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国外市场上的降胆固醇新产品
谷华
【期刊名称】《中外食品工业信息》
【年(卷),期】2001(000)006
【摘要】2000年10月,美国(ForbesMedi-Tech)工艺公司分别在澳大利亚和美国市场推出一种有降低胆固醇值效果的新产品Pytrol“植物性固醇”——非酯化的妥尔油(木桨、浮油)植物固醇。
1999年,分别对32名高胆固醇的男性患者每天给予预先加温的人造黄油,它是含1.7克植物性固醇的纯妥尔油的特制人造黄油。
30天以后发现,受试高胆固醇者的低密度脂蛋白胆固醇值降低约15％。
该公司生产的植物性固醇(商品名“Reducd”)被添加剂利用在脂肪以外的各种不同食品中。
【总页数】1页(P51)
【作者】谷华
【作者单位】无
【正文语种】中文
【中图分类】TS202.3
【相关文献】
1.降胆固醇乳酸菌的体外筛选及其降胆固醇机理探讨 [J], 黄燕燕;郭均;黎恒希;杨爱君;冯立科;彭小霞;刘冬梅
2.发酵酸肉中降胆固醇乳酸菌的筛选、鉴定及降胆固醇作用 [J], 丁苗;刘洋;葛平珍;王丹;周才琼
3.降胆固醇乳酸菌的筛选及其降胆固醇活性研究 [J], 潘道东;张德珍
4.自然发酵豆酱中降胆固醇乳酸菌的筛选鉴定及对大鼠血清胆固醇的影响 [J], 郭晶晶;张鹏飞;曹承旭;邹婷婷;乌日娜
5.具有降胆固醇功能益生菌的筛选及其体外降胆固醇机制初探 [J], 李雅迪;柳陈坚;龚福明;李晓然
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药品名alcloxaaluminum chlorohydrex aluminum hydroxide benzocainebenzoic acidbenzoyl peroxideboric acidcalcium polysuldfidecalcium thiosulfatecamphorchlorhydroxyquinoline (cloxyquin) chloroxylenolcloxyquin (chlorhydroxyquinoline) coal tardibenzothiopheneestronemagnesium aluminum silicate magnesium sulfatephenolphenolate sodiumphenyl salicylatepovidone-iodinepyrilamine maleateresorcinolresorcinol (as single ingredient only)resorcinol (when combined with sulfur)resorcinol monoacetate (as single ingredient only) resorcinol monoacetate (when combined with sulfur) salicylic acidsalicylic acid (over 2 up to 5%)sodium boratesodium thiosulfatesulfursulfur (when combined w/ resorcinol, resocinol monoacetate) tetracaine hydrochloridethymolvitamin Ezinc oxidezinc stearatezinc sulfidecharcoal, activatedisopropyl alcoholcamphorjuniper tarmentholdiperodonphenacaine hydrochloride atropinebelladonna extractboric acidboroglycerinhydrastisphenolresorcinolsodium salicylic acid phenolate calaminetannic acidwitch hazel (haramelis water) zinc oxidecamphorhydrastismentholturpentine oil (rectified) alcloxaprecipitated sulfur resorcinolsublimed sulfur benzocainebenzyl alcohol dibucainedibucaine hydrochloride dyclonine hydrochloride lidocainepramoxine hydrochloride tetracainetetracaine hydrochloride lidocainepramoxine hydrochloride tetracainetetracaine hydrochloride collinsonia extract Escherichia coli vaccine lappa extract leptandra extractlive yeast cell derivativemulleinaluminum hydroxide gel bismuth oxidebismuth subcarbonatebismuth subgallatebismuth subnitratecalamine (in combination only) cocoa buttercod liver oil (in combination only) glycerinhard fatkaolinlanolinlanolin alcoholsmineral oilpetrolatumshark liver oil (combination only) topical starchwhite petrolatumzinc oxide (combination only)ephedrine sulfateepinephrineepinephrine hydrochlorideepinephrine undecylenatephenylephrine hydrochloridecholecalciferol (vitamin D)cod liver oillive yeast cell derivativePeruvian balsamshark liver oilvitamin Ahydrocortisone (combination)pramoxine hydrochloride (combination)aluminum carbonate gel (basic)aluminum hydroxidealuminum hydroxide-hexitol, stabilized polymer aluminum hydroxide-magnesium carbonate, co-dried gel aluminum hydroxide-magnesium trisilicate, co-dried gel aluminum hydroxide-sucrose powder hydrated aluminum phosphatealuminum phosphate gel (in combination only) bicarbonatebismuth aluminatebismuth carbonatebismuth subcarbonatebismuth subgallatebismuth subnitratecalcium (mono or dibasic salt)calcium carbonatecalcium phosphateCharcoal, activatedcitrate (containing active ingredients: citrate ion, as citric acid or salt) dihydroxyaluminum aminoacetatedihydroxyaluminum aminoacetic aciddihydroxyaluminum sodium carbonateglycine (aminoacetic acid)hydrate magnesium aluminate activated sulfatemagaldratemagnesium aluminosilicatemagnesium aluminosilicatemagnesium carbonatemagnesium glycinatemagnesium hydroxidemagnesium oxidemagnesium trisilicatemagnesium trisilicatemilk solids, driedpotassium bicarbonatepotassium carbonatesodium bicarbonatesodium carbonatesodium potassium tartratesodium potassium tartratetartrate (acid or salt)tricalcium phosphategentian voiletpiperazine citratepyrantel pamoatesodium fluoride gel or pastesodium fluoride powdersodium monolfuorophosphate (gel or paste) sodium monolfuorophosphate (gel or paste) stannous fluoridestannous fluorideacidulated phosphate fluorideacidulated phosphate fluoridecalcium sucrose phosphatedicalcium phosphate dihydratedisodium hydrogen phosphatehydrogen fluoridephosphoric acidsodium bicarbonatesodium carbonatesodium dihydrogen phosphatesodium dihydrogen phosphate monohydratesodium fluoride (aqueous)sodium fluoride (aqueous) (acidulated phosphate fluoride with .01% fl sodium fluoride (aqueous) (acidulated phosphate fluoride with .01% fl sodium monofluorophosphatesodium monofluorophosphate (rinse)sodium phosphatesodium phosphatestannous fluoride (gel)stannous fluoride (rinse)attapulgite, activatedbismuth subnitratecalcium hydroxidecalcium polycarbophil charcoal (activated)pectinpolycarbophilpotassium carbonaterhubarb fluidextractalumina powder, hydrated aluminum hydroxide atropine sulfatebismuth subsalicylate calcium carbonate precipitated carboxymethylcellulose sodium glycinehomatropine methylbromide hyocyamine sulfatekaolinLactobacillus acidophilisLactobacillus bulgaricus Opium powderOpium tinctureparegoricphenyl salicylate (salo) scopolamine hydrobromide sodium carboxymethylcellulose zinc phenolsulfonate aminoacetic acidbismuth subsalicylate cyclizine hydrochloride dimenhydrinate diphenhydramine hydrochloride meclizine hydrochloride phenyl salicylate phosphorated carbohydrate soopolamine hydrobromide zinc phenolsulfonate simethiconealcloxaalum, potassiumaluminum sulfate amyltricresols, secondary basic fuchsin benzethonium chloridebenzoic acidbenzoxiquineboric acidcalcium undecylenatecamphorcamphorated metacresol candicidinchlorothymolchloroxylenolclioquinolclioquinol (lodochlorhydroxyquin) clotrimazolecoal tarcopper undecylenate dichlorophenhaloproginm-cresolmentholmethylparabenmiconazole nitratenystatinoxyquinoline oxyquinoline sulfate phenolphenolate sodium phenyl salicylate povidone-iodine propionic acid propylparaben resorcinol salicylic acid sodium borate sodium caprylate sodium propionate sulfurtannic acidthymoltolindate tolnaftate triacetin undecylenic acid zinc caprylatezinc propionatezinc undecylenatequininemercury-containing ingredientpara-chloromercuriphenolammoniated mercurycalomel (mercurous chloride)merbromin (mercurochrome)mercufenol chloride (orthochloromercuriphenol, orthohydroxyphenyl mercuric chloride (bichloride of mercury, mercury chloride) mercuric oxide, yellowmercuric salicylatemercuric sulfide, redmercurymercury oleatemercury sulfidenitromersolpara-chloromercuriphenolphenylmercuric nitratethimerosalvitromersolzyloxinbenzalkonium chloride benzalkonium chloride benzalkonium chloride benzalkonium chloride benzalkonium chloride benzalkonium chloride benzalkonium chloride benzalkonium chloride benzalkonium chloride benzalkonium chloride benzalkonium chloride benzalkonium chloride benzalkonium chloride benzalkonium chloride benzalkonium chloride bismuth subsalicylate calcium undecylenate chloroxlyneol chloroxlyneol chloroxlyneol chloroxlyneol chloroxlyneolchloroxlyneolchloroxlyneolchloroxlyneolchloroxlyneolcloflucarbanfluorosalanhexachlorophenehexylresorcinolhexylresorcinolhexylresorcinolhexylresorcinolhexylresorcinolhexylresorcinolhexylresorcinolhexylresorcinolhydrogen peroxideiodine complex/phosphate ester of alkylaryloxy polyethylene iodine complex/phosphate ester of alkylaryloxy polyethylene iodine complex/phosphate ester of alkylaryloxy polyethylene iodine complex/phosphate ester