Effects of water produced by oil segment on aquatic organisms after treatment using advanced oxidative processes.

The water produced (PW) by the petroleum industry is a potential contaminant to aquatic biota, due to its complex mixture that may contain polycyclic aromatic hydrocarbons (PAHs), organic chemical compounds, including benzene, toluene, ethylbenzene and xylene (BTEX), metals and other components that are known to be toxic. The aim of this investigation was to examine the acute toxicity produced by a PW sample in aquatic organisms Vibrio fischeri and Daphnia similis prior to and after 4 treatments using advanced oxidative processes such as photocatalysis, photoelectrocatalysis, ozonation and photoelectrocatalytic ozonation. Data demonstrated that exposure to PW was toxic to both organisms, as evidenced by reduced luminescence in bacterium Vibrio fischeri and induced immobility in Daphnia similis. After treatment of PW with 4 different techniques, the PW remained toxic for both tested organisms. However, photoelectrocatalysis was more efficient in decreasing toxicity attributed to PW sample. Therefore, data demonstrate the importance of treating PW for later disposal in the environment in order to mitigate ecotoxicological impacts. Further photoelectrocatalysis appeared to be a promising tool for treating PW samples prior to disposal and exposure of aquatic ecosystems.

Oral administration of bovine lactoferrin attenuates ultraviolet B-induced skin photodamage in hairless mice.

Lactoferrin (LF) is recognized as a host defensive glycoprotein, especially for newborn infants. The aim of this study was to investigate whether orally administered LF had protective activity against UV-induced skin damage in hairless mice. Transepidermal water loss and skin hydration were evaluated in nonirradiated mice, UVB-irradiated mice, and UVB-irradiated and LF-administered mice. Supplementation with LF (1,600 mg/kg per day) effectively suppressed the increase in transepidermal water loss, reduction in skin hydration, aberrant epidermal hyperplasia, and cell apoptosis induced by UV irradiation. Although no significant changes in superoxide dismutase-like activity or malondialdehyde levels were observed in the skin with both UV irradiation and LF administration, UV-stimulated IL-1ß levels in the skin were significantly suppressed by the administration of LF. Oral supplementation with LF has the potential to reduce IL-1ß levels and prevent UV-induced skin damage. Further studies are needed to elucidate the relationships between the antiinflammatory effects and skin protective function of LF.

Antiproliferative constituents in the plants 7. Leaves of Clerodendron bungei and leaves and bark of C. trichotomum.

The constituents of the leaves of Clerodendron bungei STEUD. (Verbenaceae) and leaves and bark of C. trichotomum THUNB. were investigated guided by the antiproliferative activity against three tumor cell lines (MK-1: human gastric adenocarcinoma, HeLa: human uterus carcinoma, and B16F10: murine melanoma). Two phenylethanoid glycoside caffeic acid esters, acteoside and isoacteoside, were isolated as the constituents which selectively inhibit the growth of B16F10 cells. The antiproliferative activities against B16F10 cells of acteoside (GI50: 8 microM), isoacteoside (8 microM) and their methanolysis products, methyl caffeate (26 microM), 3,4-dihydroxyphenethyl alcohol (8 microM), 3,4-dihydroxyphenethyl glucoside (10 microM), desrhamnosyl acteoside (6 microM), and desrhamnosyl isoacteoside (6 microm) suggested that the 3,4-dihydroxyphenethyl alcohol group might be more responsible for the activities of acteoside and isoacteoside than the caffeoyl group. The activities of chlorogenic acid, 3,4-dihydroxyphenylacetic acid, 3-(3,4-dihydroxyphenyl) alanine, 3,4-dihydroxy-phenethylamine hydrochloride, ferulic acid, sinapic acid, and five dihydroxybenzoic acids were also determined and compared with those of the above compounds.

Conduritol F glucosides and terpenoid glucosides from Cynanchum liukiuense and distribution of conduritol F glucosides in several Asclepiadaceous plants.

