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Sample records for cantharidin

  1. Cantharidin toxicosis in horses.

    Science.gov (United States)

    Schmitz, D G

    1989-01-01

    Cantharidin toxicosis in horses has become an increasing problem in certain regions of the United States. Toxicosis occurs when horses ingest alfalfa hay or products that are contaminated with "blister" beetles. Clinical signs may vary from depression to severe shock and death, depending upon the amount of toxin ingested. The most frequently observed signs include varying degrees of abdominal pain, anorexia, depression, and signs suggestive of oral irritation. Many horses make frequent attempts to void urine. Less commonly observed signs include synchronous diaphragmatic flutter and erosions of the oral mucosal surfaces. Clinical laboratory abnormalities suggestive of cantharidin toxicosis include persistent hypocalcemia and hypomagnesemia, development of hypoproteinemia, microscopic hematuria, and mild azotemia with inappropriate urine specific gravity. Chemical analysis for cantharidin is accomplished by evaluation of urine or stomach contents. Treatment of cantharidin toxicosis is symptomatic, but must include removal of toxin source. Gastrointestinal protectants, laxative, intravenous fluids, analgesics, diuretics, calcium gluconate, and magnesium are all included in the treatment regimen. Early and vigorous therapy is imperative if it is to be successful. In horses that remain alive for several days, persistence of elevated heart and respiratory rates and increasing serum creatine kinase concentration are associated with a deteriorating condition. Prevention is aimed at timely harvesting of alfalfa hay. Hay fields should be inspected for the presence of beetle clusters before harvesting. Involved areas of the field should not be harvested.

  2. Inhibitory Effect of Cantharidin on Proliferation of A549 Cells

    Institute of Scientific and Technical Information of China (English)

    WANG Xiao-hua; YIN Yuan-qin; SUI Cheng-guang; MENG Fan-dong; MA Ping; JIANG You-hong

    2007-01-01

    Objective: To study the inhibition of Cantharidin against the proliferation of human lung cancer A549 cells and its mechanism. Methods: MTT assay was employed to determine the inhibition of Cantharidin against proliferation of A549 cells and flow Cytometry was applied to analyze A549 cell cycle and the effect of Cantharidin on cell cycle. Results: Cantharidin showed inhibition against the proliferation of A549 cells, and the inhibition was mediated by blocking A549 cell cycle at G2/M phase significantly. Conclusion: Cantharidin exhibits inhibition against the proliferation of human lung cancer A549 cells.

  3. A Novel Approach to the Quantitation of Coeluting Cantharidin and Deuterium Labelled Cantharidin in Blister Beetles (Coleop-tera: Meloidae

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    W Boland

    2007-11-01

    Full Text Available Blister beetles (Coleoptera: Meloidae are the main natural source of cantharidin, but the compound titre is depended on several factors including, age, sex and mating status of the insects. In order to eliminate such uncertainty factors in physio¬logical and chemical studies deuterium labelled cantharidin (D2C with no natural abundance is normally introduced into the beetles' body to use it as a model for studying the cantharidin behaviour in vivo. Experiments were achieved on Mylabris quadripunctata (Col.: Meloidae from Southern France and the beetles were exposed to an artificial diet containing a de¬fined amount of D2C. On the other hand, because of the high similarity between the two compounds they cannot be well quantified by gas chromatography. In order to remove the burden, MRM technique was used for the first time which could successfully create well-defined cantharidin and D2C peaks and hence a precise measurement. MRM technique was exam¬ined using a GC-MS Varian Saturn which collected MS/MS data of more than one compound in the same time window of the chromatogram. It is especially useful when coeluting compounds have different parent ions, i.e. m/z 84 for D2C (coelut¬ing isotopically-labelled compound and m/z 82 for cantharidin (beetle-originated compound. Using the routine GC-MS runs, measurement accuracy may be significantly reduced because the D2C peak is covered by the cantharidin huge peak while MRM could reveal the two coincided peaks of cantharidin and D2C. Therefore MRM is hereby introduced as the method of choice to separate cantharidin from D2C with high sensitivity and thus provide a precise base of quantitation.

  4. A Novel Approach to the Quantitation of Coeluting Cantharidin and Deuterium Labelled Cantharidin in Blister Beetles (Coleop-tera: Meloidae

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    MR Nikbakhtzadeh

    2007-12-01

    Full Text Available Blister beetles (Coleoptera: Meloidae are the main natural source of cantharidin, but the compound titre is depended on several factors including, age, sex and mating status of the insects. In order to eliminate such uncertainty factors in physio¬logical and chemical studies deuterium labelled cantharidin (D2C with no natural abundance is normally introduced into the beetles' body to use it as a model for studying the cantharidin behaviour in vivo. Experiments were achieved on Mylabris quadripunctata (Col.: Meloidae from Southern France and the beetles were exposed to an artificial diet containing a de¬fined amount of D2C. On the other hand, because of the high similarity between the two compounds they cannot be well quantified by gas chromatography. In order to remove the burden, MRM technique was used for the first time which could successfully create well-defined cantharidin and D2C peaks and hence a precise measurement. MRM technique was exam¬ined using a GC-MS Varian Saturn which collected MS/MS data of more than one compound in the same time window of the chromatogram. It is especially useful when coeluting compounds have different parent ions, i.e. m/z 84 for D2C (coelut¬ing isotopically-labelled compound and m/z 82 for cantharidin (beetle-originated compound. Using the routine GC-MS runs, measurement accuracy may be significantly reduced because the D2C peak is covered by the cantharidin huge peak while MRM could reveal the two coincided peaks of cantharidin and D2C. Therefore MRM is hereby introduced as the method of choice to separate cantharidin from D2C with high sensitivity and thus provide a precise base of quantitation.

  5. Cantharidin for the Treatment of Molluscum Contagiosum: A Prospective, Double-Blinded, Placebo-Controlled Trial

    Science.gov (United States)

    Dosal, Jacquelyn Coloe; Stewart, Paul W.; Lin, Ja-An; Williams, Christianna S.; Morrell, Dean S

    2012-01-01

    Background/Objective To study the effects and safety of cantharidin in the treatment of molluscum contagiosum. Methods We conducted a prospective, double-blinded, placebo-controlled, randomized clinical trial to evaluate the safety and efficacy of topical cantharidin for treatment of pediatric molluscum contagiosum in an academic ambulatory care center. Twenty-nine children aged 5–10 with the diagnosis of molluscum contagiosum were enrolled to receive treatment with cantharidin or placebo. The main outcome measure was complete clearance of molluscum lesions. Results In contrast to previous retrospective observational studies, the performance of cantharidin treatment over 2 months was not substantially better than the performance of placebo. Limitations The scope of follow-up was limited to 5 visits over 2 months of treatment. In hindsight, we can hypothesize that a longer follow up period may have captured a greater effect of cantharidin. Conclusion We conclude that during a 2 month period, the magnitude of the cantharidin treatment effects in the target population are, at best, not large. This study provided objective unbiased estimates of the magnitude of cantharidin treatment effects and provided important prospective safety data. Our subjects experienced minimal side effects when treated with cantharidin. PMID:22897595

  6. Chronic Sublethal Effects of Cantharidin on the Diamondback Moth Plutella xylostella (Lepidoptera: Plutellidae

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    Zhengyu Huang

    2015-05-01

    Full Text Available The diamondback moth, Plutella xylostella (Linnaeus (Lepidoptera: Plutellidae, is a major pest of cruciferous vegetables worldwide. Cantharidin, a natural toxin isolated from blister beetles, has been reported to be toxic to P. xylostella. However, little is known on the chronic sublethal effects of cantharidin on this species. In this study, we assessed the changes of susceptibility, development, reproduction and other demographic parameters in both the selected P. xylostella strain (Sub, selected by LC25 cantharidin for consecutive 12 generations and the revertant strain (SubR, derived from the Sub strain without being exposed to cantharidin for 12 generations. Results revealed that the two strains maintained a relatively high-level susceptibility to cantharidin. Severe adverse effects on the population dynamics and fitness in Sub strain were observed. In addition, repeated exposure of P. xylostella to sublethal concentration of cantharidin resulted in negative effects on adult performance and deformities in adults. Although morphologically normal for individuals, the SubR strain exhibited a disadvantage in population growth rate. Our results showed that sublethal concentration of cantharidin exhibited severe negative effects on population growth for longtime. These findings would be useful for assessing the potential effects and risk of cantharidin on P. xylostella and for developing effective integrated pest management.

  7. Cantharidin biosynthesis in a blister beetle: inhibition by 6-fluoromevalonate causes chemical disarmament.

    Science.gov (United States)

    Carrel, J E; Doom, J P; McCormick, J P

    1986-07-15

    Biosynthesis of cantharidin in a blister beetle, Lytta polita, is effectively inhibited by 6-fluoromevalonate. Inhibition is attributed specifically to the fluorine substituent. Biochemical inhibition has not been demonstrated previously for an arthropod's defensive substance.

  8. Structural basis of serine/threonine phosphatase inhibition by the archetypal small molecules cantharidin and norcantharidin.

    Science.gov (United States)

    Bertini, I; Calderone, V; Fragai, M; Luchinat, C; Talluri, E

    2009-08-13

    The inhibition of a subgroup of human serine/threonine protein phosphatases is responsible for the cytotoxicity of cantharidin and norcantharidin against tumor cells. It is shown that the anhydride rings of cantharidin and norcantharidin are hydrolyzed when bound to the catalytic domain of the human serine/threonine protein phosphatases 5 (PP5c), and the high-resolution crystal structures of PP5c complexed with the corresponding dicarboxylic acid derivatives of the two molecules are reported. Norcantharidin shows a unique binding conformation with the catalytically active Mn2PP5c, while cantharidin is characterized by a double conformation in its binding mode to the protein. Different binding modes of norcantharidin are observed depending of whether the starting ligand is in the anhydride or in the dicarboxylic acid form. All these structures will provide the basis for the rational design of new cantharidin-based drugs.

  9. Study on effects of cantharidin on cutaneous leishmaniasis, its mechanism and optimization of the therapeutic modes

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    Fatemeh Maleki

    2015-11-01

    Full Text Available Leishmaniasis is one of the major problems in many countries. Leishmania is flagellated protozoa and causative agent of leishmaniasis which is the most important health problem in many countries especially in developing country. Leishmania major causes cutaneous leishmaniasis (CL. CL is endemic in some part of Iran. Pentavalent antimony compounds are main therapy of CL, they have some side effects due to their toxicity, and also relapse is possible. Cantharidin is terpenoid and vesicant compound that can be found in Meloidae and Oedomeridae family beetles. It was used as treatment to cancer and Wart. It is also apoptosis inducer in various cancer cells. In this study, the effect of 0.5, 1, 2, 5, 10, 20 and 50 µg/ml cantharidin on the L. major promastigotes, non-infected macrophages and infected macrophages with parasite amastigotes was studied by (3-(4,5-dimethyl thiazolyl-2-2,5-diphenyle tetrazolium bromide MTT assay and flow cytometer in vitro. The Effect of cantharidin as 0.5, 0.05 and 0.1% ointment surveyed on the Leishmania lesions in BALB/C as well as. Parasite load as determined by Real Time PCR, and IFN-γ and IL-4 was involved by ELISA. Results showed that the highest cytotoxicity (56.14% in promastigotes was in a group that treated with 50 µg/ml cantharidin after 48h. The rate in non-infected macrophages and infected macrophages was 13.05 % and 30.17% respectively. Maximum cytotoxicity rate in promastigotes treated with 50 µg/ml cantharidin after 72 h was determined 66.48%, 48.52% in non- infected macrophages and 62.24% in infected macrophages after 48h by flow cytometry. Group treated with 0.05% cantharidin had lowest rate of ulcer growth. Ulcer size was increased in group treated with 0.5% cantharidin. IFN-γ value in group treated with cantharidin was less than it in untreated (control group, but IL -4 didn’t change. Cantharidin through blister formation induces inflammatory reaction and neutrophils and macrophages infiltration

  10. Sclerotised spines in the female bursa associated with male's spermatophore production in cantharidin-producing false blister beetles.

    Science.gov (United States)

    Hashimoto, Kosei; Sugawara, Hirotaka; Hayashi, Fumio

    Cantharidin is a defence chemical synthesised in only two beetle families Meloidae and Oedemeridae. In Meloidae, cantharidin is used as a defence chemical in eggs. However, in Oedemeridae the function of cantharidin remains unclear. Based on morphological comparison of female internal reproductive organs in 39 species of Oedemeridae, we found that some species have sclerotised spines in the bursa copulatrix (bursal spines), while others have no such spines. Molecular phylogenetic trees inferred from mitochondrial 16S and nuclear 28S rRNA gene sequences suggested multiple evolutionary origins of bursal spines from an ancestor without spines. In the species which lacked spines, males transferred small amounts of ejaculates to females; however, in species with spines, males transferred large spermatophores. Deposited spermatophores gradually disappeared in the bursa, probably owing to absorption. To compare the amounts of cantharidin in eggs laid by species with and without bursal spines, we constructed a new bioassay system using the small beetle Mecynotarsus tenuipes from the family Anthicidae. M. tenuipes individuals were attracted to droplets of cantharidin/acetone solution, and the level of attraction increased with cantharidin concentration. This bioassay demonstrated that the eggs of Nacerdes caudata and N. katoi, both of which species have conspicuous bursal spines, contain more cantharidin than the eggs of N. waterhousei, which lacks spines. In the former species, males transfer large spermatophores to the female, and spermatophores are eventually broken down and digested within the female's spiny bursa. Thus, females with bursal spines may be able to provide more cantharidin to their eggs.