of alkylaryloxy polyethylene iodine complex/phosphate ester of alkylaryloxy polyethyleneiodine complex/phosphate ester of alkylaryloxy polyethylene iodine complex/phosphate ester of alkylaryloxy polyethylene iodine tinctureiodine tinctureiodine tinctureiodine tinctureiodine tinctureiodine tinctureiodine tinctureiodine tinctureiodine topical solutionmethylbenzethonium chloridemethylbenzethonium chloridemethylbenzethonium chloridemethylbenzethonium chloridemethylbenzethonium chloridemethylbenzethonium chloridemethylbenzethonium chloridenonylphenoxypoly (ethyleneoxy) ethanol iodine nonylphenoxypoly (ethyleneoxy) ethanol iodine nonylphenoxypoly (ethyleneoxy) ethanol iodine nonylphenoxypoly (ethyleneoxy) ethanol iodinenonylphenoxypoly (ethyleneoxy) ethanol iodine nonylphenoxypoly (ethyleneoxy) ethanol iodineoxyquinolinephenolphenolphenolphenolphenolphenolphenolphenolphenolphenolphenolphenolphenolphenolphenolpoloxamer 188poloxamer-iodine complexpoloxamer-iodine complexpoloxamer-iodine complex poloxamer-iodine complex poloxamer-iodine complex poloxamer-iodine complex poloxamer-iodine complex povidone-iodine povidone-iodine povidone-iodine povidone-iodine povidone-iodine povidone-iodine povidone-iodine povidone-iodine povidone-iodine resorcinolshark liver oilsodium propionate triclocarban triclocarban triclocarban triclocarban triclocarbantriclocarbantriclocarbantriclocarbantriclosantriclosantriclosantriclosantriclosantriclosantriclosantriclosantriple dyetriple dyetriple dyetriple dyetriple dyetriple dyetriple dyetriple dyeundecoylium chlorideiodine complex undecoylium chlorideiodine complexundecoylium chlorideiodine complexundecoylium chlorideiodine complexundecoylium chlorideiodine complexundecoylium chlorideiodine complexundecoylium chlorideiodine complexaluminum sulfate buffered w/ sodium aluminum lactate alum, potassiumaluminum bromohydratealuminum chloride (alcoholic solutions)aluminum chloride (aqueous solution) (aerosol only) aluminum chloride (nonaerosol aqueous solution) aluminum chlorohydratealuminum chlorohydrex polyethylene glycol aluminum chlorohydrex propylene glycolaluminum dichlorohydratealuminum dichlorohydrex polyethylene glycol aluminum dichlorohydrex propylene glycol aluminum sesquichlorohydratealuminum sesquichlorohydrate poylethylene glycolaluminum sesquichlorohydrate propylene glycol aluminum sulfatealuminum sulfate, buffered (aerosol only) aluminum zirconium octachlorohydrate aluminum zirconium octachlorohydrex gly aluminum zirconium pentachlorohydrate aluminum zirconium pentachlorohydrex gly aluminum zirconium tetrachlorohydrate aluminum zirconium tetrachlorohydrex gly aluminum zirconium trichlorohydrate aluminum zirconium trichlorohydrex gly sodium aluminum chlorohydroxy lactate aminacrine hydrochloridecorn oil, aqueous emulsionsoybean oil, hydrogenated (powder) salicylic acidsalicylic acidacetic acid, glacialallantoin (5-ureidohydantoin)ascorbic acidbelladonna alkaloidschlorobutanoldiperodon hydrochlorideichthammoliodinemethyl salicylate methylbenzethonium chloride panthenolphenoxyacetic acidphenyl salicyiatevitamin Azinc chlorideatropa belladonnaatropine sulfatebelladonna alkaloidsdatura stramonium brompheniramine maleate chlorcyclizine hydrochloride chlorpheniramine maleate dexbromopheniramine maleate dexchlorpheniramine maleatediphenhydramine citrate diphenhydramine hydrochloride doxylamine succinate menthol (mouthwash)metaproterenol sulfate methapyrilene fumarate methapyrilene hydrochloride peppermint oil (mouthwash) phenindamine tartrate pheniramine maleate phenyltoloxamine dihydrogen citrate phenyltoloxamine hydrochloride pyrilamine maleate thenyldiamine hydrochloride thonzylamine hydrochloride triprolidine hydrochloride benzonatatecamphorcamphorcaramiphen edisylate carbetapentane citrate chlophedianol hydrochloridecod liver oilcodeinecodeine phosphatecodeine sulfatecreosote, beechwood dextromethorphan dextromethorphan hydrobromide diphenhydramine citrate diphenhydramine hydrochloride elm barkethylmorphine hydrochloride eucalyptoleucalyptoleucalyptus oileucalyptus oileucalyptus oilhorehoundhydrocodone bitartrate mentholmentholmentholmentholnoscapinenoscapine hydrochloride peppermint oilturpentine oil (oral)turpentine oil (topical/inhalant) aminophyllinebelladonna alkaloids ephedrineephedrine hydrochloride ephedrine sulfateepinephrineepinephrineepinephrine bitartrate epinephrine bitartrate epinephrine hydrochloride euphorbia pilulifera methoxyphenamine hydrochloride pseudoephedrine hydrochloride pseudoephedrine sulfate racephedrine hydrochloride racepinephrine hydrochloride racepinephrine hydrochloride theophylline (in combination) theophylline calcium salicylate theophylline sodium glycinatetheophylline, anhydrousammonium chlorideantimony potassium tartratebeachwood creosotebenzoin preparations (compound tincture of benzoin, tincture of benz camphorchloroformeucalyptol/eucalyptus oilguaifenesinhorehoundiodides (calcium iodide anyhydrous, hydroidic acid syrup, iodized lim ipecacipecac fluidextractipecac syrupmenthol/peppermint oilpine tar preparationspotassium guaiacolsulfonatesodium citratesquill preparations (squill, squill extract)terpin hydrate prearations (terpin hydrate, terpin hydrate elixer)tolu preparations (tolu, tolu balsalm, tolu balsalm tincture)turpentine oil (spirits of turpentine) caffeinephenobarbitalallyl isothiocyanatebornyl acetate (topical) camphorcamphor (lozenge)cedar leaf oil (topical) creosote, beechwood (oral) creosote, beechwood (topical) ephedrine (aqueous)ephedrine (jelly)ephedrine (oral)ephedrine hydrochloride (aqueous) ephedrine hydrochloride (jelly) ephedrine hydrochloride (oral) ephedrine sulfate (aqueous) ephedrine sulfate (jelly) ephedrine sulfate (oral) eucalyptol (lozenge)eucalyptol (mouthwash) eucalyptus oileucalyptus oil (lozenge)eucalyptus oil (mouthwash) levmetamfetaminelevmetamfetaminementholmustard oil (alltlishthiocyanate) (tpoical/inhalant) naphazoline hydrochloridenaphazoline hydrochloridenaphazoline hydrochloride (jelly)naphazoline hydrochloride (jelly) oxymetazoline hydrochloride (aqueous)oxymetazoline hydrochloride (aqueous) oxymetazoline hydrochloride (jelly) peppermint oilpeppermint oilpeppermint oilphenylephrine bitartrate (effervescent) phenylephrine hydrochloridephenylephrine hydrochloride (aqueous) phenylephrine hydrochloride (aqueous) phenylephrine hydrochloride (aqueous)phenylephrine hydrochloride (aqueous) phenylephrine hydrochloride (jelly) phenylephrine hydrochloride (jelly) phenylephrine hydrochloride (jelly) phenylpropanolamine bitartrate phenylpropanolamine hydrochloride (oral) phenylpropanolamine hydrochloride (topical) phenylpropanolamine maleate propylhexedrinepseudoephedrine hydrochloride pseudoephedrine sulfate pseudoephedrine sulfate (oral) racephedrine hydrochloride (oral/topical) thenyldiamine hydrochloride thenyldiamine hydrochloridethymolthymol (lozenge)thymol (mouthwash)turpentine oil (spirits of turpentine) (oral) turpentine oil (spirits of turpentine) (topical) xylometazoline hydrochloride (aqueous) xylometazoline hydrochloride (aqueous)xylometazoline hydrochloride (jelly) xylometazoline hydrochloride (jelly) salicylic acidselenium sulfideselenium sulfide, micronized sulfurpyrithione zincpyrithione zinccoal tarsalicylic acidcoal tarsalicylic acidselenium sulfidepyrithione zincpyrithione zincalkyl isoquinolinium bromide allantoinbenzalkonium chloride benzalkonium chloride benzocaineboric acidcalcium undecylenate