Conduritol F 3-0- and 4-O-glucosides were obtained from Cynanchum liukiuense, along with conduritol F which was identified in all Asclepiadaceous plants examined, Tylophora tanakae, Asclepias curassavica and A. fruticosa, as well as in Marsdenia tomentosa. The pattern of the glucosidic linkage to conduritol F differed between individual species, 2-O-glucoside from T tanakae and M. tomentosa, 3-O-glucoside from A. curassavica, but none from A. fruticosa. Along with conduritol F glucosides, an 11-glucosyloxy-megastigmane and a monoterpenoid glucoside were isolated from C. liukiuense.

Marstomentosides O-T polyoxypregnane glycosides from Marsdenia tomentosa.

Thirteen pregnane glycosides were isolated from fresh leaves of Marsdenia tomentosa collected in the Fukuyama district. Of these, six were glycosides previously obtained from the same plant collected in the Fukuoka district and one from another Asclepiadaceous plant. The structures of the six new glycosides were determined by spectrometric method.

Pregnanes and pregnane glycosides from Hoya carnosa.

Eleven pregnanes were isolated from the hydrolysate of the CHCl3 extract fractionated from the caules of Hoya carnosa. Among these, six pregnanes, including 19-acetoxydigipurpurogenin II, were new, and their structures were elucidated. The structures of twenty new pregnane tetraosides and pentaosides, named hoyacarnosides A-T, besides three known ones from the CHCl3 extract, were determined.

[The in vitro combination-effect of toremifene with CAF (cyclophosphamide, adriamycin, 5-fluorouracil) on growth of various human mammary carcinomas].

Toremifene (TOR) is a new antiestrogenic agent, a triphenylethylene derivative that was developed as an alternative to tamoxifene (TAM). TOR has been observed to be more effective than TAM with milder toxicity at high doses. We examined the in vitro combination-effect of TOR with cyclophosphamide, adriamycin, 5-fluorouracil and three drug mixture (CAF) on the growth of various human mammary carcinomas. The combination shows a semi-additive or additive growth inhibitory effect on all estrogen positive cells used here except one cell line. In particular, the additive or synergic combination-effect was observed on TAM resistant cells. Furthermore, TOR exhibits a chemosensitizing activity in ADR-resistant cells by expressing P-glycoprotein coded by MDR-1 (multidrug resistance gene). The chemosensitizing activity is dose-dependent of TOR. As described above, the combination of TOR with CAF shows more than a semi-additive effect in this experiment. In conclusion, the addition of high-dose TOR to CAF therapy might be useful for advanced/recurrent breast cancer.

Minor daphnane-type diterpenoids from Wikstroemia retusa.

In addition to huratoxin, pimelea factor P2, and wikstroelides A-G from the fresh bark, eight daphnane-type diterpenoids, wikstroelides H-O, were isolated from the bark and stem, and their structures established. Cytotoxicity was assayed on some wikstroelides.

Triterpenoid glycosides from bark of Meliosma lanceolata.

From the bark of Meliosma lanceolate, nine triterpenoid glycosides including the 28-O-beta-D-glucopyranosyl ester of bayogenin-3-O-beta-D-glucuronopyranoside, its 4'-O-beta-D-galactopyranoside and 4'-O-alpha-L-arabinopyranoside were isolated and the structures characterized along with that of 28-O-beta-D-glucopyranosyl-bayogenin-3-O-beta-D-4'-anhydro-4', 5'-didehydroglucuronopyranoside. Bisdesmosidic triosides of hederagenin were obtained as minor components.

Liquid chromatography combined with thermospray and continuous-flow fast atom bombardment mass spectrometry of glycosides in crude plant extracts.

