Long-term effects of UV light on contractility of rat arteries in vivo

Several studies have shown that UV irradiation may be effective for preventing vascular restenosis or vasopasm. However, the long-term effects of UV light on the physiological properties of vessels such as arterial tension have not been elucidated. We therefore studied the long-term effects of UV using rat carotid arteries treated with UV-B light (wavelength = 313 nm, total energy = 14 mJ/mm2). The animals were sacrificed at 1, 7 and 14 days after UV light exposure, and the carotid arteries were studied by light microscopy and the contractile responses of isolated arterial rings were recorded under isometric tension. UV treatment had induced a substantial loss of smooth muscle cells (SMC) along the entire circumference of the media on days 7 and 14, whereas loss of SMC on day 1 was negligible. Contractile responses of arteries that had been exposed to UV light were significantly reduced on days, 1, 7 and 14. The susceptibility of UV-treated arteries to phenylephrine and prostaglandin F2 alpha was significantly decreased on days 1 and 7, but decreased susceptibility was not seen on day 14. Acetylcholine-induced relaxations were not altered by UV treatment. These results suggest that the long-term effect of UV light is an attenuation of smooth muscle contractility without impairment of endothelial function.     

New mu-opioid receptor agonists with phenoxyacetic acid moiety

New muq-opioid receptor (MOR) agonists containing 4-hydroxypiperidine, piperidine and piperazine moieties were synthesized and evaluated to find a peripheral opioid analgesic. Among the synthesized compounds, 12-[1-[3-(N,N-dimethylcarbamoyl)-3,3-diphenylpropyl]-4-hydroxypiperidin-4-yl]phenoxy]acetic acid (8: SS620) having phenoxyacetic acid and 4-hydroxypiperidine moieties showed the highest agonist potency on the MOR in an isolated guinea-pig ileum preparation, and it also had selectivity to the human MOR expressed in Chinese hamster ovary (CHO)-K1 cells compared with the same types of delta- and kappa-opioid receptors (DOR and KOR). In addition, compound 8 showed a 10 times more potent MOR agonist activity than loperamide. Furthermore, compound 8 showed a peripheral analgesic activity in vivo screening on rat.     

Reaction of C3 and C4 ketoses with alkenals and alkenones in water

Treatment of 1,3-dihydroxyacetone and acrolein with aqueous KOH gave a tetrahydrofuran derivative, 1,4-dihydroxy-3,7-dioxabicyclo[3.3.0]octane, in 80% yield. Similarly, 6-alkyl substituted 1,4-dihydroxy-3,7-dioxabicyclo[3.3.0]octanes were obtained by reaction of 1,3-dihydroxyacetone with various α,β-unsaturated aldehydes. In the cases of long chain alkenals, the reaction was effectively accelerated in the presence of organic co-solvent. On the other hand, the corresponding tricyclic products were synthesized by reaction of 1,3-dihydroxyacetone with cyclic enones, such as 2-cyclopentenone and 2-cyclohexenone. This method was successfully applied to the reaction of a tetrulose in the absence of any protecting groups.     

Cyclization from Higher Excited States of Diarylethenes Having a Substituted Azulene Ring

The cyclization reaction of diarylethenes having an azulene ring occurs only via higher excited states. Novel diarylethenes having an azulene ring with a strong donor or acceptor were synthesized and examined in these reactions. A derivative having an electron-donating 1,3-benzodithiol-2-ylidenemethyl group at the 1-position of the azulene ring showed photochromism, whereas neither a derivative having a π-conjugated electron-donating group at the 3-position of the azulene ring nor derivatives having a π-conjugated electron-withdrawing group at the 1- or 3-position of the azulene ring showed any photochromism. The photoreactivities of these compounds were explained by calculating forces and bond orders on the excited states using density functional theory (DFT) and time-dependent (TD)-DFT.     