captanchloroxylenolcoal tarcolloidal oatmealcresol, saponated ethohexadioleucalyptol hydrocortisone preparations juniper tarlauryl isoquinolinium bromide mentholmercury oleatemethyl salicylate methylbenzethonium chloride phenolphenolate sodiumpine tarpovidone-iodineresorcinolsodium boratesodium salicylatethymolundecylenic acidsodium bromidebismuth subgallatecharcoal, activatedchlorophyllin copper complex almadrate sulfatealuminum hydroxidecalcium carbonate dihydroxyaluminum sodium carbonate magnesium hydroxidemagnesium trisilicatesodium bicarbonatesodium citratesimethiconepancreatinpancrelipaseglutamic acid hydrochloridealcoholamylaseanise seedaromatic powderasafetidaaspergillus oryza enzymes bacillus acidophilusbeanbelladonna alkaloidsbelladonna leaves, powdered exrtact betaine hydrochloridebismuth sodium tartratebismuth subcarbonatebismuth subgallateblack radish powderblessed thistle (cnicus benedictus) buckthorncalcium gluconatecapsicumcapsicum, fluid extract of carbon carboncascara sagrada extract catechu, tincturescatnipcellulasechamomile flowers charcoal, wood/activated chloroformcinnamon oilcinnamon tincturecitrus pectin dehyrocholic acid diastasediastase maltdog grassduodenal substance elecampaneetherfennel acidgalegagarlic, dehydratedgingerglycinehectoritehemicellulase homatropine methylbromidehorsetailhuckleberryhydrastis canadensis (golden seal) hydrastis fluid extract hydrochloric acidiodineiron ox bilejohnswortjuniper tarkaolin, colloidalknotgrasslactic acidlactoselavender compound, tincture of lindenlipaselysine hydrochloridemannitolmycozymemyrrh, fluid extract ofnettlenickel-pectinnux vomica extract orthophosphoric acid ox bile extractpapainpectinpeppermint peppermint oil peppermint spirit pepsinphenacetin potassium bicarbonate potassium carbonate prolaseproteaserhubarb fluid extract sennasodium chloride sodium salicylate sorbitolstem bromelain strawberrystrychninetannic acidtrilliumwoodruffipecac syrupaspirinbenzyl alcoholcamphorated metacresolchloral hydratechlorobutanolcyclomethycaine sulfateeugenolhexylresorcinolmethapyrilene hydrochloridesalicylamidetetracainethymolchloral hydrateeucalyptus oilallyl isothiocyanateallyl isothiocyanateammonia solution, strong (ammonia water, strong)aspirinbismuth sodium tartrate camphor (exceding 3 percent) capsaicincapsicumcapsicum oleoresinchloral hydrate chlorobutanol cyclomethycaine sulfate eucalyptus oileugenolglycol salicylatehistamine dihydrochloride menthol exceeding 1% methapyrilene hydrochloride methyl nicotinatemethyl salicylatepectinsalicylamidetannic acidthymoltripelennamine hydrochloridetrolamine salicylate (triethanolamine salicylate) turpentine oilzinc sulfatealcoholalcohol, ethoxylated alkylbenzalkonium chloridecalamineergot fluidextractferric chloridepanthenolpeppermint oilpyrilamine maleatesodium boratetrolamine salicylate (trietnanolamine salicylate) turpentine oilzinc oxidezirconium oxidebenzocainebenzyl alcoholcamphorated metacresolephedrine hydrochloride lidocainealcoholaspirin benzethonium chloride benzocaine (0.5 - 1.25%) bithionolcalaminecetalkonium chloride chloral hydrate chlorobutanol chlorpheniramine maleate creosote, beechwood cyclomethycaine sulfate dexpanthenol diperodon hydrochloride eucalyptus oileugenolglyceringlycol salicylate hectorite hexylresorcinolhydrogen peroxideimpatiens biflora tinctureiron oxideisopropyl alcohollanolinlead acetatemerbrominmercuric chloridemethapyrilene hydrochloridepanthenolparethoxycaine hydrochloride phenyltoloxamine dihydrogen citrate povidone-vinylacetate copolymers pyrilamine maleatesalicylamidesalicylic acidsimethiconesulfurtannic acidthymoltrolamine salicylate (trietnanolamine salicylate)turpentine oilzirconium oxidezyloxinallantoinaluminum acetatealuminum chloride hexahydrate benzocainebutamben picratecamphorcamphorcupric sulfate dexpanthenoldibucainedibucaine hydrochloride dimethisoquin hydrochloride diphenhydramine hydrochloride dyclonine hydrochloride hydrocortisone hydrocortisone (0.25-5%) hydrocortisone (0.5-1%) hydrocortisone acetate hydrocortisone acetatehydrocortisone acetate (0.25-5.0%) hydrocortisone acetate (0.25%-0.5%) juniper tarlidocainelidocaine hydrochloridementholmenthol (0.1 to 1.0%)obtundia surgical dressingphenolphenolate sodiumpramoxine hydrochloride resorcinolsodium bicarbonatetetracaine hydrochloridetopical starchtripelennamine hydrochloride trolaminezinc acetatezinc oxidebacitracinbacitracin zincchlortetracycline hydrochlorideneomycin sulfateoxytetracycline hydrochloride (combination only)polymyxin b sulfate (combination only)tetracycline hydrochloridegramicidinneomycin ointment (combination only)neomycin sulfate creamalkyl dimethyl amine oxide and alkyl dimethyl glycinealoe vera [see aloe]dicalcium phosphate dihydrate [see calcium phosphate, dibasic] hydrogen peroxide and povidone iodinehydrogen peroxide and sodium bicarbonatehydrogen peroxide, sodium citrate, sodium lauryl sulfate, peppermint oil and sage oilpolydimethylsiloxane and poloxamersanguinaria extractsodium bicarbonatestannous pyrophosphate and zinc citratezinc citratesodium sulfide (aqueous)aspirinaspirin (buffered) aspirinaspirin (buffered) acetaminophen acetanilide aminobenzoic acid antipyrineany atropine ingredient any ephedrine ingredient aspirin, aluminum aspirin, calcium aspirin, calcium caffeinecalcium salicylate carbaspirin calcium choline salicylate codeinecodeine phosphate codeine sulfate ibuprofenibuprofeniodoantipyrine (idopyrine)lysine aspirinmagnesium salicylate methapyrilene fumarate phenacetinpheniramine maleate phenyltoloxamine citrate phenyltoloxamine dihydrogen citrate potassium salicylatepyrilamine maleatequininesalicylamidesalsalatesodium para-aminobenzoate sodium salicylateagaralpha cellulosecalcium polycarbophil carrageenan (degraded) carrageenan (native)guar gumplantago ovata husksplantago seedpsylllium (hemicellulose)sodium carboxymethylcelluloseglycerinsorbitolmineral oilmagnesium citrate (oral)magnesium hydroxidemagnesium sulfatesodium phosphate, dibasicsodium phosphate, monobasictartaric acidaloe ingredients (aloe, aloe extract, aloe flower extract) aloinbile salts/acidscalcium pantothenatecalomelcasanthranolcascara fluidextract aromaticcascara sagrada barkcascara sagrada extractcascara sagrada fluidextract castor oilcolocynthdanthronelaterin resinfrangulagambogeipomeajalapox bilephenolphthaleinpodophyllum resin (podophyllin) prune concentrate dehydrate prune powderrhubarb, Chinesesodium oleatedocusate calcium sulfosuccinate docusate potassium sulfosuccinate docusate sodium sulfosuccinate poloxamerbisacodylbrancarbon dioxide, released carboxymethylcellulose sodiumkaraya gummalt soup extractmethylcelluloseplantago seed husks [see psyllium seed husks ] plantago seed, blond [see plantago seed] polycarbophilpsyllium (hemicellulose) [see plantago seed]psyllium hydrophilic mucilloidpsyllium seedpsyllium seed (blond)psyllium seed huskssenna fluidextractsenna pod concentratesenna syrupsennosides a and bacetaminophenaspirincaffeinecarbaspirin calcium。
仿制降胆固醇药物立普妥项目
世界上最畅销的用于降低胆固醇的药物, 美国辉瑞药业公司研制生产的立普妥（Lipitor）的专利保护期已于2011年11月30正式到期, 这意味着通用版本的立普妥的生产和销售成为可能，就是说立普妥药物可以使用它的化学名称，也就是它的通用名阿托伐他汀（Atorvastatin），不受限制地由非专利药公司生产和销售。
在过去的20年中，立普妥每年大约为辉瑞公司带来130亿美元的销售额。
印度的兰伯西公司首先获得批准，在新泽西州新布伦斯维克欧姆实验室开始仿制生产10毫克钙片剂(mg), 20毫克, 40毫克和80毫克的阿托伐他汀。
美国辉瑞公司也与以新泽西为基地的华生公司（Watson Pharmaceuticals）合作继续生产通用版本的立普妥-阿托伐他汀，并已于2011年11月30日开始销售通用版本的立普妥。
华生公司首席执行官保罗沃森说, 该公司将作为一个品牌药物以50%的折扣价格出售通用版本的立普妥。
据《华尔街日报》分析, 最近的价格范围从列表立普妥$ 3.50到$ 5每药丸, 这取决于它所在的国家。