In crude plant extracts, constituents of biological or pharmaceutical interest often exist in the form of glycosides. Off-line mass spectral investigations of these metabolites require soft ionisation techniques such as desorption chemical ionisation (DCI) or fast atom bombardment (FAB) if information on molecular mass or sugar sequence is desired. In LC-MS, glycosides can be ionised by using thermospray (TSP), continuous-flow fast atom bombardment (CF-FAB) or other interfaces. These techniques are thus potentially applicable to the on-line analysis of glycosides and can be applied to plant extract analysis. Thermospray (TSP) used with ammonium acetate as buffer provides mass spectra similar to those obtained with DCI-MS using NH3 and is potentially applicable to the on-line analysis of relatively small glycosides bearing no more than three sugar units. CF-FAB provides cleaner MS spectra than static FAB due to the lower concentration of the matrix used and can be applied to more polar compounds such as glycosides with a larger number of sugars. The use of a special setup involving post-column addition of the buffer or the matrix and splitting allows LC-UV, TSP LC-MS and CF-FAB LC-MS to be performed with the same standard HPLC conditions. Different crude plant extracts containing various types of glycosides with one to eight sugar units have been analysed by both TSP and CF-FAB. Cardenolides from Nerium odorum (Apocynaceae) and saponins from Swarzia madagascariensis (Leguminosae), Aster scaber and Aster tataricus (Asteraceae) have been studied by LC-MS. The combination of these two interfaces for the HPLC screening of crude plant extracts is discussed.

Glycosides of 19-formylthevetiogenin and 5 alpha-thevetiogenin from Thevetia neriifolia.

C-nor-D-homo-homologues of cannogenin and uzarigenin glycosides were isolated along with known cardenolide glycosides from the frozen fresh leaves of Thevetia neriifolia. A bisdesmosidic tetraoside of 3 beta,14,21-trihydroxy-5 beta,14 beta-pregnan-20-one was also obtained from the polar fraction and the structure established.

Cardiac glycosides and pregnanes from Adenium obesum (studies on the constituents of Adenium. I).

Cardiac glycosides and pregnanes from the roots and the stems of Adenium obesum Roem. et Schult. were investigated. Among 30 cardiac glycosides including 15 known glycosides and 15 new combinations of the known aglycones and sugars, the structures of 11 glycosides were elucidated. Oleandrigenin beta-gentiobiosyl-beta-D-thevetoside was the main glycoside. Neridienone A and 16,17-dihydroneridienone A, common pregnanes in Apocynaceae, were also isolated.

Cardiac glycosides of Beaumontia brevituba and B. murtonii.

Cardiac glycosides from Beaumontia brevituba and B. murtonii were examined. Gentiobiosyl-beta-D-cymaroside and gentiobiosyl-alpha-L-cymaroside of digitoxigenin were isolated from the seeds, unripe fruits, and leaves of B. brevituba, and the leaves of B. murtonii. Oleandrigenin and/or delta 16-digitoxigenin glycosides having the same sugar moieties were not isolated from the leaves of B. brevituba but from the leaves of B. murtonii as well as the seeds of B. brevituba.

Biological activities of deoxyspergualin in autoimmune disease mice.

An assessment of the prophylactic and ameliorative effects of deoxyspergualin (NKT-01), an immunosuppressive agent, was carried out in male MRL/MpJ-lpr/lpr (MRL/1) mice which spontaneously develop lupus-like lesions. When NKT-01 was administered ip daily from the age of either 8 or 19 weeks, diseases such as massive lymphadenopathy, circulating anti-DNA antibody and lupus nephritis were markedly suppressed. The primary response to lipopolysaccharide was significantly reduced in MRL/1 mice administered NKT-01 but the response to sheep red blood cells was not affected. The ability of spleen cells to release interleukins 2 and 3 with or without mitogen was significantly enhanced in mice receiving NKT-01. These findings demonstrate that NKT-01 has therapeutic activity against the development of spontaneous disease in MRL/1 mice.

[Antitumor effect of bestatin combined with bleomycin against hepatoma AH 66 subcutaneously transplanted in rats].

Biological effect of bestatin in combination with bleomycin against rat ascites hepatoma AH 66 was investigated. The combined use of bestatin and bleomycin both at a dose of 0.5 mg/kg was found to have a strong inhibition of the tumor growth. The combined effect was also confirmed histologically as follows. In combination group, increase of necrobiosis area in the tumor lesion, augmentation of infiltration of lymphocytes and macrophages around the solid tumors, and marked replacement of necrotic area by fibrous granular lesion were stronger and more rapidly than that in the other group.

[Safety evaluation of NK 631. Antigenicity, effect on delated hypersensitivity, irritative effect on eye mucous membrane and mutangenicity of pepleomycin (NK 631) (author's transl)].