Preparation of a specific monoclonal antibody to asiaticoside for the development of an enzyme-linked immunosorbent assay

Asiaticoside (AS), the major active component of Centella asiatica (L.) Urban, is used as a memory enhancer and for wound healing. We have successfully prepared monoclonal antibodies (MAbs) against AS, and developed an enzyme-linked immunosorbent assay (ELISA) system for its determination. AS was conjugated to the carrier protein bovine serum albumin (BSA), which acted as an immunogen. In order to confirm its immunogenicity, the ratio of hapten in the AS-BSA conjugate was determined by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS). After immunization, hybridomas secreting MAbs against AS were produced by fusing splenocytes with the mouse myeloma cell line, SP2/0-Ag14. After the screening, anti-asiaticoside MAb 2B4 was obtained. Weak cross-reactivities occurred with madecassoside (7.08%), but no cross-reactivities were observed with other related triterpenoid glycosides (<0.01%). The assay was suitable for quantitating AS in the range of 0.78 to 50 μg mL(-1). A good correlation of AS concentrations in crude extracts of C. asiatica between ELISA and HPLC methods was obtained (r(2) = 0.999). The contents of AS in various cultivated C. asiatica samples were assayed by the newly established ELISA. The recovery rates of AS in the samples were in the range of 95-103% with coefficients of variation of <10%. The intra- and inter-assay variations were 3.9 and 4.5%, respectively. The ELISA method described should prove useful as an analytical tool for quality control and standardization of medicinal plants and pharmaceutical products containing AS.     

Reversible photocontrol of surface wettability between hydrophilic and superhydrophobic surfaces on an asymmetric diarylethene solid surface

By alternate UV and visible light irradiation, reversible topographical changes were observed on a newly synthesized diarylethene microcrystalline surface between the rough crystalline surface of an open-ring isomer and flat eutectic surfaces. The contact angle changes of a water droplet between 80° and 150° and peak intensities changes of the open-ring isomer in XRD patterns within 2 h of repeating cycle were observed. The results indicated that reversibly photogenerated rod-shaped crystals on the surface were produced based on the lattice of the open-ring isomer crystals in the subphase.     

Improvement of pharmaceutical potential of all-trans retinoic acid with hydroxypropyl-��-cyclodextrin

2-Hydroxypropyl-??-cyclodextrin (HP-??-CyD) includes all-trans retinoic acid (RA), covering the double-bond area of RA with substituted hydroxypropyl groups on CyD ring, as proved by the nuclear Overhauser effect (NOE) between methylene protons on the hydroxypropyl groups and the proton on RA. The formation of an inclusion complex results in hydrophilicity and stability. The effect of RA/HP-??-CyD and that of RA without HP-??-CyD on wrinkle scores and skin elasticity during skin treatment were identical, and the cutaneous stimulus was reduced comparing with RA. The results indicated that the RA/HP-??-CyD complex should help to realize new approaches in skin rejuvenation therapy.     

Palladium-catalyzed denitrogenation reaction of 1,2,3-benzotriazin-4(3H)-ones incorporating isocyanides

1,2,3-Benzotriazin-4(3H)-ones and 1,2,3,4-benzothiatriazine 1,1(2H)-dioxide reacted with isocyanides in the presence of a palladium catalyst to give 3-(imino)isoindolin-1-ones and 3-(imino)thiaisoindoline 1,1-dioxides, respectively, in high yield. An intermediate azapalladacycle was generated through denitrogenation of the triazine moiety, and an isocyanide was incorporated therein.     

The synthetic and biological studies of discorhabdins and related compounds

Various analogues of the marine alkaloids, discorhabdins, have been synthesized. The strategy contains spirocyclization with phenyliodine(III) bis(trifluoroacetate) (PIFA), oxidative fragmentation of the β-amino alcohols with the hypervalent iodine reagent C(6)F(5)I(OCOCF(3))(2), the detosylation and dehydrogenation reaction of the pyrroloiminoquinone unit in the presence of a catalytic amount of NaN(3) and the bridged ether synthesis with HBr-AcOH as the key reactions. All the synthesized compounds were evaluated by in vitro MTT assay for cytotoxic activity against the human colon cancer cell line HCT-116. Furthermore, the discorhabdin A oxa analogues were also evaluated against four kinds of tumor model cells, a human colon cancer cell line (WiDr), a human prostate cancer cell line (DU-145) and murine leukemia cell lines (P388 and L1210). For the identification of the target, discorhabdin A and the discorhabdin A oxa analogue were evaluated by an HCC panel assay. In the test, discorhabdins could have a novel mode of action with the tumor cells.