服用通用版本的立普妥的患者可以节省很多钱。
Effects of in-vivo and in-vitro environments on the metabolism of the cumulus±oocyte complex and itsin¯uence on oocyte developmental capacityM.L.Sutton,R.B.Gilchrist and J.G.Thompson1Reproductive Medicine Unit,Department of Obstetrics and Gynaecology,University of Adelaide,The Queen Elizabeth Hospital, Woodville Road,Woodville,SA,5011,Australia1To whom correspondence should be addressed at:E-mail:jeremy.thompson@.auThere has been an improvement in the blastocyst rates achieved following in-vitro embryo production that can largely be attributed to improved embryo culture conditions based on an increased knowledge of the in-vivo environment,as well as the metabolic needs of the embryo.Despite this,in-vitro oocyte maturation(IVM)conditions have remained largely unchanged.Within the antral follicle,numerous events affect oocyte maturation and the acquisition of developmental competency,including:interactions between somatic cells of the follicle(in particular cumulus cells)and the oocyte;the composition of follicular¯uid;and the temperature and vascularity of the follicular environment.Many of these factors change with follicle size and oocyte growth.In contrast,culture conditions for IVM are based on somatic cells that often do not re¯ect the follicular environment,and/or have complex compositions or additives such as macromolecule supplements that are unde®ned in nature.Metabolites included in media such as glucose,pyruvate,oxygen and amino acids have been shown to have differential in¯uences on oocyte maturation and competency.Manipulation of these factors and application of gained knowledge of the in-vivo environment may result in improved in-vitro oocyte maturation and overall in-vitro embryo production. Key words:culture conditions/follicular¯uid/in-vitro maturation/metabolism/oocyte maturationIntroductionOocyte maturation is the culmination of a prolonged period of oocyte growth and development within the growing follicle,and the short interval of meiotic maturation at ovulation.It is over the long phase of weeks to months that the oocyte,in a highly co-ordinated manner,gradually acquires the cellular machinery required to support early embryonic development.This capacity of the oocyte to sustain early development,called oocyte developmental competence,is intrinsically linked to the process of folliculogenesis and to the health of the developing follicle. The follicular environment also maintains oocytes in an arrested state of meiosis,at the diplotene stage of prophase I[also called the germinal vesicle(GV)stage].The last phase of oocyte maturation,meiotic maturation of the immature GV oocyte, germinal vesicle breakdown(GVBD)and progression to meta-phase II(MII),is induced in vivo by the pre-ovulatory gonadotrophic surge.Alternatively,arti®cial release of the oocyte from the inhibitory environment of the follicle leads to spontaneous meiotic maturation in vitro(Pincus and Enzmann, 1935).Oocyte in-vitro maturation(IVM)is a viable phenomenon as oocytes matured,fertilized and cultured in vitro can generate embryos with full developmental potential after embryo transfer.Meiotic maturation following liberation of the oocyte from the follicle was®rst described during the1930s(Pincus and Enzmann,1935),but it was not until the mid-1960s that the potential for IVM as a step in the process of embryo production was recognized(Edwards,1965).However,the ability of the oocyte to undergo meiotic maturation is a poor marker of oocyte developmental capacity(Moor and Trounson,1977).In most species examined,oocytes matured in vitro are compromised in their developmental capacity compared with oocytes matured in vivo(Bousquet et al.,1999;Farin et al.,2001;Yang et al.,2001; Combelles et al.,2002;Dieleman et al.,2002;Holm et al.,2002). Furthermore,the proportion of pregnancies achieved following IVM of human oocytes from unstimulated patients is minute (Trounson et al.,1994;Cha et al.,2000).With further research, IVM has the potential to become a viable alternative to ovarian stimulation,especially for the treatment of patients with fertility disorders who are at an increased risk of developing ovarian hyperstimulation syndrome when treated with exogenous hor-mones,for example polycystic ovarian syndrome.Our understanding of what constitutes a developmentally competent oocyte recovered from antral follicles remains poor, although it is clear that the quality of the follicular environmentHuman Reproduction Update,Vol.9,No.1pp.35±48,2003DOI:10.1093/humupd/dmg009ÓEuropean Society of Human Reproduction and Embryology35 by guest on July 14, 2011 Downloaded fromfrom which the oocyte originates is a major determining factor.Despite this,little is known about how the nutrient requirements of the cumulus±oocyte complex(COC)impact on subsequent embryo development.For example,the most commonly used oocyte maturation media used today are formulations designed many years ago for culture of non-ovarian somatic cells.There are no studies that directly correlate the metabolic needs of the COC with developmental outcomes. However,the pioneering work of Downs and colleagues has clearly shown that availability of energy substrates can regulate meiotic resumption in oocytes from antral follicles,with small alterations in substrate concentrations either suppressing or inducing meiosis(Downs and Mastropolo,1994;Downs and Hudson,2000).In contrast,the effect of cell±cell signalling between the oocyte and granulosa cells during the earliest stages of folliculogenesis on metabolism of the oocyte is unknown and is likely to remain technically dif®cult to study.In this review,we will examine the composition of the antral follicular environment and how this relates to developmental outcome,and also the metabolism of the oocyte and the surrounding cellular vestment and relate these to developmental outcome and the current development of IVM media.Oocyte±follicular cell interactionsOocyte±follicular cell communication pathwaysThe follicular environment`programmes'oocyte developmental competence.Clearly,oocyte growth and development are absolutely dependent on the nurturing capacity of the follicle,in particular of the granulosa munication between the germ cell and somatic cell compartments of the follicle occurs via paracrine and gap-junctional signalling(Figure1).Indeed,both forms of communication are essential for normal oogenesis and folliculogenesis(Dong et al.,1996;Simon et al.,1997). Traditionally,research has focused on just one direction of this communication axisÐthat is,on granulosa cell support of the developing oocyteÐbut recent studies have demonstrated the importance of a bi-directional communication axis(Albertini et al.,2001).It is now becoming clear that oocyte paracrine signals are pivotal regulators of granulosa cell and ovarian function (Eppig,2001).Two key oocyte molecules identi®ed so far are growth differentiation factor9(GDF-9)and GDF-9B[also called bone morphogenic protein15(BMP-15)].These oocyte growth factors are critical for progression of the very earliest stages of folliculogenesis(Dong et al.,1996;Galloway et al.,2000),and then in late follicular development these oocyte-secreted factors play an important role in the differentiation of different granulosa cell lineages(Eppig et al.,1997;Li et al.,2000)and in the regulation of key granulosa cell functions(Elvin et al.,1999; Joyce et al.,2000;Otsuka et