  11. Norcantharidin, Derivative of Cantharidin, for Cancer Stem Cells

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    Chen-Hsi Hsieh

    2013-01-01

    Full Text Available Cancer stem cells (CSCs existing in human cancers have been demonstrated to be a major cause of cancer treatment resistance, invasion, metastasis, and relapse. Self-renewal pathways, Wnt/β-catenin, Sonic hedgehog (Shh, and the Notch signaling pathway play critical roles in developing CSCs and lead to angiogenesis, migration, invasion, and metastasis. Multidrug resistance (MDR is an unfavorable factor causing the failure of treatments against cancer cells. The most important and thoroughly studied mechanism involved in MDR is the active efflux of chemotherapeutic agents through membrane drug transporters. There is growing evidence that Norcantharidin (NCTD, a water-soluble synthetic small molecule derivative of naturally occurring cantharidin from the medicinal insect blister beetle (Mylabris phalerata Pallas, is capable of chemoprevention and tumor inhibition. We summarize investigations into the modulation of self-renewal pathways and MDR in CSCs by NCTD. This review may aid in further investigation of using NCTD to develop more effective strategies for cancer treatment to reduce resistance and recurrence.

  12. Comparison of Cantharidin Toxicity in Breast Cancer Cells to Two Common Chemotherapeutics

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    Katie M. Kern

    2014-01-01

    Full Text Available As part of a larger study synthesizing a more directed form of chemotherapy, we have begun to assess the efficacy of different potential toxins that could be delivered locally rather than systemically. In doing so, we hope to reduce the systemic side effects commonly observed, while maintaining a high level of toxicity and eliminating the need for metabolic alterations. In a search for this more efficient method for killing cancerous cells, we have begun studying cantharidin, a toxin used in traditional Chinese medicine, as a potential chemotherapeutic. Using an MTT cell viability assay, the toxicity of cantharidin was compared to both cyclophosphamide and paclitaxel in three different breast cancer cell lines: MCF-7, MDA-MB-231, and SK-BR-3. Increasing the concentration of chemotherapy drugs did decrease cell viability in all cell lines when cantharidin and cyclophosphamide were applied; however differences for paclitaxel were cell-specific. Additionally, cantharidin exhibited the highest decrease in cell viability regardless of cell type, indicating it may be a much more potent and less specific chemotherapeutic. These results will help us move forward in developing a potentially more potent treatment for breast cancer that might eliminate the need for subtype-specific treatments.

  13. Cantharidin and its anhydride-modified derivatives: relation of structure to insecticidal activity.

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    Sun, Wenbo; Liu, Zhongyi; Zhang, Yalin

    2012-12-20

    Cantharidin is a natural compound of novel structure with ideal insecticidal activity. However, the relationship of structure to insecticidal activity of cantharidin and its derivatives has not been ever clarified. To explore what determines the insecticidal activity structurally of cantharidin-related compounds, two series target compounds 6 and 7 were synthesized by replacing the anhydride ring of norcantharidin with an aromatic amine or fatty amine with different electron density, respectively. The structures of these compounds were characterized by 1H NMR, 13C NMR and HRMS-ESI. A bioassay showed that compounds 6 (a-m) lacked any larvicidal activity against Plutella xylostella; whereas their ring-opened partners 7 (a-m) provided a variety of larvicidal activities against P. xylostella, and compound 7f indicated the highest larvicidal activity with LC(50) value of 0.43 mM. The present work demonstrated that the form of the compound (cyclic or ring-opened) or their ability to hydrolyze facilely was the key to determine whether it exhibits larvicidal activity. Moreover, it revealed that the improvement of insecticidal activity required a reasonable combination of both aliphatic amide and aromatic amide moieties, and the type of substituent Y on the aniline ring was critical.

  14. Cantharidin Impedes Activity of Glutathione S-Transferase in the Midgut of Helicoverpa armigera Hübner

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    Ya Lin Zhang

    2013-03-01

    Full Text Available Previous investigations have implicated glutathione S-transferases (GSTs as one of the major reasons for insecticide resistance. Therefore, effectiveness of new candidate compounds depends on their ability to inhibit GSTs to prevent metabolic detoxification by insects. Cantharidin, a terpenoid compound of insect origin, has been developed as a bio-pesticide in China, and proves highly toxic to a wide range of insects, especially lepidopteran. In the present study, we test cantharidin as a model compound for its toxicity, effects on the mRNA transcription of a model Helicoverpa armigera glutathione S-transferase gene (HaGST and also for its putative inhibitory effect on the catalytic activity of GSTs, both in vivo and in vitro in Helicoverpa armigera, employing molecular and biochemical methods. Bioassay results showed that cantharidin was highly toxic to H. armigera. Real-time qPCR showed down-regulation of the HaGST at the mRNA transcript ranging from 2.5 to 12.5 folds while biochemical assays showed in vivo inhibition of GSTs in midgut and in vitro inhibition of rHaGST. Binding of cantharidin to HaGST was rationalized by homology and molecular docking simulations using a model GST (1PN9 as a template structure. Molecular docking simulations also confirmed accurate docking of the cantharidin molecule to the active site of HaGST impeding its catalytic activity.

  15. Characterization of glutathione S-transferases from Sus scrofa, Cydia pomonella and Triticum aestivum: their responses to cantharidin.

    Science.gov (United States)

    Yang, Xue-Qing; Zhang, Ya-Lin

    2015-02-01

    Glutathione S-transferases (GSTs) play a key role in detoxification of xenobiotics in organisms. However, their other functions, especially response to the natural toxin cantharidin produced by beetles in the Meloidae and Oedemeridae families, are less known. We obtained GST cDNAs from three sources: Cydia pomonella (CpGSTd1), Sus scrofa (SsGSTα1), and Triticum aestivum (TaGSTf3). The predicted molecular mass is 24.19, 25.28 and 24.49 kDa, respectively. These proteins contain typical N-terminal and C-terminal domains. Recombinant GSTs were heterologously expressed in Escherichia coli as soluble fusion proteins. Their optimal activities are exhibited at pH 7.0-7.5 at 30 °C. Activity of CpGSTd1 is strongly inhibited by cantharidin and cantharidic acid, but is only slightly suppressed by the demethylated analog of cantharidin and cantharidic acid. Enzymatic assays revealed that cantharidin has no effect on SsGSTα1 activity, while it significantly stimulates TaGSTf3 activity, with an EC50 value of 0.3852 mM. Activities of these proteins are potently inhibited by the known GST competitive inhibitor: S-hexylglutathione (GTX). Our results suggest that these GSTs from different sources share similar structural and biochemical characteristics. Our results also suggest that CpGSTd1 might act as a binding protein with cantharidin and its analogs.

  16. Physicochemical Properties and Gastric Mucosa Irritation of Cantharidin-hydroxypropyl-β-cyclodextrin Inclusion Complex

    Institute of Scientific and Technical Information of China (English)

    AN Lin-na; DANG Yun-jie; HU Chun-hui; ZHU Chun-yan

    2012-01-01

    Objective To increase the solubility and relieve the mucous irritation of cantharidin (CA) by preparing cantharidin-hydroxypropyl-β-cyclodextrin (CA/HP-β-CD) inclusion complex.Methods The inclusion complex was prepared by co-evaporation method and characterized by differential scanning calorimetry (DSC),X-ray diffractometry (XRD),and nuclear magnetic resonance (NMR).Results The disappearance of CA as well as the shift of exothermic peaks shown in DSC results indicated the complexation phenomenon.XRD results showed that the crystalline CA pattern had disappeared,and in NMR results,H-5 shifted from δ 3.731to 3.695 after complexation and H-2 shifted from δ 3.626 to 3.598,which suggested that part of the drug had entered the HP-β-CD cavity to form an inclusion complex.The solubility increased 10.3 times after complexation and the mucous irritation of CA was relieved remarkably.Conclusion Through complexation with HP-β-CD,the solubility and dissolution rate of CA are improved significantly,and the irritation of musous is relieved.

  17. Crystal structures and mutagenesis of PPP-family ser/thr protein phosphatases elucidate the selectivity of cantharidin and novel norcantharidin-based inhibitors of PP5C.

    Science.gov (United States)

    Chattopadhyay, Debasish; Swingle, Mark R; Salter, Edward A; Wood, Eric; D'Arcy, Brandon; Zivanov, Catherine; Abney, Kevin; Musiyenko, Alla; Rusin, Scott F; Kettenbach, Arminja; Yet, Larry; Schroeder, Chad E; Golden, Jennifer E; Dunham, Wade H; Gingras, Anne-Claude; Banerjee, Surajit; Forbes, David; Wierzbicki, Andrzej; Honkanen, Richard E

    2016-06-01

    Cantharidin is a natural toxin and an active constituent in a traditional Chinese medicine used to treat tumors. Cantharidin acts as a semi-selective inhibitor of PPP-family ser/thr protein phosphatases. Despite sharing a common catalytic mechanism and marked structural similarity with PP1C, PP2AC and PP5C, human PP4C was found to be insensitive to the inhibitory activity of cantharidin. To explore the molecular basis for this selectivity, we synthesized and tested novel C5/C6-derivatives designed from quantum-based modeling of the interactions revealed in the co-crystal structures of PP5C in complex with cantharidin. Structure-activity relationship studies and analysis of high-resolution (1.25Å) PP5C-inhibitor co-crystal structures reveal close contacts between the inhibitor bridgehead oxygen and both a catalytic metal ion and a non-catalytic phenylalanine residue, the latter of which is substituted by tryptophan in PP4C. Quantum chemistry calculations predicted that steric clashes with the bulkier tryptophan side chain in PP4C would force all cantharidin-based inhibitors into an unfavorable binding mode, disrupting the strong coordination of active site metal ions observed in the PP5C co-crystal structures, thereby rendering PP4C insensitive to the inhibitors. This prediction was confirmed by inhibition studies employing native human PP4C. Mutation of PP5C (F446W) and PP1C (F257W), to mimic the PP4C active site, resulted in markedly suppressed sensitivity to cantharidin. These observations provide insight into the structural basis for the natural selectivity of cantharidin and provide an avenue for PP4C deselection. The novel crystal structures also provide insight into interactions that provide increased selectivity of the C5/C6 modifications for PP5C versus other PPP-family phosphatases.

  18. Pharmacokinetic profile of meropenem, administered at 500 milligrams every 8 hours, in plasma and cantharidin-induced skin blister fluid.

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    Maglio, Dana; Teng, Renli; Thyrum, Per T; Nightingale, Charles H; Nicolau, David P

    2003-05-01

    The pharmacokinetic disposition of meropenem, administered at 500 mg every 8 h, in plasma and cantharidin-induced blister fluid is described. Peak meropenem concentrations in blister fluid lagged behind peak meropenem concentrations in plasma, while a lower elimination rate from blister fluid was also noted. The mean penetration of meropenem into blister fluid was 67%. The pharmacokinetic profile of meropenem in blister fluid supports the utility of this dose in the management of skin and soft tissue infections.

  19. Identification and Biochemical Characterization of Protein Phosphatase 5 from the Cantharidin-Producing Blister Beetle, Epicauta chinensis

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    Xi'en Chen

    2013-12-01

    Full Text Available Protein phosphatase 5 (PP5 is a unique member of serine/threonine phosphatases which has been recognized in regulation of diverse cellular processes. A cDNA fragment encoding PP5 (EcPP5 was cloned and characterized from the cantharidin-producing blister beetle, E. chinensis. EcPP5 contains an open reading frame of 1500 bp that encodes a protein of 56.89 kDa. The deduced amino acid sequence shares 88% and 68% identities to the PP5 of Tribolium castaneum and humans, respectively. Analysis of the primary sequence shows that EcPP5 has three TPR (tetratricopeptide repeat motifs at its N-terminal region and contains a highly conserved C-terminal catalytic domain. RT-PCR reveals that EcPP5 is expressed in all developmental stages and in different tissues. The recombinant EcPP5 (rEcPP5 was produced in Escherichia coli and purified to homogeneity. The purified protein exhibited phosphatase activity towards pNPP (p-nitrophenyl phosphate and phosphopeptides, and its activity can be enhanced by arachidonic acid. In vitro inhibition study revealed that protein phosphatase inhibitors, okadaic acid, cantharidin, norcantharidin and endothall, inhibited its activity. Further, protein phosphatase activity of total soluble protein extract from E. chinensis adults could be impeded by these inhibitors suggesting there might be some mechanism to protect this beetle from being damaged by its self-produced cantharidin.

  20. Suppressions of Migration and Invasion by Cantharidin in TSGH-8301 Human Bladder Carcinoma Cells through the Inhibitions of Matrix Metalloproteinase-2/-9 Signaling

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    Yi-Ping Huang

    2013-01-01

    Full Text Available Cancer metastasis becomes an initial cause of cancer death in human population. In many cancers, it has been shown that the high levels of matrix metalloproteinase (MMP-2 and/or MMP-9 are associated with the invasive phenotypes of cancer cells. In this study, we investigated the effects of cantharidin, a derivative of blister beetles which is one of the traditional Chinese medicines, on the adhesion, migration, and invasion of human bladder cancer TSGH-8301 cells. Cantharidin effectively suppressed TSGH-8301 cell adhesion, migration, and invasion in a concentration-dependent manner. Results from Western blotting, RT-PCR, and gelatin zymography assays indicated that cantharidin blocked the protein levels, gene expression (mRNA, and activities of MMP-2 and -9 in TSGH-8301 cells. Cantharidin also significantly suppressed the protein expressions of p-p38 and p-JNK1/2 in TSGH-8301 cells. Taken together, cantharidin was suggested to present antimetastatic potential via suppressing the levels of MMP-2 and MMP-9 expression that might be mediated by targeting the p38 and JNK1/2 MAPKs pathway in TSGH-8301 human bladder cancer cells.

