent broad-spectrum activity not only against dermatophytes but also against yeast cells (Candida albicans).
In order to measure trace amounts of atropine in plant extracts, the radioimmunoassay technique was established.Immunogenic conjugates of haptens A (4'-carboxymethoxyatropine), B (O-succinylatropine), C (N-(carboxymethyl) noratropine) and D (N-(carboxypropyl) noratropine) with bovine serum albumin were synthesized and antisera against atropine (antisera A-D) were obtained from rabbits immunized with these conjugates.The investigation on these antisera indicated that antiserum A had the highest potency and that antiserum B had the lowest cross-reactivity among them.The assay of the atropine level in plant extracts by using antiserum A showed that this technique is much superior to gas-liquid chromatographic method used sofar.
Hypoglycemic activity of several kinds of Japanese tea was examined and bancha was found to have potential hypoglycemic activity in streptozotocin-induced hyperglycemic and normal rats. One of the active principles was purified by chromatograph on Toyopearl HW-50F and diethylaminoethyl-cellulose and determined to be heteropolysaccharide (T-b) consisting of arabinose, D-ribose and D-glucose (5.1 : 4.7 : 1.7), which gave a molecular weight of approximately 4×104.
Effects of 50% ethanol extracts from 14 crude drugs on hair regrowth in normal and high butter diet-pretreated mice which removed the abdominal hair were investigated.The 50% ethanol extracts of Polygonum multiflorum (I), Drynaria fortunei (II), Panax japonicum (VII) and Swertia japonica (XI) showed the promoting effects on hair regrowth in normal mice.I and VII were effective on hair regrowth in high butter diet-pretreated mice.These results suggested that I and VII promote the hair regrowth and could be used as a hair tonic.
Glyco-3β-hydroxy-5-cholen-24-oic acid-bovine serum albumin (BSA) conjugate was prepared by coupling the hapten with the carrier protein through a 3-hemisuccinyl bridge.The antisera obtained from two rabbits elicited by this new antigen showed satisfactory affinity constants (Ka=1.16×107M-1and 2.28×107M-1) and reasonable specificity to glyco-3β-hydroxy-5-cholen-24-oic acid, exhibiting low cross-reactivities with cholesterol (0.01% and 0.27%) and the major human bile acids.Since the both antisera from two rabbits had somewhat different reactivities, with unsaturated bile acid they were able to be used for the determination.
Aqueous extracts prepared from porcine kidneys (PKE) were found to promote colony formation in agar cultures of mouse bone marrow cells stimulated by colony stimulating factor (CSF) and to exhibit no detectable activity of CSF. The extract (PKE) enhanced colony formation about twice in comparison with control. On the cultures of the marrow cells from 5-FU injected mice with PKE, colony enhancement ratio increased to 3 and 1.5 times in comparison with that of control and that of 5-FU untreated mice, respectively.Futhermore, preincubation of bone marrow cells with PKE for 2 or 3 d caused an increase in the number of colony forming units in culture (CFU-C) by a factor of 1.5 of its initial number, whereas preincubation without PKE caused a considerable decrease of CFU-C number.These results suggest that the colony promoting activity of PKE influenced colony growth by enhancing the target cells of CSF. And there is a possibility that the colony promoting activity of PKE is a physiological factor in maintaining the number of CSF-responsive cells by proliferating and differentiating pre-CFU-C.It is found that there is a similarity between the colony promoting activity of PKE and the other sources in regard to heat sensitivity, trypsin sensitivity and some properties of their target cells.
(±)-2-Dimethylamino-2-phenylbutyl 3, 4, 5-trimethoxybenzoate hydrogen maleate (trimebutine maleate. I) or 14C-labeled I was orally administered to rats and mice, and its metabolites in the urine, bile and plasma were fractionated, characterized and quantified.In both species, I was rapidly metabolized and main urinary metabolites were alcoholand acid-moiety metabolites formed by ester hydrolysis, i.e., 2-dimethylamino-2-phenyl-butanol (II) and its N-mono- and di-demethylated forms (III and IV), 3, 4, 5-trimethoxy-benzoic acid (V) and their conjugates.The proportion of the demethylated metabolites among the urinary metabolites was higher in mice than in rats.In the bile, metabolites considered to be O-and N, O-demethylated metabolites of I and their rearranged products of the latter were detected in a conjugated form beside the above urinary metabolites.The most abundant biliary metabolite was a conjugate of II in rats and that of N, O-di-demethylated I in mice. In the plasma, N-mono- and di-demethylated derivatives (VI, VII) of I were detected.The concentration of V in the plasma was by far the highest, followed by those of the alcohol-moiety metabolites, and the concentrations of I, VI and VII were very low.
The mode of anti-inflammatory action of 2-(8-methyl-l0, 11-dihydro-11-oxodibenz[b, f]-oxepin-2-yl)propionic acid (AD-1590), a new non-steroidal anti-inflammatory drug, was investigated mainly in in vitro models. Inhibitory potency (lC50=0.056μM) of AD-1590 for prostaglandin E2 biosynthesis by rat peritoneal macrophages was about 2.2 times that of indomethacin. AD-1590 showed inhibitory activity against carboxymethyl cellulose-induced leukocyte emigration and protein exudation at a local dose of 1.2 mg/pouch in rats and its maximal activity tended to be superior to that of indomethacin. AD-1590 (100μg/ml) inhibited uptake of 3H-thymidine into rat thymocytes in the presence of phytohemagglutinin-P, but not in the absence of it; indomethacin inhibited both the uptakes. Inhibitory potencies of AD-1590 for hypotonic-hyperthermic lysis of rat erythrocytes (IC50=12.0μM) and heat-denaturation of bovine serum albumin (IC50=25.6μM) were about0.5 times that of indomethacin, and about 2.2 times that of diclofenac sodium, respectively. These findings indicated that AD-1590 has inhibitory activities on prostaglandin biosynthesis, leukocyte emigration, heat-denaturation of albumin and lymphocyte transformation, and membrane stabilizing action, but anti-inflammatory drugs tested affect these responses at different degrees. From these results, it is suggested that AD-1590 shows anti-inflammatory activity through the mechanisms generally similar to indomethacin, while it has more potent inhibitory activity for prostaglandin biosynthesis than indomethacin.
To establish the preparing method of the crude drug, kijitsu, 8 kinds of unripe citrus fruit including Citrus unshiu MARCOVITCH as well as C. aurantium L. subsp.amara ENGLER or C. natsudaidai HAYATA were divided horizontally in two parts and dried under the sun-shine or with hot air below 50°C. Four flavonoids (narirutin, naringin, hesperidin and neohesperidin) were determined by high performance liquid chromatography. Flavonoid content of kijitsu prepared with hot air was about 1.5-times that by solar drying. Most of flavonoid was contained in albedo-free peel. Hot air drying gave fine fragrance and greenish color to kijitsu. Furthermore, it saved labor and time compared with the solar drying method.