al.,2001).The highly specialized cumulus cells have distinctive trans-zonal cytoplasmic processes(TZP),which penetrate through the zona pellucida and abut the oolemma.Gap junctions at the ends of these TZP(and between cumulus cells)allow the transfer of low molecular-weight molecules between oocyte and cumulus cell, and also between cumulus cells(Eppig,1991).Gap-junctional communication in the follicle is essential for development and fertility.Both folliculogenesis and oogenesis fail in mice homozygous null for either connexin-37(the protein building block of oocyte±cumulus cell gap junctions;Simon et al.,1997), or connexin-43(the protein associated with gap junctions between granulosa cells;Ackert et al.,2001).Glucose metabolites,amino acids and nucleotides are all able to pass between oocyte and cumulus cells.In addition,gap junctions participate in oocyte meiotic regulation by allowing the passage of small regulatory molecules such as cAMP and purines(Dekel and Beers,1980; Salustri and Siracusa,1983;Eppig and Downs,1984;Racowsky, 1985;Racowsky and Satterlie,1985).Such intimate metabolic contact between oocyte and cumulus cells is thought to play a key role in disseminating local and endocrine signals to the oocyte via the cumulus cells.Hence,an understanding of the nutritional, metabolic or hormonal factors conferring oocyte developmental competence,by necessity,must entail an examination of the COC as a whole(as opposed to isolated oocytes).However,the majority of studies investigating energy substrates for maturing oocytes involve the addition of substrates to intact COCs and determining either developmental outcome or the metabolism of the denuded oocyte.Clearly,the metabolic pro®le of denuded oocytes(DOs)differs signi®cantly from that of COCs(Colonna and Mangia,1983;Zuelke and Brackett,1993;Khurana and Niemann,2000a).Importance of cumulus cells to oocyte IVMApart from the importance of granulosa cells and cumulus cells to the oocyte throughout follicle growth,the cumulus cells also play a critical role during spontaneous meiotic maturation in vitro.At around the time of meiotic resumption,cumulus cell±TZP begin to withdraw from the oocyte and there is almost complete loss of gap-junctional communication by the time oocytes reach metaphase I(MI).Considerable extracellular production of hyaluronic acid by cumulus cells causes dispersion of cumulus cells or cumulus expansion(Eppig,1981;Salustri et al.,1989; Chen et al.,1990).However,during this phase cumulus cells presumably continue to communicate with the oocyte,as removal of the cumulus cells prior to IVF results in compromised fertilization and embryo development compared with removing them post-IVF,regardless of co-culture with cumulus cells (Zhang et al.,1995;Fatehi et al.,2002).One of the most commonly used selection criteria for IVM is the morphology of the COC,in particular the cumulus vestment.Factors such as increased cell layers and degree of compaction are related to improved developmental out-come compared with oocytes surrounded by compromised vestments and DOs(Shioya et al.,1988;Madison et al.,1992; Lonergan et al.,1994;Goud et al.,1998),as well as there being a positive relationship between increased cumulus cell number in co-culture and developmental competence(Hashimoto et al., 1998).Follicular¯uid compositionThe follicular antrum is formed early in folliculogenesis. Follicular¯uid(FF)bathes the COC and contains a variety of proteins,cytokine/growth factors and other peptide hormones, steroids,energy metabolites and other unde®ned factors. Granulosa cells are separated by20nm-diameter channels, potentially allowing molecules up to M r500000in size to enterM.L.Sutton,R.B.Gilchrist and J.G.Thompson36 by guest on July 14, 2011 Downloaded fromthe antrum (Gosden et al .,1988).The porous nature of the follicular epithelium results in FF composition being comparable with that of `®ltered'venous plasma (Table I).Protein contentMean protein concentration is signi®cantly lower in bovine FF compared with blood serum,regardless of follicle size (Desjardins et al .,1966),and this is largely accounted for by the partial exclusion of most proteins with MW >250000(i.e.a 1-lipoprotein,a 2-macroglobulin and IgM)(Andersen et al .,1976).There is a positive relationship between increasing follicle size and the concentration of proteins with high molecular weight,indicative of increased permeability of serum proteins with follicular growth.In general,the concentration of globulins in human FF are not signi®cantly different to that in plasma,while albumin is 35%higher in FF compared with plasma (Velazquez et al .,1977).The total concentrations of amino acids in FF are also higher than in blood plasma,with the exception of cysteine (0.19mmol/l in plasma versus 0.062mmol/l in FF)(Velazquez et al .,1977),possibly due to its oxidation to cystine or use by the COC.The concentration of cysteine in a commonly used medium for IVM (Tissue culture medium 199;TCM199)is 0.6m mol/l,which is 10-fold lower than physiological levels.ElectrolytesThe concentrations of electrolytes such as chloride,calcium and magnesium in FF from large follicles (mostly pre-ovulatory)are highly comparable with serum and plasma levels (Gosden et al .,1988).Potassium levels may be elevated (1.5-to 3-fold)in FF in some species (possibly indicating active transport systems)(Schuetz and Anisowicz,1974;Gosden et al .,1988).Energy substratesThe concentration of energy metabolites in human FF has been studied with samples obtained from pre-ovulatory follicles of hyperstimulated patients undergoing assisted reproduction treat-ments.One group (Leese and Lenton,1990)reported that follicular lactate levels were 3-to 4-fold higher than serum levels (6.12versus 1.5±2mmol/l)and exist in a 2:1ratio with glucose.This contradicts later studies showing that glucose and lactate levels in human FF were 3.39and 3.17mmol/l respectively (Gull et al .,1999).Differences may have arisen from the methods used for analysis of the FF and serum and the storage of samples.Glucose-6-phosphate dehydrogenase activity and lactate dehydrogenase-1(LDH-1)synthesis increase signi®-cantly with oocyte growth,plateauing in medium-sizedfolliclesFigure 1.Oocyte±cumulus cell communication.Both paracrine (bold arrow)and gap-junctional (dashed arrow)communication between the oocyte and cumulus cells are required for normal oocyte and follicle development.Both communications pathways are bi-directional.Factors transmitted via these pathways include follicular ¯uid meiosis-activating sterol (FF-MAS),cAMP,purines and pyrimidines,metabolites,amino acids,growth differentiation factor-9(GDF-9)and GDF-9B or bone morphogenic protein (BMP-15),®broblast growth factor (FGF)and activin.Cumulus±oocyte complex metabolism37by guest on July 14, 2011 Downloaded from(Mangia et al .,1976).A positive correlation between glucose utilization and lactate production exists,and it is postulated that as the follicle grows then energy requirements increase with decreasing O 2availability (due to thickening of the avascular epithelium),leading to an increase in glycolysis and increased lactate production (Boland et al .,1993;Gull et al .,1999).This is supported by a 2-fold decrease in FF O 2tension (59.8mmHg in FF versus 102mmHg in maternal blood)and higher CO 2tension (46.9mmHg in FF versus 38.3mmHg in blood),resulting in a lower pH of FF compared with blood (7.33and 