  1. Investigation of two blood proteins binding to Cantharidin and Norcantharidin by multispectroscopic and chemometrics methods

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    Liu, Rong; Cheng, Zhengjun, E-mail: ncczj1112@126.com; Li, Tian; Jiang, Xiaohui

    2015-01-15

    The interactions of Cantharidin/Norcantharidin (CTD/NCTD) with two blood proteins, i.e., bovine serum albumin (BSA) and bovine hemoglobin (BHb), have been investigated by the fluorescence, UV–vis absorption, and FT-IR spectra under imitated physiological condition. The binding characteristics between CTD/NCTD and BSA/BHb were determined by fluorescence emission and resonance light scattering (RLS) spectra. The quenching mechanism of two blood proteins with CTD/NCTD is a static quenching. Moreover, the experimental data were further analyzed based on multivariate curve resolution-alternating least squares (MCR-ALS) technique to obtain the concentration profiles and pure spectra for three species (BSA/BHb, CTD/NCTD and CTD/NCTD–BSA/BHb complexes) which existed in the interaction procedure. The number of binding sites n and binding constants K{sub b} were calculated at various temperatures. The thermodynamic parameters (such as, ΔG, ΔH, and ΔS) for BSA–CTD/NCTD and BHb–CTD/NCTD systems were calculated by the Van’t Hoff equation and also discussed. The distance r between CTD/NCTD and BSA/BHb were evaluated according to Förster no-radiation energy transfer theory. The results of Fourier transform infrared (FT-IR), synchronous fluorescence and three-dimensional fluorescence spectra showed that the conformations of BSA/BHb altered with the addition of CTD/NCTD. In addition, the effects of common ions on the binding constants of BSA–CTD/NCTD and BHb–CTD/NCTD systems were also discussed.

  2. Laryngeal edema induced by disodium cantharidinate injection%斑蝥酸钠注射液致喉头水肿

    Institute of Scientific and Technical Information of China (English)

    陈小蕾; 吴立强; 赵青

    2013-01-01

      1例72岁男性患者,确诊为左肺腺癌7个月,既往有小牛血清去蛋白过敏史。治疗期间输入斑蝥酸钠注射液约30 min,患者突然烦躁,急发憋闷、喉痒、发声嘶哑、吸气性呼吸困难,口唇明显发绀,三凹征阳性等。立即停止输入,给予氧气吸入,甲强龙、异丙嗪、葡萄糖酸钙抗过敏以及其他对症治疗,约20 min后,患者症状明显改善,口唇发绀及三凹征消失。%  One 72-year-old male patient was diagnosed with left lung adenocarcinoma 7 months ago. He had a history of deproteinised calf blood serum injection allergy. About 30 minutes after the disodium cantharidinate injection was used, the patient suddenly developed dysphoria, oppressed, throat itching, voice hoarse, inspiratory dyspnea, obvious lips hematocyanosis, three depression sign positive and so on. This medicine was immediately stopped. The patient received oxygen inhalation and the therapy of antianaphylaxis by methylprednisolone, promethazine hydrochloride injection, calcium gluconate and other treatments. After about 20 minutes, the symptoms improved obviously, lips hematocyanosis and three depression sign disappeared.

  3. Effect of cantharidin, cephalotaxine and homoharringtonine on "in vitro" models of hepatitis B virus (HBV) and bovine viral diarrhoea virus (BVDV) replication.

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    Romero, Marta R; Serrano, Maria A; Efferth, Thomas; Alvarez, Marcelino; Marin, Jose J

    2007-06-01

    The effect as antiviral agents versus viral hepatitis B and C of three compounds purified from natural products commonly used as remedies in traditional Chinese medicine, cantharidin, cephalotaxine and homoharingtonine, was investigated. To assess the activity of these compounds against flavivirus, we used bovine viral diarrhoea virus (BVDV) as a surrogate for hepatitis C virus (HCV). Anti-BVDV activity was determined by reduction in BVDV-RNA production and protection of infected embryonic bovine trachea (EBTr) cells against the cytopathic effect of BVDV. The effect versus hepatitis B virus (HBV) was investigated by measuring HBsAg and HBV-DNA release from hepatoblastoma HepG2 2.2.15 cells infected with HBV. As positive control we used the standard anti-HBV and anti-HCV drugs, lamivudine and ribavirin, respectively. Up to 100 microM lamivudine and ribavirin did not induce cell toxicity, whereas they induced dose-dependent anti-HBV and anti-BVDV effects, respectively. In the same range, cantharidin, cephalotaxine and homoharringtonine induced toxicity in EBTr cells and had no protective effect against BVDV. In contrast, they were able to inhibit HBV production at concentrations 10- to 100-fold lower than those inducing cell toxicity, which suggests that they are useless for the treatment of infection by flaviviruses, but potentially useful in combined therapy against hepatitis B.

  4. Effects of the Bax channel on cantharidin induced apoptosis of Spodoptera frugiperda Sf9 cells%Bax通道在斑蝥素诱导草地贪夜蛾Sf9细胞凋亡中的作用

    Institute of Scientific and Technical Information of China (English)

    崔高峰; 张鹏飞; 郝少东; 丁凯; 王进忠; 张志勇

    2015-01-01

    Objectives] To investigate the role of the Bax channel on cantharidin-induced cell apoptosis in lepidopteran insects [Methods] Bax channel blocker was used to determine the roles of mitochondrial membrane potential, succinate dehydrogenase activity in mitochondria, and cell morphology, on apoptosis of Sf9 cells derived from fall the armyworm, Spodoptera frugiperda (J.E. Smith) exposed to cantharidin stress. [Results] The results show that Bax channel blocker can delay the decrease of mitochondrial membrane potential and reduce changes in cell morphology, but fail to stop the decline of succinate dehydrogenase activity, in Sf9 cells after treatment with cantharidin. [Conclusion] Bax related channels play a role in cantharidin-induced changes in mitochondrial membrane potential and destruction of cell morphology. However, the Bax channel does not appear to play a role in the suppression of enzyme activity in mitochondria after cantharidin treatment.%【目的】为明确Bax通道在斑蝥素诱导鳞翅目昆虫细胞凋亡过程中的作用。【方法】本文利用Bax通道抑制法测定了斑蝥素诱导鳞翅目昆虫草地贪夜蛾Spodoptera frugiperda(J. E. Smith)细胞系Sf9细胞凋亡过程中线粒体膜电位、线粒体琥珀酸脱氢酶活性及细胞形态等方面的影响。【结果】 Bax 通道被抑制后,斑蝥素诱导造成的Sf9细胞线粒体膜电位的降低时间延迟,细胞形变率下降,但琥珀酸脱氢酶活性的下降未受影响。【结论】 Bax通道参与了斑蝥素引起的Sf9细胞线粒体膜电位改变和细胞形态变化,而与抑制线粒体有关能量代谢的酶无直接关系。

  5. Complex regulation of Arabidopsis AGR1/PIN2-mediated root gravitropic response and basipetal auxin transport by cantharidin-sensitive protein phosphatases

    Science.gov (United States)

    Shin, Heungsop; Shin, Hwa-Soo; Guo, Zibiao; Blancaflor, Elison B.; Masson, Patrick H.; Chen, Rujin

    2005-01-01

    Polar auxin transport, mediated by two distinct plasma membrane-localized auxin influx and efflux carrier proteins/complexes, plays an important role in many plant growth and developmental processes including tropic responses to gravity and light, development of lateral roots and patterning in embryogenesis. We have previously shown that the Arabidopsis AGRAVITROPIC 1/PIN2 gene encodes an auxin efflux component regulating root gravitropism and basipetal auxin transport. However, the regulatory mechanism underlying the function of AGR1/PIN2 is largely unknown. Recently, protein phosphorylation and dephosphorylation mediated by protein kinases and phosphatases, respectively, have been implicated in regulating polar auxin transport and root gravitropism. Here, we examined the effects of chemical inhibitors of protein phosphatases on root gravitropism and basipetal auxin transport, as well as the expression pattern of AGR1/PIN2 gene and the localization of AGR1/PIN2 protein. We also examined the effects of inhibitors of vesicle trafficking and protein kinases. Our data suggest that protein phosphatases, sensitive to cantharidin and okadaic acid, are likely involved in regulating AGR1/PIN2-mediated root basipetal auxin transport and gravitropism, as well as auxin response in the root central elongation zone (CEZ). BFA-sensitive vesicle trafficking may be required for the cycling of AGR1/PIN2 between plasma membrane and the BFA compartment, but not for the AGR1/PIN2-mediated root basipetal auxin transport and auxin response in CEZ cells.

  6. Study on bacterial endotoxins test of disodium cantharidinate and vitamin B_6 injection%斑蝥酸钠维生素B_6注射液细菌内毒素检查法研究

    Institute of Scientific and Technical Information of China (English)

    王贵英; 唐继坤; 潘正兴

    2009-01-01

    Objective:To establish a method for determination of the bacterial endotoxin test in disodium cantharidinate and vitamin B_6 injection.Method:Inhibition and bacterial endotoxin test was performed with amebcyte lysate manufactured by different companies with different specifications according to the method of bacterial endotoxin test approved by Chinese Pharmacopoeia 2005 edition.Results:The original solution had non-interference with the bacterial endotoxin test.The results of bacteria endotoxin test in six batchs all accorded with the standard of the quality control.Conclusion:The results suggested that bacteria endotoxin test can be used as an alternative method for the rabbit pyrogen test for disodium cantharidinate and vitamin B_6 injection.The limits of bacterial endotoxin was 6 EU·mg~(-1).%目的:建立斑蝥酸钠维生素B6注射液的细菌内毒素检查方法.方法:按中国药典2005年版二部附录XIE细菌内毒素检查法进行,用小同厂家不同规格的鲎试剂对小同批号的斑蝥酸钠维牛素B_6注射液进行了干扰试验和细菌内毒素检查.结果:本品原液对细菌内毒素检查无干扰作用.按拟定标准检验,该品种6批样品细菌内毒素检查结果均符合规定.结论:本品可用细菌内毒素检查法代替家兔热原检查法,其细菌内毒素的限值(L)为6 EU·mL~(-1).

  7. 斑蝥素诱导草地贪夜蛾(Spodoptera frugiperda)卵巢细胞系Sf9凋亡的临界条件%Critical Condition of Apoptosis of Spodoptera frugiperda Sf9 Cells Lead by Cantharidin

    Institute of Scientific and Technical Information of China (English)

    张来喜; 杨宝东; 张民照; 王进忠; 张爱环; 张志勇

    2011-01-01

    为进一步利用昆虫细胞研究斑蝥素对鳞翅目昆虫的毒杀机理,采用细胞形态学观察法和DNA凝胶电泳法研究斑蝥素诱导草地贪夜蛾(Spodoptera frugiperda)卵巢细胞系Sf9细胞凋亡的临界条件.结果表明:供试细胞凋亡率与斑蝥素处理剂量、时间呈现密切相关性;在较低剂量处理下,可观察到细胞凋亡.当斑蝥素质量浓度达到6.25 μg/mL,处理细胞3h或3.125 μg/mL处理细胞12h时,斑蝥素处理Sf9导致细胞出现明显畸形、形成凋亡小体等凋亡症状.DNA Ladder条件要求严格,在冰浴条件下,当斑蝥素处理质量浓度达到6.25 μg/mL处理细胞24 h时,或者12.5 μg/mL处理细胞12h时,可观察到明显的DNA梯度条带.%To understand the cantharidin toxicity to lepidopterans, the critical conditions of apoptosis of the Spodoptera frugi-perda Sf9 cells led by the nature chemicals were studied by means of cell morphological observation and DNA Ladder. Results showed that Sf9 morphology was changed and presented apoptosis features with deformity and apoptotic body formation at the condition of cantharidin 6. 25 g/mL for 3 hours or cantharidin 3. 125 g/mL for 12 hours. Ice bath was a necessary condition for DNA Ladder. At the condition of cantharidin 12. 5 g/mL for 12 hours or cantharidin 6. 25 g/mL for 24 hours the DNA Ladders were observed.

  8. Clinical observation of combination of disodium cantharidinate and vitamin B6 injection adjuvant chemotherapy on patients with lung cancer postoperation%斑蝥酸钠维生素B6注射液辅助肺癌术后化疗的临床观察

    Institute of Scientific and Technical Information of China (English)

    刘素艳; 卢军利

    2011-01-01

    目的 观察斑蝥酸钠维生素B6注射液辅助肺癌术后化疗的临床疗效及对化疗毒副反应的影响.方法 将64例肺癌术后患者随机分为2组,治疗组32例在常规化疗及对症处理基础上应用斑蝥酸钠维生素B6注射液;对照组32例予常规化疗及对症处理.2组均治疗2周后观察疗效和化疗毒副反应的发生情况.结果 治疗组有效率59.4%,对照组34.4%,2组有效率比较差异有统计学意义(P<0.05),治疗组疗效优于对照组.2组化疗毒副反应发生率比较差异有统计学意义(P<0.05),治疗组低于对照组.结论 斑蝥酸钠维生素B6注射液具有增强化疗疗效、改善患者症状、减少化疗毒副反应的作用.%Objective To investigate the effect of combination of disodium cantharidinate and vitamin B6 injection adjuvant chemotherapy on patients with lung cancer postoperation. Methods 64 patients with lung cancer postoperation were randomly divided into two groups. Patients in control group ( n = 32) received routine chemotherapy. 32 cases in treatment group received combination of disodium cantharidinate and vitamin B6 injection adjuvant chemotherapy. The therapeutic effect and toxic and side effect were observed after treatment of two weeks. Results The effective rate in treatment group was superior to that in control group ( P < 0. 05 ). Toxic and side effect in treatment group was less than that in control group ( P < 0.05). Conclusion Combination of disodium cantharidinate and vitamin B6 injection can reinforce effect of chemotherapy, improve symptoms of patients, and decrease toxic and side effect of chemotherapy.