1. Whether NK 631 is antigenic to guinea pigs and rabbits was studied by the methods of active and passive anaphylactic shock tests, Schultz-Dale reaction, passive cutaneous anaphylaxis, Ouchterlony, tanned red cell haemagglutination test and test according to the U.S. Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics. However, none of the tests proved NK 631 to be antigenic. 2. The immunosuppressive effect of NK 631 was studied by delayed hypersensitivity to picryl chloride in normal and L-1210 tumor bearing mice. Therapeutic dosis of NK 631 was no immunosuppressed but toxic dosis of NK 631 was slightly decreased in ear thickness of delayed hypersensitivity. 3. The acute irritative effect of NK 631 and of bleomycin was studied by single instillation to the rabbit eye mucous membrane with 0.1 ml of either of 10, 33 and 100 mg/ml solution of the drugs in physiological saline. The irritative effect of NK 631 on the eye mucous membrane at each concentration was slightly severe than that of bleomycin at the same concentration. However, the manifestations were only mild to moderate dilatation of the conjunctival and nictating membrane blood vessels and eye mucous, and recovered or were mitigated 48 hours after the instillation. No severe changes such as corneal opacity, corneal desquamation, swelling and deaquamation of the conjunctival and nictating membrane were observed. The histopathological examination revealed no striking changes. 4. Mutagenicity of NK 631 and of bleomycin on Salmonella typhimurium strain TA 100 and TA 98 was studied. It was definitely shown that neither NK 631 nor bleomycin exerted any mutagenic action on either test strains.

[Studies on antitumor activities and pulmonary toxicity of pepleomycin sulfate (NK631) (author's transl)].

The antimicrobial and antitumor activities, and the pulmonary toxicity of pepleomycin (NK631) were studied in comparison with bleomycin (BLM). NK631 showed a broad antimicrobial spectrum against gram positive and gram negative bacteria equally to BLM, and its activity was about twice higher than BLM. NK631 showed higher activity on cultured HeLa S3 cells and higher antitumor effect on the transplanted tumors of Ehrlich solid carcinoma in mice, AH66 and AH66F ascites hepatoma in rats, and lower antitumor effect on Ehrlich ascites carcinoma in mice than BLM. Similarly to BLM, NK631 did not show satisfactory activity on L1210 leukemia in mice. NK631 showed marked effect on chemically induced squamous cell carcinoma, spontaneous lymph sarcoma of a dog, human and dog gastric cancer heterotransplanted in nude mice equally to BLM. Furthermore NK631 exhibited remarkably higher antitumor activity on lymph node metastasis of AH66 ascites hepatoma of rats and chemically induced gastric carcinoma of rats than BLM. Pulmonary toxicity of NK631 was low as 1/3 in incidence and 1/4 in grade of the BLM in old mice system. This trend was confirmed by chemical analysis of hydroxyproline in lung.

[Studies on organ distribution, absorption and excretion of pepleomycin sulfate (NK631) (author's transl)].

1. Organ distribution of pepleomycin (NK631) in mice and rats was studied. NK631 was found at higher levels than bleomycin (BLM) in skin, lung, stomach, solid tumor, etc. in mice and rats. Furthermore NK631 was detected in the mesenteric and lumbar lymph node, esophagus and prostate in rats and also distributed at about twice as high levels as BLM in the AH109A hepatoma cell-metastasized lymph nodes. 2. For the elucidation of reason on low pulmonary toxicity of NK631 which is in spite of 1.5 times highly distribution in lung compared with BLM, inactivation of various BLMs by high molecular fraction of lung of mice and rats was determined. The order of inactivation rate of various BLMs in lung was as follows: BLM-M5196 greater than NK631 greater than BLM greater than BLM-HPE. There is an encouraging coincidence between index of pulmonary fibrosis in mice and inactivating rate in lung. 3. A comparative study on the serum level and urinary excretion of NK631 and BLM was performed in dogs. The blood level and urinary excretion rate of both drugs were almost similar. 4. The blood levels of NK631 were comparable to those of BLM in cancer patients.