7.41respectively)(Fischer et al .,1992).All of these events are associated with increasing follicular growth leading to ovulation.Follicular vascularity and dissolved O 2content in FF are positively related to oocyte developmental outcome in humans.Measurements of follicular vascularity prior to oocyte collection demonstrated that oocytes derived from follicles with >50%blood ¯ow on their circumference had signi®cantly higher rates of clinical pregnancies following IVF and embryo transfer,com-pared to oocytes with poor vascularity (Chui et al .,1997;Coulam et al .,1999).Furthermore,only embryos resulting from oocytes collected from follicles with a high degree of vascularity (blood ¯ow identi®ed on 76±100%of the follicular circumference)resulted in successful pregnancies following embryo transfer.Poor vascularity and low dissolved O 2content are associated withdevelopmental defects such as aneuploidy,abnormal spindle organization and cytoplasmic structure (Van Blerkom et al .,1997).Oocytes from follicles with higher dissolved O 2in FF are more competent than oocytes from lower oxygenated follicles (as measured by development to 6-to 8-cell stage)(Van Blerkom et al .,1997;Huey et al .,1999).These studies suggest that hypoxic conditions have adverse effects on subsequent oocyte quality.LipidsIn general,fatty acid concentration of follicular ¯uid decreases with follicle size (Yao et al .,1980).In particular,linoleic acid is negatively correlated to follicle size,and its addition to culture medium inhibits GVBD in bovine oocytes,possibly by indirectly stimulating cAMP levels by affecting adenylate cyclase activity (Homa and Brown,1992).In general,there appears to be little information on the role of lipids during oocyte growth and maturation.There is,however,an important exception to this and that is with regard to a group of sterols,the meiosis-activating sterols (MAS),that are intermediates in the cholesterol biosyn-thetic pathway.Follicular ¯uid MAS (FF-MAS)and testicular MAS (T-MAS,®rst puri®ed from testicular tissue)are present in the FF of pre-ovulatory follicles in micromolar concentrations (Byskov et al .,2002).Their potential roles in the regulation of oocyte maturation are discussed later.Table I.The composition of sheep,pig,human and cow follicular ¯uid (FF)from pooled,small or large folliclesSheep Pig Human Cow PooledPooledPCOSPost LHPooledUnstimulated (pre LH)Stimulated (post LH)SmallLarge Small Large Na +(mmol/l)149b128h 139b 133.5b 132b 177.7i 109.2i 102.7i 88.1i K +(mmol/l) 4.7b 15.9h 8.05b 4.9b 9.2b 10.2i 7.4i 11.4i 5.6i Cl ±(mmol/l)107b97.3b 124.5b 149.5b Ca 2+(mmol/l) 2.29b2.34h 2.3b 0.94b3.1b 1.9i 2.1i 2.2i 1.8i Mg 2+(mmol/l)0.89b0.75b 0.76b 0.90i 0.89i 1.3i 0.73i Protein (g/100ml) 6.84h7.28c 7.08a 6.94f247j 33j Albumin (mg/ml)48.2c 43.4i36i54.1i47.4iTotal aa (m g/ml)236cGlucose (mmol/l) 3.44d 3.39e Lactate (mmol/l) 6.27d 3.17e pO 2(mmHg)59.8g 100.5k pCO 2(mmHg)46.9g 34.8k pH7.33g 7.35kNH 4+(m mol/l)134jSuperscripts indicate references.a Desjardins et al .,1966;b Gosden et al .,1988;c Velazquez et al .,1977;d Leese and Lenton,1990;e Gull et al .,1999;fAndersen et al .,1976;g Fischer et al .,1992;h Schuetz and Anisowicz,1974;i Wise,1987;j Hammon et al .,2000;k Huey et al .,1999.PCOS =polycystic ovary syndrome.M.L.Sutton,R.B.Gilchrist and J.G.Thompson38by guest on July 14, 2011 Downloaded fromTemperature and pHTemperature gradients exist within the ovarian environment,with pre-ovulatory follicles approximately1.5±2°C cooler than the ovarian stroma in pigs(Hunter et al.,1997,2000),humans (Grinsted et al.,1985)and cows(Grùndahl et al.,1996).How such temperature gradients are established and maintained is dif®cult to explain,and may yet re¯ect inadequate technologies to make such measurements.However,no differences in tempera-ture were observed between the stromal tissue and small antral follicles(Grùndahl et al.,1996;Hunter et al.,1997).It has been argued(Hunter et al.,1997)that the variations in temperature are established due to the follicle becoming largely avascular compared to the surrounding tissue,as well as an increase in endothermic activity associated with ovulatory processes. Decreased temperatures may decrease the viscosity of porcine FF,which would facilitate entry of the oocyte into the Fallopian tubes.However,the application of temperature gradients to IVM did not alter the developmental rates of bovine oocytes(Shi et al.,1998),indicating that although the temperature used for IVM is based on visceral temperature(and is higher than that within the ovary;Grùndahl et al.,1996;Hunter et al.,1997,2000),this seems to be adequate for IVM.The adverse effects of short-term heat shock during IVM are seen when temperatures are increased by approximately4°C and for>30min culture periods(Ju et al., 1999).IVM mediaCommercially available cell culture mediaThe maturation of oocytes in vitro is typically undertaken in commercially available complex medium,originally intended for the culture of non-ovarian somatic cells.Several commercially supplied media are commonly used for the base of IVM systems, such as TCM199,Waymouth MB752/1,Ham's F-12,Minimum Essential Medium(MEM),and Dulbecco's modi®cation of Eagle's medium(DMEM).The composition of the most commonly used IVM media are given in Table II.Table II.The composition of commercially supplied media commonly used for in-vitro oocyte maturationCompound(mmol/l)MediumTCM199Waymouth MB752/1Ham's F-12MEM DMEM HECM CaCl2 1.8020.820.23 1.36 1.36 1.9 MgSO40.788 3.960.580.790.79KCl 5.367 2.013 5.37 5.373 NaCl116.359102.67130.05116.36109.51113.8 NaHCO326.661426.1944.0425 Na2HPO4 1.017 2.5 1.18 1.17 1.04DL-alanine0.5610.1L-arginine0.3320.3610.60.4DL-aspartic acid0.4510.450.10.01 Asparagine0.01 L-cysteine 6.98Q10±40.510.220.01 L-cystine0.0830.060.10.2DL-glutamic acid0.908 1.020.10.01 L-glutamine0.684 2.41240.2 Glycine0.6660.670.10.40.01 L-histidine0.1040.780.170.20.20.01 Hydroxy-L-proline0.0763DL-isoleucine0.3050.190.030.40.8DL-leucine0.9150.380.10.40.8L-lysine0.479 1.640.250.510.01 DL-methionine0.2010.340.030.10.2DL-phenylalanine0.3030.30.030.20.4L-proline0.3480.430.30.01 DL-serine0.4760.10.40.01 Taurine0.5 DL-threonine0.5040.630.10.40.8DL-tryptophan0.09790.200.010.050.08L-tyrosine0.2560.260.230.46DL-valine0.4270.560.10.40.8Glucose 5.5527.7510 5.5524.97DL-lactate 4.5 Pyruvate1Glutathione 1.62Q10±40.16Hypoxanthine0.00220.180.04TCM=tissue culture medium;MEM=Minimum Essential Medium;DMEM=Dulbecco's modi®cation of Eagle's medium;mBM-3=Basic salt medium3; HECM=hamster embryo culture medium.Cumulus±oocyte complex metabolism39 by guest on July 14, 2011 Downloaded fromA range of different IVM base media is commonly used since oocytes from different species vary in their response to different media.Bovine oocytes matured in TCM199,SFRE(serum-free medium based on TCM199)and MEM have superior blastocyst development rates(12±19%)compared with oocytes matured in Waymouth MB752/1,Ham's F-12(3%and1%respectively; Rose and Bavister,1992)or MeÂneÂzo's B2(Hasler,2000).This is contrary to murine oocytes,where the highest cleavage rates were observed with IVM systems that used Waymouth MB752/1and MEM+non-essential amino acids(NEA),Ham's F-12and a MEM(van de Sandt et al.,1990).For porcine IVM,the composition of Waymouth MB752/1more favourably supports male pronucleus formation than TCM199or TLP-PVA(Tyrode's with lactate,pyruvate and polyvinyl alcohol)media(Yoshida et al.,1992).This may be related to