  9. Study on the HPLC Fingerprints of Spanish fly Ultra-fine Powder from Different Producing Areas and Content Determination of Cantharidin%不同产地斑蝥超微粉体的HPLC指纹图谱及斑蝥素的含量测定

    Institute of Scientific and Technical Information of China (English)

    何杰; 张水寒; 李跃辉; 万丹; 黄江波

    2014-01-01

    目的:结合斑蝥主要成分斑蝥素的含量测定与指纹图谱,比较不同产地药材化学成分的差异性,为科学评价不同产地斑蝥药材及其超微粉体的质量提供依据.方法:建立斑蝥超微粉体指纹图谱检测方法.采用高效液相色谱(HPLC)法对各产地斑蝥超微粉体进行分析,采用中药色谱指纹图谱相似度评价系统软件比较指纹图谱的相似度,采用SPSS 13.0统计软件对10批样品进行聚类分析,并测定斑蝥素含量.结果:不同产地斑蝥超微粉体指纹图谱有较大相似性,但斑蝥素的含量有一定的差异.聚类分析结果表明,不同产地斑蝥药材存在一定差异,但差别不大.结论:所建立的HPLC指纹图谱具有较好的精密度、重复性和稳定性,结合斑蝥素的含量,可为斑蝥药材及其超微粉体质量评价提供依据.%OBJECTIVE:To compare the difference of chemical components in Spanish fly from different producing areas on the basis of content determination and fingerprints of cantharidin,and to provide reference for quality control of S.fly from different producing areas and its ultra-fine powder.METHODS:Established the fingerprint method of S.fly ultra-fine powder.S.fly ultra-fine powder were determined by HPLC.Chromatographic Fingerprint Similarity Evaluation software was used to analyze the similarity of HPLC fingerprint.Cluster analysis was conducted in 10 batches of sample by using SPSS 13.0 software,and the content of cantharidin was determined.RESULTS:The fingerprints of S.fly ultra-fine powder from different producing areas were similar to each other.The content of cantharidin had little difference.Cluster analysis showed that there was little difference in S.fly from different producing areas.CONCLUSIONS:Established HPLC fingerprint is precise,reproducible and stable,and combined with content determination of cantharidin to provide reference for quality evaluation of S.fly and its ultra-fine powder.

  10. Treatment of Advanced Lung Cancer with Sodium Cantharidinate and Vitamin B6 Injection in Combination with Chemotherapy%斑蝥酸钠维生素B6注射液联合化疗治疗晚期肺癌

    Institute of Scientific and Technical Information of China (English)

    林矫; 骆小敏; 董粉英; 王忠

    2011-01-01

    Objective:To observe the clinical therapeutic effect and toxic reaction of sodium cantharidinate and vitamin B6 injection on the treatment of advanced lung cancer. Method;68 advanced non-small cell lung cancer patients were randomly divided into a treatment group (35 cases) and a controlled group (33 cases). The treatment group accepted chemotherapy in combination with sodium cantharidinate and vitamin B6 therapy. The controlled group accepted chemotherapy only. The clinical therapeutic effect, toxic reaction and life quality were compared between the two groups after two cycles of chemotherapy. Result:The effective rate of the treatment group and controlled group were 54.29% and 24.27% respectively (P<0.05). The improvement rate of life quality of the treatment group was higher than that of the controlled group ( P < 0.05). The toxic reaction of the treatment group was lower than that of the controlled group (P < 0.05 ). Conclusion ; Sodium cantharidinate and vitamin B6 injection combined with chemotherapy had a good effect on advanced non-small cell lung cancer patients and could improve the quality of life and reduce drug adverse reaction.%目的:评价斑蝥酸钠维生素B6注射液联合化疗治疗晚期非小细胞肺癌的临床疗效及不良反应.方法:将68例晚期非小细胞肺癌患者随机分为两组,治疗组(35例)给予斑蝥酸钠维生素B6注射液25 ml,同时进行多西紫衫醇联合奈达铂化疗,对照组(33例)予单纯联合化疗.治疗2周期后评价两组的疗效、毒副反应及生活质量改变.结果:治疗组、对照组的有效率分别为54.29%和24.27%(P<0.05).治疗组患者生活质量提高率高于对照组(P<0.05),毒性反应小于对照组(P<0.05).结论:斑蝥酸钠维生素B6注射液联合化疗治疗晚期非小细胞肺癌可提高临床疗效,改善患者的生活质量,同时可减少化疗毒副反应.

  11. Toxicity Reducing and Efficacy Enhancing Effect of Sodium Cantharidinate Vitamin B6 Injection on GP Chemotherapy Regimen in Treatment of Advanced Non-Small Cell Lung Carcinoma%斑蝥酸钠维生素B6注射液对GP方案治疗晚期非小细胞肺癌减毒增效作用观察

    Institute of Scientific and Technical Information of China (English)

    曹晶杰; 宋一雪; 蒋潮涌

    2013-01-01

    Objective To observe the efficacy and the influence on the immune function and analgesic effect of Sodium Cantharidinate and Vitamin B6 Injection in treating advanced non-small cell lung carcinoma (NSCLC) patients combined with GP chemotherapy. Methods Totally 79 patients with advanced NSCLC were randomly divided into the observation group and the control group. The observation group accepted GP chemotherapy plus Sodium Cantharidinate and Vitamin B6 Injection, and the control group was treated with GP chemotherapy. After 2 cycles of chemotherapy, the efficacy was evaluated, cellular immune function index and analgesic effect were observed. Results The objective response rate (RR) of the treatment group was 72.50%(29/40), and the control group was 48.72%(19/39). There was no significant difference between the two groups (P>0.05). After 2 cycles of treatment, the ratio of CD3+, CD4+, CD8+, CD4+/CD8+ and NK in the observation group were higher than the control group, with significant differences (P<0.05). The pain relief rate in the observation group was 75.00%(30/40), and it was 51.28%(20/39) in the control group, the difference was significant between the two groups (P<0.05). Conclusion Sodium Cantharidinate and Vitamin B6 Injection combined with GP chemotherapy can improve the short-term effect rate and the cellular immune function. It can also relieve the pain and improve the guality of life of patients with advanced NSCLC.%目的观察斑蝥酸钠维生素B6注射液对接受GP方案(吉西他滨+顺铂)治疗的晚期非小细胞肺癌(NSCLC)患者临床疗效、免疫功能及止痛效果的影响。方法将79例晚期NSCLC患者分为观察组和对照组,2组患者均给予GP方案化疗,同时观察组予斑蝥酸钠维生素B6注射液治疗,疗程为2个周期。评价2组近期疗效,对比免疫功能,并评估止痛效果。结果观察组的客观缓解率为72.50%(29/40),对照组为48.72%(19/39),差异有统计学意义(P<0.05)

  12. Disodium Cantharidinate and Vitamin B6 Combined with Tegafur,Gimeracil and Oteracil Potassium for Treating Stage IV Pancreatic Cancer in 27 Cases%斑蝥酸钠维生素B6联合替吉奥治疗Ⅳ期胰腺癌27例

    Institute of Scientific and Technical Information of China (English)

    关丽云; 马静; 袁世发; 曲金荣

    2015-01-01

    Objective To observe the clinical effect of Disodium Cantharidinate and Vitamin B6 combined with tegafur,gimeracil and oteracil potassium for treating advanced pancreatic cancer.Methods Totally 54 patients with advanced pancreatic cancer were divided into the treatment group and the control group according to the random number method,27 cases in each group.The control group was given and tegafur,gimeracil oteracil potassium,while the treatment group was given Disodium Cantharidinate and Vitamin B6.The short-term effect,clinical effect and adverse reactions were evaluated after 2 courses.Results The total effective rate and the disease control rate in the treatment group was 1 1.1 1%,59.26% respectively,and 7.41%,55.56% in the control group respectively,the difference had no statistical significance(P >0.05);the adverse reavtion rate of leukopenia,abnormal liver function,nausea and vomiting in the treatment group was significantly lower than those in the control group (P <0.05);the total effective rate of KPS score was 81.48%, which was significantly higher than 59.26% in the control group(P <0.05).Conclusion Disodium Cantharidinate and Vitamin B6 can reduce the toxic and side effect caused by tegafur,gimeracil and oteracil potassium,improve the quality of life,and is worth of clinical promotion.%目的:观察斑蝥酸钠维生素B6注射液联合替吉奥胶囊治疗晚期胰腺癌的临床疗效。方法将54例晚期胰腺癌患者按随机数字表法分为治疗组和对照组,各27例。对照组患者采用替吉奥胶囊治疗,治疗组患者在此基础上加用斑螫酸钠维生素B6注射液治疗。治疗2个周期后,评价两组患者的近期疗效、临床效果及不良反应。结果治疗组总有效率和疾病控制率分别为11.11%和59.26%,对照组分别为7.41%和55.56%,组间比较,差异无统计学意义(P>0.05);治疗组不良反应发生率低于对照组(P<0.05),特别是白细胞减

  13. Disodium Cantharidinate and Vitamin B6 Injection plus Chemotherapy for Non-Small Cell Lung Cancer: A Systematic Review%斑蝥酸钠维生素B6注射液联合化疗治疗非小细胞肺癌的系统评价

    Institute of Scientific and Technical Information of China (English)

    盛蕾; 李岩; 陈健鹏

    2012-01-01

    目的 系统评价斑蝥酸钠维生素B6注射液联合化疗治疗非小细胞肺癌( Non-small cell lung carcinoma,NSCLC)的有效性及安全性.方法 计算机检索Cochrane图书馆临床对照试验资料库、MEDLINE、EMbase、CBM、CNKI、VIP等数据库,检索时限为从1966年至2011年11月,纳入斑蝥酸钠维生素B6注射液联合化疗治疗NSCLC的随机对照试验.由2名评价者独立评价并交叉核对纳入研究质量后,对同质研究采用RevMan 5.1软件进行Meta分析.结果 经筛选,最终纳入8个RCT,共539例受试者.文献质量评价结果显示,8篇均为B级.Meta分析结果表明:与对照组相比,斑蝥酸钠维生素B6注射液能提高NSCLC化疗的有效率[RR=1.32,95%CI( 1.07,1.62)]、临床受益率[RR=1.24,95%CI (1.12,1.37)],改善患者生活质量[RR=2.23,95%CI( 1.55,3.19)]、临床症状[RR=1.55,95%CI( 1.24,1.95)],增加患者体重[RR=2.72,95%CI (1.74,4.25)],并减轻骨髓抑制毒性作用(白细胞下降率)[RR=0.36,95%CI (0.21,0.61)].结论 斑蝥酸钠维生素B6注射液对NSCLC患者接受化疗能起到增效减毒作用.为获得更佳的循证医学证据,建议开展更多大样本、多中心、长期随访的高质量临床随机对照试验.%Objective To systematically evaluate the effectiveness and safety of disodium cantharidinate and vita-rain B6 injection plus chemotherapy compared with chemotherapy alone, in the treatment of non-small cell lung cancer (NSCLC). Methods The Cochrane Library (Issue 1, 2011), MEDLINE (1966 to November 2011), EMbase (1984 to November 2011), CBM (1978 to November 2011), CNKI (1995 to November 2011) and VIP (1989 to November 2011) were searched electronically, and the randomized controlled trials (RCTs) about disodium cantharidinate and vitamin B6 injection plus chemotherapy for NSCLC were included. The quality of the included studies was assessed and crosschecked by two reviewers independently, and meta-analyses were performed for homogeneous

  14. Impact of cantharidin sodium vitamin B6 on serum tumor necrosis factor-α and interleukin-12 in non-small cell lung cancer patients%斑蝥酸钠维生素B6对非小细胞肺癌患者血清肿瘤坏死因子-α和白介素-12的影响

    Institute of Scientific and Technical Information of China (English)

    张晓笑; 梁斌鑫; 张婉珠; 赵瑜

    2015-01-01

    Objective To investigate the relationship between level of serum tumor necrosis factorα (TNF-α) and interleukin-12 (IL-12) and the antitumor effects of cantharidin sodium vitamin B6.Methods Forty advanced non-small cell lung cancer patients aged 30 to 80 were divided into experimental groups [paclitaxel + cisplatin (TP program) and sodium cantharidate vitamin B6] and control group (only TP program).Peripheral blood was drawn in the day of admission and the seventh day,the level of serum TNF-α and IL-12 were detected by method of enzyme-linked immunosorbent assay (ELISA),the results were analyzed.The World Health Organization (WHO) anticancer drugs in acute and subacute toxicity grading criteria were used to grade the chemotherapy side effects.Results The level of serum TNF-α and IL-12 were no significant difference on admission.After chemotherapy,serum TNF-α and IL-12 of experimental group was significantly higher than control group (P < 0.000 and P < 0.037,respectively).The serum TNF-α and IL-12 of experimental group had upward trend after chemotherapy.After 3 months of treatment,the remission rate was 85.7% in experimental group,significantly higher than 57.8% in the control group (P < 0.05).White blood cells,and platelets decrease in the experimental group were significantly reduced than the control group (P < 0.001 and P < 0.009,respectively),and there are no significant difference in nausea and vomiting reaction between experimental and control groups.Conclusions The antitumor effects of cantharidin sodium vitamin B6 might be related to the high level of serum TNF-α and IL-12,cantharidin sodium vitamin B6 in combination with chemotherapy in patients can reduce white blood cell and platelet decline after chemotherapy.%目的 探讨斑蝥酸钠维生素B6的抗肿瘤作用是否与非小细胞肺癌患者血清肿瘤坏死因子-α(TNF-α)和白介素-12(IL-12)水平有关.方法 随机将40例30 ~ 80岁的晚期非小细胞肺癌患者