high cysteine and cystine levels in Waymouth MB752/1,leading to increased cytoplasmic integrity through elevated axoplasmic glutathione(GSH)levels (Yoshida et al.,1993).Given the apparent need to test the different IVM base media in different species,the choice of base medium for human IVM is particularly dif®cult.Clearly,it is not possible to conduct an experiment large enough using human oocytes to test thoroughly the different IVM media.IVM of human oocytes is typically conducted using either TCM199(Trounson et al.,1994;Cha and Chian,1998;Mikkelsen et al.,1999)or Ham's F10(Cha et al., 1991).Waymouth MB752/1has been used for IVM of marmoset monkey oocytes(Gilchrist et al.,1995,1997),while modi®ed Connaught Medical Research Laboratories medium(CMRL-1066)is the most commonly used rhesus oocyte IVM medium (Schramm and Bavister,1994,1996;Schramm et al.,1994). The use of simple inorganic salt-based media is useful in determining which of the multitude of factors in complex media are important for successful oocyte maturation.In serum-free systems,mBM-3supplemented with glucose and a mixture of11 amino acids(in particular glutamine)(Rose-Hellekant et al., 1998),or supplemented with NEA alone,or NEA+essential amino acids(EA)(Avery et al.,1998)during IVM,led to improved blastocyst development compared with that achieved with TCM199.Embryo development has also been achieved from human oocytes matured in simple balanced salt solutions,such as human tubal¯uid(HTF;Jaroudi et al.,1997;Hwu et al.,1998) and human oocyte maturation medium(HOM;Trounson et al., 1998,2001).As IVM media trials are exceptionally dif®cult using human oocytes,such experiments are more feasible using non-human primate oocytes.With appropriate amino acid additives,a simple protein-free medium such as hamster embryo culture medium-10(HECM-10)is equally effective as the complex medium,CMRL-1066during IVM,at supporting development of rhesus oocytes through to the blastocyst stage(Zheng et al., 2001b).The formulation of IVM media speci®cally based on the composition of FFs has not been attempted.Substantial improve-ments in embryo culture media have been made over the past decade by basing media formulations on the major cation and anion concentrations and metabolic substrates of reproductive tract¯uids,for example sheep oviduct¯uid(SOF;Tervit et al., 1972),HTF(Quinn et al.,1985)and G1/G2;human tubal and uterine¯uids(Gardner et al.,1996),MTF;mouse tubal¯uid (Gardner and Leese,1990)and PL3(based on bovine blood and sheep oviductal¯uid;Park and Lin,1993).IVM ef®ciency may be improved with the design of an IVM medium along similar principles.Macromolecule supplementationThere is a long-running debate as to whether protein and macromolecule supplements should be added to IVM media and subsequent IVF and in-vitro embryo culture(IVC)media. Numerous protein supplements are used(Fukui and Ono,1989; Wiemer et al.,1991)such as fetal calf serum(FCS),estrous cow serum,estrous gilt serum,anestrous cow serum,steer serum, newborn calf serum,bovine serum albumin(BSA)and for human IVM,autologous patient serum and human serum albumin.FCS and BSA are the most commonly used protein supplements in IVM,with bovine oocytes matured in the presence of FCS having higher frequencies of oocyte nuclear maturation,cleavage and blastocyst formation compared to supplementation with or without other macromolecules(Fukui and Ono,1989;Wiemer et al.,1991;OcanÄa-Quero et al.,1999;Hasler,2000).Fetal serum contains numerous factors thought to be bene®cial to oocyte maturation and embryo development such as growth factors, lipids,albumin,hormones,steroids,cholesterol,peptides and many other unde®ned factors.The highly unde®ned nature of protein supplements makes them undesirable for many research aspects,due to the risk of batch variation and contaminating compounds of unde®ned nature.Although high-grade BSA has some degree of variability,it is less variable than serum itself. BSA has also been shown to contain steroids,especially estradiol, at levels high enough to allow for adequate cytoplasmic and nuclear maturation that supplementation with estradiol alone is unnecessary(Mingoti et al.,2002).Polyvinyl alcohol(PVA)and polyvinyl pyrolidone(PVP)are commonly used non-biological alternatives to protein supple-ments to aid in the handling of oocytes and embryos.Although oocytes matured in media supplemented with PVA or PVP have lower rates of polyspermic fertilization,development to the blastocyst stage is compromised compared with that of oocytes matured in the presence of proteins(Eckert and Niemann,1995; Fukui et al.,2000).Despite this,supplementation of PVA-based IVM media with hormones(LH,FSH and estradiol),growth factors(epidermal growth factor)and other bene®cial factors(b-mercaptoethanol,hypotaurine)can increase blastocyst develop-ment to rates comparable with oocytes matured in the presence of proteins(Avery et al.,1998;Abeydeera et al.,2000;Mizushima and Fukui,2001).This indicates that inorganic macromolecules together with de®ned protein additives can potentially replace serum/BSA supplements in IVM medium.FF as a mediumWhen FF is used as a substitute for serum in IVM media,embryo development is not in¯uenced by the size of the follicle from which the¯uid originated,nor are there any differences between bovine oocytes matured in the presence of FF or serum(Lonergan et al.,1994;Carolan et al.,1995;Kim et al.,1996).Although the size of the follicle from which the FF is sourced has little in¯uence on embryo development,¯uid obtained from non-atretic follicles supported oocyte developmental competence to a greater extent than FF from atretic follicles(CognieÂa et al.,1995).In contrast,FF from non-atretic dominant follicles when added toM.L.Sutton,R.B.Gilchrist and J.G.Thompson40 by guest on July 14, 2011 Downloaded from。
![用作嗜中性白细胞弹性蛋白酶抑制剂的2-吡啶酮衍生物及其用途[发明专利]](https://img.taocdn.com/s1/m/0462effdff00bed5b8f31da5.png)
专利名称：用作嗜中性白细胞弹性蛋白酶抑制剂的2－吡啶酮衍生物及其用途
专利类型：发明专利
发明人：彼得·汉森,卡罗里娜·劳威兹,汉斯·洛恩,安东尼奥斯·尼基蒂迪斯
申请号：CN200480027517.4
申请日：20040915
公开号：CN1856467A
公开日：
20061101
专利内容由知识产权出版社提供
摘要：本发明提供了新颖的式(I)的化合物以及其光学异构体、外消旋体以及互变体，以及其可药用盐，其中R、R、R、R、G、G、L、Y和n如说明书中定义；以及其制备方法、包含这些化合物的组合物以及其在治疗中的用途。
所述的化合物为嗜中性白细胞弹性蛋白酶抑制剂。
申请人：阿斯利康(瑞典)有限公司
地址：瑞典南泰利耶
国籍：SE
代理机构：北京市柳沈律师事务所
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Zevalin在欧盟获批准
李卫华
【期刊名称】《国外药讯》
【年(卷),期】2004(000)005
【总页数】1页(P30)
【作者】李卫华
【作者单位】无
【正文语种】中文
【中图分类】R95
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5.百济神州Brukinsa获欧盟批准:治疗华氏巨球蛋白血症(WM) [J],
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DOI:10.12280/gjszjk.20200730谢奇君，李欣，赵纯，凌秀凤△【摘要】辅助生殖技术（ART）已被广泛应用于不孕症的治疗，包括人工授精（AI）和体外受精-胚胎移植（IVF-ET），及其相关衍生技术如胞浆内单精子注射（ICSI）、胚胎植入前遗传学筛查（PGS）、卵母细胞体外成熟（IVM）、胚胎辅助孵化（AH）等技术。
随着ART的普及和妊娠率的逐步提高，其带来的并发症及其安全性也越来越受到重视。
能够及时发现和处理并发症，可以最大限度地使不孕症患者获得安全优质的妊娠结局。
目前，ART相关并发症发生的原因仍存在争议，有部分研究认为是由于ART导致的多胎妊娠或不孕症病因，也有研究认为是由于ART本身。
故对近年来相关文献进行分析，总结ART相关并发症的最新研究进展。