  15. Effect of cantharidin on cell membrane integrity and potential in Spodoptera frugiperda Sf9 cells%斑蝥素对草地贪夜蛾Sf9细胞膜完整性和膜电位的影响

    Institute of Scientific and Technical Information of China (English)

    汪丽; 张来喜; 张志勇; 杨宝东; 王进忠; 张爱环; 张民照

    2013-01-01

    为明确斑蝥素对昆虫细胞膜的作用及其机理,本研究利用草地贪夜蛾Spodoptera frugiperda的卵巢细胞系Sf9细胞作为实验材料,采用透射电子显微技术(transmission electron microscope,TEM)、激光共聚焦显微镜(laser scanning confocal microscope,LSCM)结合荧光探针FDA/PI及DiBAC4 (3)技术研究斑蝥素(cantharidin,CTD)对Sf9 细胞膜完整性及膜电位(membrane potential,MP)的影响.结果表明:32 μmol/L CTD处理6h和12 h后,电镜观察均未发现细胞膜结构破损;FDA/PI染色后,32 μmol/L CTD处理0.5h后细胞FDA荧光强度比对照显著降低(P<0.05),碘化丙啶(propidium iodide,PI)染色的细胞比例与对照无显著性差异(P≥0.05).32 μmol/L CTD处理140 s后即引起MP发生显著性去极化(P<0.05);64μmol/L CTD处理瞬时MP发生显著性去极化(P<0.05);32 μmol/LCTD处理3h内及64 μmol/L CTD处理2h内MP仍保持显著性去极化(P<0.05),之后去极化程度降低;32 μmol/L CTD处理6h及64μmok/L CTD处理3h时MP去极化与对照组相比已无显著性差异(P≥0.05).结果说明,CTD处理短时间内可引起Sf9细胞膜电位去极化并维持一段时间,同时导致细胞活性发生不可逆下降,但未对细胞膜结构完整性产生破坏.%To investigate the effect of cantharidin (CTD) on insect cell membrane and its mechanism,the cell membrane integrity and potential in Spodoptera frugiperda Sf9 cells treated with CTD were tested by transmission electron microscope (TEM) and laser scanning confocal microscope (LSCM) combined with fluorescent dyes FDA/PI and DiBAC4 (3).The results showed that after the Sf9 cells were treated with 32 μmol/L CTD,their membrane structure was not disrupted at 6 h and 12 h after treatment,respectively.The FDA fluorescence intensities of the treated cells evidently declined compared with the control (P < 0.05) while the proportion of the PI-staining cells was not significantly different from that of the control (P≥0

  16. 芫菁寄生菌降解斑蝥素%Biodegradation of cantharidin by parasitic fungus of Meloidae

    Institute of Scientific and Technical Information of China (English)

    李晓飞; 陈祥盛; 侯晓晖

    2008-01-01

    选用2种芫菁的寄生菌--球孢白僵菌Beauveria bassiana和曲霉Aspergillus sp.,进行斑蝥素的抑菌试验和对斑蝥素的降解试验.结果表明:斑蝥素对这2种真菌没有抑制作用.球孢白僵菌可以有效地降解斑蝥素,降解率为90.45%,而曲霉不能降解斑蝥素.

  17. Research on the role of natural cantharidin to trichomonas vaginalis%天然产物斑蝥素对阴道毛滴虫作用的研究

    Institute of Scientific and Technical Information of China (English)

    李晓飞

    2013-01-01

    目的 体外观察斑蝥素对8 株抗甲硝唑阴道毛滴虫的杀灭效果及安全性.方法 以斑蝥素终质量浓度为15.313~490.000 μg/mL 作用于体外培养的阴道毛滴虫.结果 30.625 μg/mL 为斑蝥素体外杀灭阴道毛滴虫的最低有效质量浓度.结论 斑蝥素对体外阴道毛滴虫有杀灭效果.

  18. 斑蝥素与去甲斑蝥素对昆虫细胞Sf9抑制作用比较%Comparisons of inhibition between cantharidin and norcantharidin on Sf9 cells

    Institute of Scientific and Technical Information of China (English)

    周晗颖; 杨宝东; 张民照; 王进忠; 张爱环; 张志勇

    2012-01-01

    为探索斑蝥素的类似物去甲斑蝥素对昆虫的毒杀机理,本研究利用草地贪夜蛾Spodoptera frugiperda卵巢细胞系Sf9细胞作为实验材料,采用CCK -8法和AO/EB荧光染色法比较了斑蝥素(CTD)和去甲斑蝥素(NCTD)对细胞的增殖抑制和抑制方式.结果显示,3.125 μg/mL的CTD处理细胞抑制率6h为20.00±1.10%,24 h为66.33 ±0.81%;50 μg/mL的CTD处理细胞抑制率6h为42.69±6.34%,24 h为74.60±1.51%.3.125 μg/mL的NCTD处理细胞抑制率6h为10.03±1.72%,24 h为21.75±6.22%;50 μg/mL的NCTD处理细胞抑制率6h为40.79±1.32%,24 h为66.08±3.32%.结果表明,CTD与NCTD均能有效抑制Sf9细胞增殖和诱导细胞凋亡,且抑制率呈现出时间、剂量依赖性,较高剂量NCTD可以替代CTD达到相同效果.%To investigate the mechanism of NCTD's toxic effect on Sf9 cells, CCK -8 assay and AO/EB fluorescent dyes were used to detect the inhibition rates and the way of function. There results showed that, treated with CTD of 3. 125 g/mL after 6 hour and 24 hour, the inhibition rates of test cells were 20. 00 ± 1. 10% and 66. 33 ±0. 81% ; treated with CTD of 50 g/mL after 6 hour and 24 hour, the inhibition rates of test cells were 42. 69 ±6. 34% and 74. 60 ± 1. 51% . Treated with NCTD of 3. 125 g/mL after 6 hour and 24 hour, the inhibition rates of test cells were 10. 03 ± 1. 72% and 21. 75 ±6. 22% ; treated with NCTD of 50 g/mL after 6 hour and 24 hour, the inhibition rates of test cells were 40. 79 ± 1.32% and 66. 08 ±3.32%. It was indicated that, both of CTD and NCTD could effectively inhibit cell's proliferation in concentration-dependent and time-dependent, higher concentration of NCTD could replace lower concentration of CTD to reach similar inhibition rates, and NCTD could induce apoptosis significantly as well as CTD.

  19. 去甲斑蝥素-泊洛沙姆聚合物纳米胶束的制备及表征%Preparation and Characterization of Norepinephrine Cantharidin-Poloxamer Polymer Nano-Micelle

    Institute of Scientific and Technical Information of China (English)

    尹美珍; 杨子春; 包洋; 苷珺; 蔡江红

    2015-01-01

    为制备去甲斑蝥素-泊洛沙姆给药系统新制剂,采用薄膜水化法,以泊洛沙姆F127为载体,包载去甲斑蝥素,制备纳米聚合物载药胶束;高效液相色谱法测定胶束的包封率和载药量,动态光散射法测定胶束粒径,紫外分光光度仪以及红外分光光度仪测定并分析药物在胶束中的分布状态. 结果显示去甲斑蝥素被成功包载于聚合物胶束上,聚合物载药胶束的平均粒径为10. 3 nm,粒度分布较窄,包封率和载药量分别约为98%和4 . 67%. 因此,这种载药纳米粒制备工艺简单,粒径小,对疏水性药物有较高的包封率. 这为进一步制备靶向纳米载药胶束打下了基础,为包载其他疏水药物的聚合物胶束的制备提供实验依据.%To prepare a new form of norcantharidin-poloxamer nano-drug delivery systems,a thin-film hy-dration method was used,norcantharidin -loaded polymeric micelles with poloxamer F127 as a novel drug carrier was prepared. Eencapsulation ratio and drug-loading coeffieient,particle size,and drug distribution state of the polymeric micelles were examined by means of HPLC,dynamic light scattering,UV spectrum and FTIR spectrum respectively. The results showed that norcantharidin was successfully entrapped in the polymer micelles with encapsulation ratio of 98%. The drug-loaded polymeric micelles possessed narrow particle size distribution with average particle size of 10. 3 nm,and drug-loading coeffieient of 4. 67%. Therefore,this drug-loaded nanoparticles possess several advantages:simple preparation process, small particle size, and high encapsulation efficiency for hydrophobic drugs. This will set the stage for the further preparation of targe-ted nanoparticles,but also for the preparation of other drug-loaded polymeric micelles offer experimental ba-sis.

  20. 天然源农药0.1%斑蝥素水溶剂的应用技术%Study on Applied Techniques of Natural Watery Pesticide 0.1% Cantharidin

    Institute of Scientific and Technical Information of China (English)

    刁绍东; 王菁; 顾明洁; 姜红霞; 周生久

    2003-01-01

    报道了天然源农药0.1%斑螫素水溶剂的应用技术可行性研究,结果表明,0.1%斑蝥素水溶剂200~250g a.i./hm2,可有效的控制菜蚜、菜青虫、桃蚜、梨二叉蚜等害虫的为害,对小菜蛾具有一定作用,对作物无毒害影响.

  1. Effects of Cantharidin on Insect Cell Spex-Ⅶ and Sf9%斑蝥素对昆虫细胞Spex-Ⅶ和Sf9的作用效果

    Institute of Scientific and Technical Information of China (English)

    陈利平; 杨宝东; 张志勇; 王进忠; 孙淑玲

    2008-01-01

    以昆虫细胞Spex-Ⅷ和Sf9为试材研究斑蝥素对昆虫的杀虫机理.采用MTT法,结果表明,斑蝥素对这两种细胞凋亡的增殖有剂量和时间依赖性抑制作用,且对Sf9作用更为敏感:处理2,3,4 d后,斑蝥素对Spex-Ⅶ细胞的抑制中浓度(IC50)分别为17.623 8,13.225 1,10.707 8μg/mL;对Sf9细胞的IC50为5.433 8,1.228 9,1.222 6μg/mL;采用瑞氏-吉姆萨细胞染色和Hoechst33258荧光细胞染色法,结果表明12.5μg/mL斑蝥素处理Sf9细胞,25μg/mL和50μg/mL斑蝥素处理Spex-Ⅶ细胞,2 d后,斑蝥素对两种细胞有诱导凋亡的作用.可以观察到凋亡形态特征:胞膜完整,染色质固缩,核碎裂,凋亡小体形成.

  2. Molluscum contagiosum

    Science.gov (United States)

    ... lesions may result in scarring. Medicines, such as salicylic acid preparations used to remove warts , may be helpful. But these medicines can cause blistering that leads to temporary skin discoloration. Cantharidin, commonly called beetle juice, is the ...

  3. Cantharidin patches and intravenous administration of vitamin C in the concomitant treatment of herpes zoster:a case report%斑蝥素贴剂结合维生素C静脉注射辅助治疗带状疱疹1例

    Institute of Scientific and Technical Information of China (English)

    Martin Schencking; Karin Kraft

    2011-01-01

    @@ The diagnosis and therapy for herpes zoster (HZ) are frequently associated with consultation of a general practitioner and with hospital care.Although there are several serious complications of zoster such as ophthalmic, splanchnic, cerebral,and motor conditions, the most common and feared in immunocompetent adults is postherpetic neuralgia (PHN).Its definition is controversial.Recent data support the distinction between acute herpetic neuralgia (within 30 d of rash onset),subacute herpetic neuralgia (30 to 120 d after rash onset), and postherpetic neuralgia (defined as pain lasting at least 120 d from rash onset)[1-3].PHN is classified as a neuropathic pain that is associated with mechanical allodynia where normally innocuous tactile stimuli are perceived as painful[2].In actual studies it is reported that the incidence of HZ is 3.2 to 4.1 in 1 000 person-years[4, 5].

  4. 斑蝥素对草地贪夜蛾卵巢细胞凋亡基因PP2A表达的影响%The Effects of Cantharidin on the PP2A Gene Expression in the Ovarian Cell of Spodoptera frugiperda

    Institute of Scientific and Technical Information of China (English)

    张民照; 杜艳丽; 郝少东; 覃晓春; 王进忠; 张志勇

    2014-01-01

    用实时荧光定量PCR技术对草地贪夜蛾Spodoptera frugiperda卵巢组织细胞蛋白磷酸酶2A(protein phosphatase 2A,PP2A)基因表达进行分析以研究斑蝥素对其表达的影响.结果表明,PP2A相对表达量与斑蝥素浓度存在不显著的负相关性,斑蝥素各浓度下PP2A相对表达量差异都不显著(P<0.05),处理24h后对照的极显著高于用斑蝥素处理的(P<0.01).在相同斑蝥素浓度下,除25μg/mL外其他浓度处理24 h后PP2A相对定量显著高于6h的(P<0.05).研究结果说明,斑蝥素处理对卵巢细胞内的PP2A基因相对表达量有一定的影响,且与斑蝥素的浓度和处理时间有一定关系.

  5. 基因芯片技术分析斑蝥素对肝癌细胞细胞毒作用的分子机制%Gene microarrays in detecting molecular mechanisms of cantharidin-mediated cytotoxicity on human hepatic cancer cells

    Institute of Scientific and Technical Information of China (English)

    胡和平; 张俊平; 应康; 肖振宇; 吴红梅; 毛裕民; 吴孟超

    2003-01-01

    目的:研究抗癌药斑蝥素对肝癌细胞细胞毒作用的分子机制.方法:应用基因芯片技术检测12.5 μmol/L斑蝥素作用于肝癌QGY7703细胞24 h后基因表达谱的变化.结果:斑蝥素抑制细胞表达参与细胞周期进程基因(如p27、ref-1、DNA polymerase delta、XRCC9等)、能量代谢基因(如malate dehydrogenase、ADP/ATP translocase等)、致瘤活性基因(如c-myc、tre等)以及肿瘤特异表达基因(如bladder cancer related protein等).相反,斑蝥素促进了多种细胞生长抑制基因(如BCRA2、BTG2、dual-specificity protein phosphatase等)以及凋亡相关基因(如ATL-derived PMA-responsive peptide等)的表达.结论:斑蝥素改变调控细胞周期进程、细胞增殖、能量代谢以及凋亡级联反应的基因表达可能是其细胞毒作用的机制.

  6. 斑蝥素通过MAPK途径对肺癌A549细胞周期阻滞及其分子机制的研究%Role and molecular mechanism of cantharidin in cell cycle arrest of A549 human lung carcinoma cells through mitogen-activated protein kinase pathway

    Institute of Scientific and Technical Information of China (English)

    张卫东; 赵惠儒; 于秉治; 王晓华; 宗志红; 刘莹

    2006-01-01

    目的:探讨斑蝥素对人肺癌A549细胞的周期阻滞作用及其分子机制.方法:采用MTT法检测斑蝥素对A549细胞的增殖抑制作用;流式细胞仪检测细胞周期;以蛋白印迹法分析斑蝥素作用后细胞周期蛋白B1(cyclinB1)、p34cdc2、phos-p34cdc2、p21、survivin、ERK1/ERK2、phos-ERK1/phos-ERK2等蛋白表达或活性的改变.结果:斑蝥素能抑制A549细胞的增殖;斑蝥素作用于A549细胞后引起G2/M期阻滞;斑蝥素处理后,p34cdc2、phos-p34cdc2表达量没有改变,cyclinB1、survivin蛋白表达量减少,p21蛋白表达量增加.ERK1/ERK2、phos-ERK1/phos-ERK2表达量降低.结论:斑蝥素通过调节cyclinB1、p21、survivin、ERK1/ERK2、phos-ERK1/phos-ERK2等蛋白表达或活性的改变引起G2/M期阻滞.

  7. [Blister beetle dermatitis: Dermatitis linearis].

    Science.gov (United States)

    Dieterle, R; Faulde, M; Erkens, K

    2015-05-01

    Several families of beetles cause toxic reactions on exposed human skin. Cantharidin provokes nearly asymptomatic vesicles and blisters, while pederin leads to itching and burning erythema with vesicles and small pustules, later crusts. Paederi are attracted by fluorescent light especially after rain showers and cause outbreaks in regions with moderate climate. Clinical findings and patient history lead to the diagnosis: dermatitis linearis.

  8. Environ: E00532 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available E00532 Tiger beetle Mylabris Crude drug Cantharidin [CPD:C16778], Fat Mylabris sida...e, Mylabris cichorii [TAX:580878], Mylabris [TAX:268452] Meloidae Mylabris sidae, Mylabris cichorii (dried) Crude drugs [BR:br08305] Animals Insects E00532 Tiger beetle ...

  9. Study on the Renal Anemia: Experimental Study in Acute Renal Anemia

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Zo Eun [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    1969-09-15

    The double tracer study on erythrokinetics was carried out experimentally with radioactive iron({sup 59}Fe) and chromium ({sup 51}Cr) in rabbits. The 0.1% cantharidin solution and 1% pot. perchlomate solution was given subcutaneously to 20 rabbits respectively. 3 and 6 days after injection, the blood chemistry, urine examination, ferrokinetics and apparent half survival time of RBC were ({sup 51}Cr T-1/2) determined. Following were the results: 1) Red blood cell hematocrit and hemoglobin values were moderately reduced and B.U.N. and serum creatinine values were slightly increased in the cantharidin group, while B.U.N. and serum creatinine values were within normal limits in the pot. perchlomate group. Reticulocyte values were slightly increased in the cantharidin group, while was normal range in the pot. perchlomate group. 2) Blood chemistry finding was not significant statistically in both experimental groups, but serum iron value was moderately reduced in both group. 3) Plasma volume was unchanged in both group, but red cell volume and whole blood volume were slightly reduced in both groups. 4) Results of ferrokinetics were as follows: i) The plasma iron disappearance rate was delayed in both groups. Plasma iron turnover rate, red cell iron utilization and red cell iron turnover rate were decreased in both groups, and then red cell iron turnover rate was more decreased than plasma iron turnover rate in both groups. Circulating red cell iron was slightly increased in cantharidin group and red cell iron concentration was within normal range in both groups. ii) P.I.T.R.-R.C.I.T. value moderately increased in the cantharidin group and slightly increased in the pot. perchlomate group. Reticulocyte index, red cell iron turnover index, plasma iron turnover index and effective erythropoiesis index were wholly reduced in both groups. iii) The red cell life span was slightly shortened in the cantharidin group while was within normal range in pot. perchlomate group. The

  10. Apoptosis induced by norcantharidin in human tumor cells

    Institute of Scientific and Technical Information of China (English)

    Zhen Xiao Sun; Qing Wen Ma; Tian De Zhao; Yu Lin Wei; Guang Sheng Wang; Jia Shi Li

    2000-01-01

    @@INTRODUCTION The antitumor activity of norcantharidin (NCTD),the demethylated analogue of cantharidin, was studied in the early 1980s in China. NCTD has no side effects on urinary organs which cantharidin has shown and is easier to synthesize, and it can inhibit the proliferation of several tumor cell lines as well as transplanted tumors. Clinical trials with NCTD as a monotherapeutic agent indicated that NCTD had beneficial effects in patients with different kinds of digestive tract cancers, such as primary hepatoma,carcinomas of esophagus and gastric cancer, but no depressive effect on bone marrow cells. NCTD can increase the white blood cell count by stimulating the bone marrow and has some antagonistic effect against leukopenia caused by other agents. The exact cellular and molecular mechanisms of NCTD on tumor cells have not yet been elucidated to date[1-3].

  11. Transgenic plant cells lacking mitochondrial alternative oxidase have increased susceptibility to mitochondria-dependent and -independent pathways of programmed cell death.

    Science.gov (United States)

    Robson, Christine A; Vanlerberghe, Greg C

    2002-08-01

    The plant mitochondrial electron transport chain is branched such that electrons at ubiquinol can be diverted to oxygen via the alternative oxidase (AOX). This pathway does not contribute to ATP synthesis but can dampen the mitochondrial generation of reactive oxygen species. Here, we establish that transgenic tobacco (Nicotiana tabacum L. cv Petit Havana SR1) cells lacking AOX (AS8 cells) show increased susceptibility to three different death-inducing compounds (H(2)O(2), salicylic acid [SA], and the protein phosphatase inhibitor cantharidin) in comparison with wild-type cells. The timing and extent of AS8 cell death are very similar among the three treatments and, in each case, are accompanied by the accumulation of oligonucleosomal fragments of DNA, indicative of programmed cell death. Death induced by H(2)O(2) or SA occurs by a mitochondria-dependent pathway characterized by cytochrome c release from the mitochondrion. Conversely, death induced by cantharidin occurs by a pathway without any obvious mitochondrial involvement. The ability of AOX to attenuate these death pathways may relate to its ability to maintain mitochondrial function after insult with a death-inducing compound or may relate to its ability to prevent chronic oxidative stress within the mitochondrion. In support of the latter, long-term treatment of AS8 cells with an antioxidant compound increased the resistance of AS8 cells to SA- or cantharidin-induced death. The results indicate that plants maintain both mitochondria-dependent and -independent pathways of programmed cell death and that AOX may act as an important mitochondrial "survival protein" against such death.

  12. Synthesis and Biological Evaluation of Norcantharidin Derivatives Possessing an Aromatic Amine Moiety as Antifungal Agents

    Directory of Open Access Journals (Sweden)

    Yang Wang

    2015-12-01

    Full Text Available Based on the structure of naturally produced cantharidin, different arylamine groups were linked to the norcantharidin scaffold to provide thirty six compounds. Their structures were confirmed by melting point, 1H-NMR, 13C-NMR and HRMS-ESI studies. These synthetic compounds were tested as fungistatic agents against eight phytopathogenic fungi using the mycelium growth rate method. Of these thirty six derivatives, seven displayed stronger antifungal activity than did norcantharidin, seven showed higher activity than did cantharidin and three exhibited more significant activity than that of thiabendazole. In particular, 3-(3′-chloro-phenylcarbamoyl norcantharidate II-8 showed the most significant fungicidal activity against Sclerotinia fructigena and S. sclerotiorum, with IC50 values of 0.88 and 0.97 μg/mL, respectively. The preliminary structure-activity relationship data of these compounds revealed that: (1 the benzene ring is critical for the improvement of the spectrum of antifungal activity (3-phenylcarbamoyl norcantharidate II-1 vs norcantharidin and cantharidin; (2 among the three sites, including the C-2′, C-3′ and C-4′ positions of the phenyl ring, the presence of a halogen atom at the C-3′position of the benzene ring caused the most significant increase in antifungal activity; (3 compounds with strongly electron-drawing or electron-donating groups substitutions were found to have a poor antifungal activity; and (4 compared with fluorine, bromine and iodine, chlorine substituted at the C-3′ position of the benzene ring most greatly promoted fungistatic activity. Thus, compound II-8 has emerged as new lead structure for the development of new fungicides.

  13. A Comparison of Human Neutrophils Acquired from Four Experimental Models of Inflammation

    Science.gov (United States)

    Motwani, Madhur P.; Day, Richard M.; Gilroy, Derek W.; O’Brien, Alastair J.

    2016-01-01

    Defects in neutrophil function have been implicated in a wide spectrum of clinical conditions. Several models are employed to study activated human neutrophils akin to those found at a site of inflammation. These include whole blood (WB) ex vivo stimulation with lipopolysaccharide (LPS) and in vivo techniques: cantharidin blister, skin windows and intra-dermal injection of UV-killed E.coli (UVKEc). Neutrophils obtained from these have never been compared. We compared the activation status of neutrophils from each technique in order to inform the optimal model for use in human studies. Healthy male volunteers were randomised to undergo one of the four techniques (n = 5/group). LPS: WB stimulated with 1ng/ml of LPS for 4 hours. Cantharidin: 12.5μl of 0.1% cantharidin elicited a single blister, aspirated at 24 hours. Skin windows: four 6mm mechanical-suction blisters created, de-roofed and an exudate-collection chamber placed over the windows for 4 hours before aspiration. UVKEc: 1.5 x 107 UVKEc injected intra-dermally. A single 10mm mechanical-suction blister formed and aspirated at 4 hours. Unstimulated WB used as the control. Flow cytometry was used to determine activation status using CD16, CD11b, CD54, CD62L and CD88. Functional status was assessed with a phagocytosis assay. The pattern of neutrophil activation was similar in all models. Neutrophil CD11b was elevated in all models, most markedly in UVKEc (p<0.0001), and CD54 was also elevated but only significant in the LPS model (p = 0.001). CD62L was significantly reduced in all 4 models (p<0.0001) and CD88 was also suppressed in all. There were no changes in CD16 in any model, neither was there any significant difference in the phagocytic capacity of the neutrophils. In summary, there are no significant differences in activation marker expression or phagocytic capacity in the neutrophils obtained from each technique. Therefore we believe whole blood stimulation is the best model in experimentally challenging

  14. Oedemerid blister beetle dermatosis: a review.

    Science.gov (United States)

    Nicholls, D S; Christmas, T I; Greig, D E

    1990-05-01

    Blister beetle dermatosis is a distinctive vesiculobullous eruption that occurs after contact with three major groups of beetles (Order: Coleoptera). It is caused by a vesicant chemical contained in the body fluids of the beetles. The smallest and least known family is the Oedemeridae. Although there are few references in the medical literature, blister beetle dermatosis caused by oedemerids may be more common and widespread than currently recognized. The best known family is the Meloidae with numerous species worldwide causing blistering. The vesicant chemical in both Oedemeridae and Meloidae is cantharidin. The third group of blister beetles includes species of the genus Paederus (Family: Staphylinidae). The clinicopathologic picture differs because this genus contains a different vesicant agent, pederin. The clinicopathologic features of oedemerid blister beetle dermatosis are described. The world medical and relevant entomologic literature is reviewed.

  15. Advancements in Pharmacotherapy for Noncancerous Manifestations of HPV

    Directory of Open Access Journals (Sweden)

    Ramya Kollipara

    2015-04-01

    Full Text Available Human papillomavirus (HPV is the most common sexually transmitted disease. Via infection of the basal epithelial cells, HPV causes numerous malignancies and noncancerous cutaneous manifestations. Noncancerous cutaneous manifestations of HPV, including common, plantar, plane, and anogenital warts, are among the most common reasons for an office visit. Although there are various therapies available, they are notoriously difficult to treat. HPV treatments can be grouped into destructive (cantharidin, salicylic acid, virucidal (cidofovir, interferon-α, antimitotic (bleomycin, podophyllotoxin, 5-fluorouracil, immunotherapy (Candida antigen, contact allergen immunotherapy, imiquimod or miscellaneous (trichloroacetic acid, polyphenon E. The mechanism of action, recent efficacy data, safety profile and recommended regimen for each of these treatment modalities is discussed.

  16. Aphrodisiacs past and present: a historical review.

    Science.gov (United States)

    Sandroni, P

    2001-10-01

    The drug Viagra (sildenafil) has drawn public attention to aphrodisiacs. The search for such substances dates back millennia. Aphrodisiacs can be classified by their mode of action into 3 types: those that increase (1) libido, (2) potency, or (3) sexual pleasure. Various substances of animal and plant origin have been used in folk medicines of different cultures; some have been identified pharmacologically, allowing for understanding of their mechanisms of action. For increasing libido, ambrein, a major constituent of Ambra grisea, is used in Arab countries. This tricyclic triterpene alcohol increases the concentration of several anterior pituitary hormones and serum testosterone. Bufo toad skin and glands contain bufotenine (and other bufadienolides), a putative hallucinogenic congener of serotonin. It is the active ingredient in West Indian "love stone" and the Chinese medication chan su. The aphrodisiac properties are likely of central origin, as are the other effects of the drug. For increasing potency, Panax ginseng used in traditional Chinese medicine, works as an antioxidant by enhancing nitric oxide synthesis in the endothelium of many organs, including the corpora cavernosa; ginsenosides also enhance acetylcholine-induced and transmural nerve stimulation-activated relaxation associated with increased tissue cyclic guanosine monophosphate, hence the aphrodisiac properties. For increasing sexual pleasure, cantharidin ("Spanish fly") is a chemical with vesicant properties derived from blister beetles, which have been used for millennia as a sexual stimulant. Its mode of action is by inhibition of phosphodiesterase and protein phosphatase activity and stimulation of beta-receptors, inducing vascular congestion and inflammation. Morbidity from its abuse is significant. The ingestion of live beetles (Palembus dermestoides) in Southeast Asia and triatomids in Mexico may have a basis similar to cantharidin. It is of paramount importance for the physician to be

  17. Evolution of the Macrophage CD163 Phenotype and Cytokine Profiles in a Human Model of Resolving Inflammation

    Directory of Open Access Journals (Sweden)

    Betsy J. Evans

    2013-01-01

    Full Text Available Cantharidin skin blisters were examined over two days to model the acute and resolving phases of inflammation in human skin. Four blisters were created by topical administration of cantharidin (0.1% v/v to the forearm of healthy volunteers, with IRB approval. Duplicate skin blisters were aspirated at 16 and 40 hours to model the proinflammatory and resolving phases, respectively. There was a significant increase in leukocyte infiltrate at 40 h with appearance of a “resolving macrophage” phenotype CD14+CD163+ by flow cytometry. Neutrophils acquired apoptotic markers at 40 h and were observed to be phagocytosed by macrophagic “Reiter’s” cells. Multiplex cytokine analysis demonstrated that monocyte chemoattractant protein (MCP-1/CCL2, interleukin- (IL- 6, IL-8/CXCL8, macrophage inflammatory protein (MIP1α/CCL3, MIP-1β/CCL4, tumor necrosis factor- (TNF- α, and eotaxin (CCL11 were all significantly upregulated at 16 h compared with 40 h. In contrast, immunoregulatory transforming growth factor- (TGF- β, macrophage-derived chemokine (MDC/CCL22, and interferon-inducible protein (IP-10/CXCL10 were significantly elevated at 40 h. Our results demonstrate that the phases of inflammation and resolution can be discriminated in a two-day model of dermal wound healing. This confirms and extends our understanding of wound repair in humans and provides a powerful research tool for use in clinical settings and to track the molecular benefits of therapeutic intervention.

  18. The RCN1-encoded A subunit of protein phosphatase 2A increases phosphatase activity in vivo

    Science.gov (United States)

    Deruere, J.; Jackson, K.; Garbers, C.; Soll, D.; Delong, A.; Evans, M. L. (Principal Investigator)

    1999-01-01

    Protein phosphatase 2A (PP2A), a heterotrimeric serine/threonine-specific protein phosphatase, comprises a catalytic C subunit and two distinct regulatory subunits, A and B. The RCN1 gene encodes one of three A regulatory subunits in Arabidopsis thaliana. A T-DNA insertion mutation at this locus impairs root curling, seedling organ elongation and apical hypocotyl hook formation. We have used in vivo and in vitro assays to gauge the impact of the rcn1 mutation on PP2A activity in seedlings. PP2A activity is decreased in extracts from rcn1 mutant seedlings, and this decrease is not due to a reduction in catalytic subunit expression. Roots of mutant seedlings exhibit increased sensitivity to the phosphatase inhibitors okadaic acid and cantharidin in organ elongation assays. Shoots of dark-grown, but not light-grown seedlings also show increased inhibitor sensitivity. Furthermore, cantharidin treatment of wild-type seedlings mimics the rcn1 defect in root curling, root waving and hypocotyl hook formation assays. In roots of wild-type seedlings, RCN1 mRNA is expressed at high levels in root tips, and accumulates to lower levels in the pericycle and lateral root primordia. In shoots, RCN1 is expressed in the apical hook and the basal, rapidly elongating cells in etiolated hypocotyls, and in the shoot meristem and leaf primordia of light-grown seedlings. Our results show that the wild-type RCN1-encoded A subunit functions as a positive regulator of the PP2A holoenzyme, increasing activity towards substrates involved in organ elongation and differential cell elongation responses such as root curling.

  19. Study on Quality Standard for Xiaoliu Capsule%消瘤胶囊的质量标准研究

    Institute of Scientific and Technical Information of China (English)

    顾和亚; 周琴妹; 梁海宁; 李悦予; 刘汉清

    2012-01-01

    Objective To establish the quality standard for Xiaoliu Capsule. Methods Codonopsis Radix, Salviae miltiorahizae Radix et Rhizoma and Sparganii Rhizoma Tuber were identified by TLC; HPLC method was used to determine the content of cantharidin. Results The TLC spots were quite clear;The calibration curve of cantharidin was linear within the range of 0.097 25 ~ 0.778 mg/mL,and the regression equation was A=630.5569C - 8.62857, (r=0.9999).Conclusion The method was simple, accurate and reproducible, and could be used for the quality control of Xiaoliu Capsule.%目的建立消瘤胶囊的质量标准.方法 采用薄层色谱法鉴别处方药材党参、丹参、三棱.采用高效液相色谱测定制剂中的斑蝥素含量.结果 薄层色谱鉴别在与对照药材相应的位置上,分别显相同颜色的斑点,方法专属性强,阴性对照无干扰.含量测定,斑蝥素的回归方程为:A=630.556 9C-8.628 57,r=).9999.浓度在0.097 25~0.778 mg/mL范围内线性关系良好.消瘤胶囊中斑蝥素含量拟控制在1.5%以上.结论 本方法简便、准确、重现性好,可用于消瘤胶囊的质量控制.

  20. Tattoo removal.

    Science.gov (United States)

    Adatto, Maurice A; Halachmi, Shlomit; Lapidoth, Moshe

    2011-01-01

    Over 50,000 new tattoos are placed each year in the United States. Studies estimate that 24% of American college students have tattoos and 10% of male American adults have a tattoo. The rising popularity of tattoos has spurred a corresponding increase in tattoo removal. Not all tattoos are placed intentionally or for aesthetic reasons though. Traumatic tattoos due to unintentional penetration of exogenous pigments can also occur, as well as the placement of medical tattoos to mark treatment boundaries, for example in radiation therapy. Protocols for tattoo removal have evolved over history. The first evidence of tattoo removal attempts was found in Egyptian mummies, dated to have lived 4,000 years BC. Ancient Greek writings describe tattoo removal with salt abrasion or with a paste containing cloves of white garlic mixed with Alexandrian cantharidin. With the advent of Q-switched lasers in the late 1960s, the outcomes of tattoo removal changed radically. In addition to their selective absorption by the pigment, the extremely short pulse duration of Q-switched lasers has made them the gold standard for tattoo removal.

  1. Genetic and chemical reductions in protein phosphatase activity alter auxin transport, gravity response, and lateral root growth

    Science.gov (United States)

    Rashotte, A. M.; DeLong, A.; Muday, G. K.; Brown, C. S. (Principal Investigator)

    2001-01-01

    Auxin transport is required for important growth and developmental processes in plants, including gravity response and lateral root growth. Several lines of evidence suggest that reversible protein phosphorylation regulates auxin transport. Arabidopsis rcn1 mutant seedlings exhibit reduced protein phosphatase 2A activity and defects in differential cell elongation. Here we report that reduced phosphatase activity alters auxin transport and dependent physiological processes in the seedling root. Root basipetal transport was increased in rcn1 or phosphatase inhibitor-treated seedlings but showed normal sensitivity to the auxin transport inhibitor naphthylphthalamic acid (NPA). Phosphatase inhibition reduced root gravity response and delayed the establishment of differential auxin-induced gene expression across a gravity-stimulated root tip. An NPA treatment that reduced basipetal transport in rcn1 and cantharidin-treated wild-type plants also restored a normal gravity response and asymmetric auxin-induced gene expression, indicating that increased basipetal auxin transport impedes gravitropism. Increased auxin transport in rcn1 or phosphatase inhibitor-treated seedlings did not require the AGR1/EIR1/PIN2/WAV6 or AUX1 gene products. In contrast to basipetal transport, root acropetal transport was normal in phosphatase-inhibited seedlings in the absence of NPA, although it showed reduced NPA sensitivity. Lateral root growth also exhibited reduced NPA sensitivity in rcn1 seedlings, consistent with acropetal transport controlling lateral root growth. These results support the role of protein phosphorylation in regulating auxin transport and suggest that the acropetal and basipetal auxin transport streams are differentially regulated.

  2. Influence of different oils on penetration of human hair by fungi.

    Science.gov (United States)

    Bahuguna, S; Kushwaha, R K

    1993-02-01

    Synopsis The hair perforating ability of Microsporum gypseum and Trichophyton vanbreuseghemii was tested in presence of seventeen oils. Clove, olive and turpentine oils were found to be fully inhibitory for hair penetration by both fungi. Hair segments smeared with cantheridine oil and keocarpin hair vitalizer failed to reveal any perforation by T. vanbreuseghemii whereas arnica and shikakai oils showed little perforation by this fungus. Résumé La capacité de pénétration du Microsporum gypseum et du Trichophyton vanbreuseghemii a été testée en présence de 17 huiles. Les huiles de clou de girofle, d'olive et de térébenthine se sont avérées complétement inhibitrices du pouvoir de pénétration des 2 levures sur les cheveux. Des cheveux frottés avec de l'huile de cantharidine et un produit vitalisant des cheveux à kéocarpine n'ont révélé aucune pénétration par le T. vanbreuseghemii alors que l'huile d'arnica et l'huile de shikakai ont favorisé une légère pénétration par cette levure.

  3. Pinoid kinase regulates root gravitropism through modulation of PIN2-dependent basipetal auxin transport in Arabidopsis thaliana

    Science.gov (United States)

    Muday, Gloria; Sukumar, Poornima; Edwards, Karin; Delong, Alison; Rahman, Abidur

    Reversible protein phosphorylation is a key regulatory mechanism governing polar auxin transport. We tested the hypothesis that PINOID (PID)-mediated phosphorylation and RCN1- regulated dephosphorylation might antagonistically regulate auxin transport and gravity response in seedling roots. Here we show that basipetal IAA transport and gravitropism are reduced in pid mutant seedlings, while acropetal transport and lateral root development are unchanged. Treatment of wild-type seedlings with the protein kinase inhibitor, staurosporine, phenocopied the reduced auxin transport and gravity response of pid-9 and reduced formation of asymmetric DR5-revGFP expression at the root tip after reorientation relative to gravity. Gravitropism and auxin transport in pid are resistant to further inhibition by staurosporine. Gravity response defects of rcn1 and pid-9 are partially rescued by treatment with staurosporine or the phosphatase inhibitor, cantharidin, respectively, and in the pid-9 rcn1 double mutant. Furthermore, the effect of staurosporine is lost in pin2, and a PIN2::GFP fusion protein accumulates in endomembrane compartments after staurosporine treatment. In the pid-9 mutant, immunological techniques find a similar PIN2 localization. These data suggest that staurosporine inhibits gravitropism and basipetal IAA transport by blocking PID action and altering PIN2 localization and support the model that PID and RCN1 reciprocally regulate root gravitropic curvature.

  4. Norcantharidin induced DU145 cell apoptosis through ROS-mediated mitochondrial dysfunction and energy depletion.

    Science.gov (United States)

    Shen, Bo; He, Pei-Jie; Shao, Chun-Lin

    2013-01-01

    Norcantharidin (NCTD), a demethylated analog of cantharidin derived from blister beetles, has attracted considerable attentions in recent years due to their definitely toxic properties and the noteworthy advantages in stimulating bone marrow and increasing the peripheral leukocytes. Hence, it is worth studying the anti-tumor effect of NCTD on human prostate cancer cells DU145. It was found that after the treatment of NCTD with different concentrations (25-100 μM), the cell proliferation was significantly inhibited, which led to the appearance of micronucleus (MN). Moreover, the cells could be killed in a dose-/time-dependent manner along with the reduction of PCNA (proliferating cell nuclear antigen) expression, destruction of mitochondrial membrane potential (MMP), down-regulation of MnSOD, induction of ROS, depletion of ATP, and activation of AMPK (Adenosine 5'-monophosphate -activated protein kinase) . In addition, a remarkable release of cytochrome c was found in the cells exposed to 100 μM NCTD and exogenous SOD-PEG could eliminate the generation of NCTD-induced MN. In conclusion, our studies indicated that NCTD could induce the collapse of MMP and mitochondria dysfunction. Accumulation of intercellular ROS could eventually switch on the apoptotic pathway by causing DNA damage and depleting ATP.

  5. Norcantharidin induced DU145 cell apoptosis through ROS-mediated mitochondrial dysfunction and energy depletion.

    Directory of Open Access Journals (Sweden)

    Bo Shen

    Full Text Available Norcantharidin (NCTD, a demethylated analog of cantharidin derived from blister beetles, has attracted considerable attentions in recent years due to their definitely toxic properties and the noteworthy advantages in stimulating bone marrow and increasing the peripheral leukocytes. Hence, it is worth studying the anti-tumor effect of NCTD on human prostate cancer cells DU145. It was found that after the treatment of NCTD with different concentrations (25-100 μM, the cell proliferation was significantly inhibited, which led to the appearance of micronucleus (MN. Moreover, the cells could be killed in a dose-/time-dependent manner along with the reduction of PCNA (proliferating cell nuclear antigen expression, destruction of mitochondrial membrane potential (MMP, down-regulation of MnSOD, induction of ROS, depletion of ATP, and activation of AMPK (Adenosine 5'-monophosphate -activated protein kinase . In addition, a remarkable release of cytochrome c was found in the cells exposed to 100 μM NCTD and exogenous SOD-PEG could eliminate the generation of NCTD-induced MN. In conclusion, our studies indicated that NCTD could induce the collapse of MMP and mitochondria dysfunction. Accumulation of intercellular ROS could eventually switch on the apoptotic pathway by causing DNA damage and depleting ATP.

  6. Serine/threonine phosphatases in socioeconomically important parasitic nematodes--prospects as novel drug targets?

    Science.gov (United States)

    Campbell, Bronwyn E; Hofmann, Andreas; McCluskey, Adam; Gasser, Robin B

    2011-01-01

    Little is known about the fundamental biology of parasitic nematodes (=roundworms) that cause serious diseases, affecting literally billions of animals and humans worldwide. Unlocking the biology of these neglected pathogens using modern technologies will yield crucial and profound knowledge of their molecular biology, and could lead to new treatment and control strategies. Supported by studies in the free-living nematode, Caenorhabditis elegans, some recent investigations have provided improved insights into selected protein phosphatases (PPs) of economically important parasitic nematodes (Strongylida). In the present article, we review this progress and assess the potential of serine/threonine phosphatase (STP) genes and/or their products as targets for new nematocidal drugs. Current information indicates that some small molecules, known to specifically inhibit PPs, might be developed as nematocides. For instance, some cantharidin analogues are known to display exquisite PP-inhibitor activity, which indicates that some of them could be designed and tailored to specifically inhibit selected STPs of nematodes. This information provides prospects for the discovery of an entirely novel class of nematocides, which is of paramount importance, given the serious problems linked to anthelmintic resistance in parasitic nematode populations of livestock, and has the potential to lead to significant biotechnological outcomes.

  7. Induction of mitochondrial alternative oxidase in response to a cell signal pathway down-regulating the cytochrome pathway prevents programmed cell death.

    Science.gov (United States)

    Vanlerberghe, Greg C; Robson, Christine A; Yip, Justine Y H

    2002-08-01

    Treatment of tobacco (Nicotiana tabacum L. cv Petit Havana SR1) cells with cysteine (Cys) triggers a signal pathway culminating in a large loss of mitochondrial cytochrome (cyt) pathway capacity. This down-regulation of the cyt path likely requires events outside the mitochondrion and is effectively blocked by cantharidin or endothall, indicating that protein dephosphorylation is one critical process involved. Generation of reactive oxygen species, cytosolic protein synthesis, and Ca(2+) flux from organelles also appear to be involved. Accompanying the loss of cyt path is a large induction of alternative oxidase (AOX) protein and capacity. Induction of AOX allows the cells to maintain high rates of respiration, indicating that the lesion triggered by Cys is in the cyt path downstream of ubiquinone. Consistent with this, transgenic (AS8) cells unable to induce AOX (due to the presence of an antisense transgene) lose all respiratory capacity upon Cys treatment. This initiates in AS8 a programmed cell death pathway, as evidenced by the accumulation of oligonucleosomal fragments of DNA as the culture dies. Alternatively, wild-type cells remain viable and eventually recover their cyt path. Induction of AOX in response to a chemical inhibition of the cyt path (by antimycin A) is also dependent upon protein dephosphorylation and the generation of reactive oxygen species. Common events required for both down-regulation of the cyt path and induction of AOX may represent a mechanism to coordinate the biogenesis of these two electron transport paths. Such coordinate regulation may be necessary, not only to satisfy metabolic demands, but also to modulate the initiation of a programmed cell death pathway responsive to mitochondrial respiratory status.

  8. Structural Basis for the Catalytic Activity of Human Serine/Threonine Protein Phosphatase type 5 (PP5)

    Science.gov (United States)

    Swingle, Mark R.; Ciszak, Ewa M.; Honkanen, Richard E.

    2004-01-01

    Serine/threonine protein phosphatase-5 (PP5) is a member of the PPP-gene family of protein phosphatases that is widely expressed in mammalian tissues and is highly conserved among eukaryotes. PP5 associates with several proteins that affect signal transduction networks, including the glucocorticoid receptor (GR)-heat shock protein-90 (Hsp90)-heterocomplex, the CDC16 and CDC27 subunits of the anaphase-promoting complex, elF2alpha kinase, the A subunit of PP2A, the G12-alpha / G13-alpha subunits of heterotrimeric G proteins and DNA-PK. The catalytic domain of PP5 (PP5c) shares 35-45% sequence identity with the catalytic domains of other PPP-phosphatases, including protein phosphatase-1 (PP1), -2A (PP2A), -2B / calcineurin (PP2B), -4 (PP4), -6 (PP6), and -7 (PP7). Like PP1, PP2A and PP4, PP5 is also sensitive to inhibition by okadaic acid, microcystin, cantharidin, tautomycin, and calyculin A. Here we report the crystal structure of the PP5 catalytic domain (PP5c) at a resolution of 1.6 angstroms. From this structure we propose a mechanism for PP5-mediated hydrolysis of phosphoprotein substrates, which requires the precise positioning of two metal ions within a conserved Asp(sup 271)-M(sub 1):M(sub 2)-W(sup 1)-His(sup 304)-Asp(sup 274) catalytic motif. The structure of PP5c provides a possible structural basis for explaining the exceptional catalytic proficiency of protein phosphatases, which are among the most powerful known catalysts. Resolution of the entire C-terminus revealed a novel subdomain, and the structure of the PP5c should also aid development of type-specific inhibitors.

  9. Characterisation of leukocytes in a human skin blister model of acute inflammation and resolution.

    Science.gov (United States)

    Jenner, William; Motwani, Madhur; Veighey, Kristin; Newson, Justine; Audzevich, Tatsiana; Nicolaou, Anna; Murphy, Sharon; Macallister, Raymond; Gilroy, Derek W

    2014-01-01

    There is an increasing need to understand the leukocytes and soluble mediators that drive acute inflammation and bring about its resolution in humans. We therefore carried out an extensive characterisation of the cantharidin skin blister model in healthy male volunteers. A novel fluorescence staining protocol was designed and implemented, which facilitated the identification of cell populations by flow cytometry. We observed that at the onset phase, 24 h after blister formation, the predominant cells were CD16hi/CD66b+ PMNs followed by HLA-DR+/CD14+ monocytes/macrophages, CD11c+ and CD141+ dendritic cells as well as Siglec-8+ eosinophils. CD3+ T cells, CD19+ B cells and CD56+ NK cells were also present, but in comparatively fewer numbers. During resolution, 72 h following blister induction, numbers of PMNs declined whilst the numbers of monocyte/macrophages remain unchanged, though they upregulated expression of CD16 and CD163. In contrast, the overall numbers of dendritic cells and Siglec-8+ eosinophils increased. Post hoc analysis of these data revealed that of the inflammatory cytokines measured, TNF-α but not IL-1β or IL-8 correlated with increased PMN numbers at the onset. Volunteers with the greatest PMN infiltration at onset displayed the fastest clearance rates for these cells at resolution. Collectively, these data provide insight into the cells that occupy acute resolving blister in humans, the soluble mediators that may control their influx as well as the phenotype of mononuclear phagocytes that predominate the resolution phase. Further use of this model will improve our understanding of the evolution and resolution of inflammation in humans, how defects in these over-lapping pathways may contribute to the variability in disease longevity/chronicity, and lends itself to the screen of putative anti-inflammatory or pro-resolution therapies.

  10. 艾易舒联合FOLFIRI方案治疗复发性胃癌的临床研究%Clinical Study of Ai Yishu Combined with FOLFIRI Regimen in the Treatment of Recurrent Gastric Cancer

    Institute of Scientific and Technical Information of China (English)

    武振明; 刘琪; 史素梅; 于士玉

    2013-01-01

    Objective Observation of disodium cantharidinate and vitamin B6 injection (AI Yi Shu) on the synergetic ef ect of recurrent gastric cancer patients with chemotherapy. Methods 64 patients were randomly divided into two groups,the treatment group of 32 cases,the application of Ai Yishu combined with chemotherapy;32 cases in the control group chemotherapy alone,compared with two groups of antitumor ef icacy,myelosuppression and gastrointestinal tract reaction. Results The treatment group of 32 cases,antitumor ef iciency is 40.63%,control group 32 cases,antitumor ef iciency is 43.75%,and there is no significant dif erence between the two groups (P>0.05);treatment group Ⅲ,Ⅳ myelosuppression and digestive tract reaction rates were:46.9%,40.6%,group Ⅲ,Ⅳ myelosuppression and digestive tract reaction rates were:75%,65.6%,there was significant dif erence between the two groups (P0.05);治疗组Ⅲ、Ⅳ骨髓抑制和消化道反应发生率分别为:46.9%、40.6%,对照组Ⅲ、Ⅳ骨髓抑制和消化道反应发生率分别为:75.0%、65.6%,两组比较有显著性差异(P<0.05)。结论斑蝥酸钠维生素B6注射液改善患者症状、减少化疗毒副反应的作用,长期应用可能会提高化疗疗效。

  11. Application of biological pesticides in the control of codling moth, Cydia pomonella (L.)%生物源农药在苹果蠹蛾防治中的应用

    Institute of Scientific and Technical Information of China (English)

    吴正伟; 杨雪清; 张雅林

    2015-01-01

    The codling moth, Cydia pomonella (L.) (Lepidoptera:Tortricidae), a notorious quarantine fruit pest worldwide, poses a serious threat to the main apple producing areas in China. In terms of food safety, environmentally friendly biological pesticides are desirable substitutes for chemical pesticides;the long ̄term use of the latter have caused resistance, preventing its long team use for codling moth control. The present review summarized the use of biological pesticides, including parasitoids, sterilized insect, granu ̄lovirus, entomopathogenic nematodes, Bacillus thuringiensis, entomopathogenic fungi, microsporidia, sex pheromone, cantharidin, and spinosad that have been either applied or suggested to control codling moth. The challenges faced by biological pesticides are al ̄so discussed, and anyhow it will play an important role in the integrated pest management of codling moth due to its characteristics of infinite variety, wide source, good selectivity in application.%苹果蠹蛾是世界性检疫害虫,对我国苹果优势产区构成了巨大威胁。长期依赖化学防治使该虫抗性问题变得十分严峻。为了保障食品安全,以环境友好的生物源农药替代化学农药已成为当前苹果蠹蛾防治的热点。本文对国内外现有的生物源农药,如寄生蜂、不育昆虫、颗粒体病毒、病原线虫、Bt、病原真菌、微孢子虫、性信息素、斑蝥素、多杀菌素等,在苹果蠹蛾防治中的最新应用及其存在的问题进行论述,讨论了生物源农药凭借其种类多、来源广且在用药时期上选择性强等特点,在该虫综合治理中的重要地位及面临的挑战。

  12. Analysis of the adverse drug reaction of the Chinese herbal%活血化瘀中药的不良反应分析

    Institute of Scientific and Technical Information of China (English)

    白宇明; 魏国义

    2013-01-01

    目的 分析活血化瘀中药的不良反应发生情况,促进临床合理用药.方法 通过以中药“不良反应”为关键词,检索CHKD期刊全文数据中1998-2011年国内所有文献,查阅中药致不良反应文献的原文,并进行分析.结果 15种常用活血化瘀基本中药引起的12类不良反应及药源性疾病共计203例,其中累及系统主要为泌尿系统62例,呼吸系统47例,皮肤症状27例,急性中毒13例和循环系统12例.引起不良反应较多的药物为斑蝥(6种)、水蛭、丹参、马钱子(各5种),当归、川芎、乳香、三七(各3种).年龄越大,活血化瘀中草药不良反应构成比越高.女性活血化瘀中草药不良反应构成比较男性高.结论 活血化瘀中药不良反应分类繁多,临床表现多种多样,应引起医务人员和广大患者的重视.%Objective To analyze the adverse drug reaction of blood-activating and stasis-resoloing Chinese herbal medicine.And in order to promote the clinical reasonable using medicine.Methods "Adverse drug reaction" was as the key words,all literature of full text data the CHKD journal from 1998 to 2011 were retrieved,literature of adverse reactions caused by the original inspection Chinese medicine were checked.Results A total of 15 kinds of commonly used blood circulation Chinese medicine caused 12 adverse reactions and drug-induced disease was 203 cases,involving 62 cases of the urinary system,47 cases of the respiratory system,27 cases of skin symptoms,13 cases of acute poisoning and cyclesystem in 12 cases.Drugs to cause adverse reactions were cantharidin (6 species),leeches,Salvia,horse vomica (5),Angelica,Chuanxiong,frankincense,Panax (3).The older,the higher the ratio of adverse reactions of Chinese herbal medicine.The female had higher incidence than men.Conclusion Traditional Chinese medicine has adverse classification and diverse clinical manifestations.The medical staff and the majority of patients should pay more attention on