【关键词】生殖技术，辅助；并发症；不育，女（雌）性；体外受精；胚胎移植Research Progress of Complications Related to Assisted Reproductive Technology XIE Qi-jun,LI Xin,ZHAO Chun,LING Xiu-feng.Reproductive Center,Women′s Hospital of Nanjing Medical University(NanjingMaternity and Child Health Care Hospital),Nanjing210004,ChinaCorresponding author:LING Xiu-feng,E-mail:************************【Abstract】Assisted reproductive technology(ART)has been widely used in the treatment of infertility,including artificial insemination(AI)and in vitro fertilization-embryo transfer(IVF-ET),and many derivativetechniques such as intracytoplasmic sperm injection(ICSI),preimplantation genetic screening(PGS),in vitromaturation(IVM),and assisted hatching(AH).With the popularity of ART and the gradual improvement ofpregnancy rate,more and more attention has been paid to the complications of ART and the safety of ART.Detection and treatment of complications in time can maximize the safety and high quality of pregnancy,and thegood outcomes for patients.At present,the causes of ART-related complications are still controversial.Somestudies believe that the increased rate of multiple pregnancy caused by ART or the factors related to infertility arethe main causes.However,other studies believe that the factors of ART itself cannot be overlooked.In this review,we analyzed the complications related to ART and the causes.【Keywords】Reproductive techniques，assisted；Complications；Infertility，female；Fertilization in vitro；Embryo transfer（ＪＩｎｔＲｅｐｒｏｄＨｅａｌｔｈ蛐ＦａｍＰｌａｎ，2021，40：204-208）·综述·基金项目：国家自然科学基金（81871210）作者单位：210004南京医科大学附属妇产医院（南京市妇幼保健院）生殖中心通信作者：凌秀凤，E-mail：************************△审校者辅助生殖技术（assisted reproductive technology，ART）是一种应用各种技术处理精子或卵子，以帮助不孕症夫妇实现生育的方法，包括人工授精（artificial insemination，AI）、体外受精-胚胎移植（invitro fertilization-embryo transfer，IVF-ET）及相关技术，如胞浆内单精子注射（intracytoplasmic sperminjection，ICSI）、胚胎植入前遗传学筛查（preimplantation genetic screening，PGS）、卵母细胞体外成熟（in vitro maturation，IVM）、胚胎辅助孵化技术（assisted hatching，AH）和卵母细胞玻璃化冷冻技术等。
源自马来西亚制龙药业GENOPHARMA的胸部保养神器宇宙D'EVEREST无论是A CUP还是D CUP，乳房对于每一个女人都是一样的重要。
因为她象征着女人的阴柔，更是母性无条件爱的标志。
它对我们的意义是如此重要，我们当然要好好维护她的健康。
乳腺增生，一种全世界每年有50万人死于某种可怕的疾病的前兆，基于有人称它为乳腺癌的“癌前病变”，你不要小看它。
乳腺增生是一种妇科常见的疾病。
多发于25-39岁左右的中年妇女，因为这段时间是女性性机能最旺盛的时期。
表现为乳房的不同部位单发或多发地生长一些肿块，质地柔软，边界不清，可活动，常伴有不同程度的疼痛。
尤其在月经前、劳累后或是生气(中医称气郁)等情绪波动时，肿块增大，疼痛加重，而在月经后肿块明显缩小，疼痛减轻近些年来该病发病率呈逐年上升的趋势，年龄也越来越低龄化。
乳腺增生症是正常乳腺小叶生理性增生与复旧不全，乳腺正常结构出现紊乱，属于病理性增生，它是既非炎症又非肿瘤的一类病。
权威资料显示：西方妇女乳腺癌的发病高峰期为60-70岁。
中国女性的乳腺癌发病高峰则在40-50岁。
据卫生调查数据显示，我国乳腺病年龄比欧美平均年轻10-15岁，20岁左右女性要注意防腺纤维瘤，其发生与雌激素相对或绝对升高有密切关系。
30岁的女性则患乳腺增生，这个年龄阶段女性内分泌系统影响因素较多，如情绪不稳定，过度劳累或食用有激素的食品，容易产生乳腺增生。
宇宙高峰采用传统草药加以10倍热萃取技术，使草药发挥之至的同时又有效的过滤草药本身残留的农药化学物及重金属。
最为突出的纳米科技使有效成份转化成小分子量，加快身体吸收及新陈代谢功能，有效双向调节人体内分泌，使乳腺患者的雌激素水平达到最佳平衡点，从而对乳房肿块、结节起到软坚散结，止痛消节的积极作用。
宇宙高峰内含葛雌素能有效调节雌激素，使用3天可缓解疼痛，15天消除乳房各类疼痛，30 天软化分解乳房肿块，50天重建乳房健康屏障，从根本上彻底解决雌激素紊乱，平衡雌二酮沉淀，确保乳腺增生、钎维瘤不再二次复发。
O cultivo in vitro tem propiciado a propagação massal de uma série de espécies de orquídeas em risco de extinção ou de elevado valor comercial (Santos et al., 2006). Os meios assim-bióticos para orquidáceas, além de propiciar a germinação, também devem possibilitar o crescimento e muitas vezes o desenvolvimento das espécies culti-vadas. A maioria deles são complexos, contendo diversos nutrientes, vitaminas e reguladores de crescimento (Ventura et al.,2002), os quais elevam os custos da propagação.Para atender às necessidades de cada espécie, mudanças nos meios de cultura para orquídeas têm sido estudadas. Faria et al. (2004) verificaram que a adição de 60 g L-1 de sacarose no meio MS (Murashige & Skoog, 1962) proporcionou maior crescimento e taxade multiplicação de mudas de D. nobile.Pasqual et al. (2009) constataram aviabilidade de multiplicação in vitrode outra espécie de orquídea, Cattleyalodigesii, com a utilização de meio KC(Knudson, 1946) líquido enriquecidocom polpa de banana nanica. Cardoso& Ono (2011) concluíram que autilização de 1,0 mg L-1 de BAP ede KNO3e NH4NO3, na metade daconcentração recomendada para o meioMS, é eficiente para a multiplicação daorquídea Brassocattleya. Pasqual etal. (2011) verificaram que a adição desilício em meio MS propiciou ausênciade deformações foliares em plântulasde orquídeas. Entretanto, é importantereduzir os custos dos meios de cultura.Visando a facilidade de formula-ção, baixo custo e acessibilidade doscomponentes, Campos (2002) propôsum meio alternativo, no qual a maioriadas espécies de orquídeas germina ecresce. Para redução dos custos, estudoscom produtos orgânicos (água de coco,banana, mamão, milho) adicionados aosmeios de cultura convencionais foramrealizados (Martínez & García, 2007;Araújo et al., 2006b; Vieira et al., 2009;Campos, 2010). Esses produtos orgâni-cos são também fontes de aminoácidos,vitaminas, sais minerais e reguladores decrescimento, que são os componentesmais onerosos dos meios de cultura,segundo Araújo et al. (2006a).Dentre eles, a água de coco começoua ser adicionada em meios nutritivos hámais de meio século por Overbeek et al.(1941). Segundo Aragão et al. (2001),SOARES JS; ROSA YBCJ; SUZUKI RM; SCALON SPQ; ROSA JUNIOR EJ. 2013. Cultivo in vitro de Dendrobium nobile com uso de água de coco no meio de cultura. Horticultura Brasileira 31: 63-67.Cultivo in vitro de Dendrobium nobile com uso de água de coco no meio de culturaJackeline S Soares1; Yara BCJ Rosa1; Rogério M Suzuki2; Silvana PQ Scalon1; Edgard J Rosa Junior11UFGD-FCA, Rod. Dourados-Itaum km 12, 79804-970 Dourados-MS; jacke.schultz@; yararosa@.br; silvanascalon@.br; edgardjunior@.br; 2IBt/SP, C. Postal 68041, 04045-972 São Paulo-SP; rogeriosuzuki@RESUMOA água de coco é um dos componentes orgânicos de baixo custo mais utilizados nos meios de cultura para cultivo in vitro de plantas, mas poucas são as informações sobre seus efeitos em orquídeas, onde esse tipo de propagação é utilizado. Assim, objetivou-se estudar as quantidades de água de coco acrescidas ao meio de cultura quanto aos seus efeitos na germinação e crescimento in vitro de Dendrobium nobile. Foi utilizado o delineamento experimental inteiramente ca-sualizado, com três repetições, e os tratamentos compostos de cinco volumes de água de coco (0; 50; 100; 150 e 200 mL L-1), que foram adicionados ao meio de cultura. Foram utilizadas como material de estudo sementes de D. nobile produzidas mediante autopolinização manual.Após a semeadura, as culturas permaneceram por seis meses em sala de crescimento com temperatura e fotoperíodo controlados(12 horas, 1000 lux; 23°C + 2) quando as plântulas foram avaliadas.A adição de 200 mL L-1 de água de coco ao meio de cultura propiciou os melhores resultados para comprimento, diâmetro e número dos pseudobulbos, número de folhas, número de raízes, comprimento de raízes e massa fresca de D. nobile, não influenciando apenas a porcentagem de germinação e o número de plântulas produzidas.Palavras-chave: Orchidaceae, meio de cultura, cultivo in vitro.ABSTRACTIn vitro cultivation of Dendrobium nobile using coconut water in the culture mediumCoconut water is one of the inexpensive organic components most utilized in culture media for in vitro cultivation of plants, but there are few informations about its effect in orchids, where this kind of propagation is used. The objective of this research was to study the effects on germination and growing of Dendrobium nobile when coconut water is added to the in vitro culture medium. We used a completely randomized design, with three replications; the treatments consisted of adding five volumes of coconut water (0, 50, 100, 150 and 200 mL L-1) to the culture medium. Seeds of D. nobile, obtained by manual pollination were used as study material. After sowing, the cultures stayed for six months in a growth chamber with controlled temperature and photoperiod (12 hours/1000 lux; 23°C±2), when the seedlings were evaluated. The addition of 200 mL L-1 of coconut water to the culture medium provided the best results for length diameter and number of pseudobulbs, number of leaves, number of roots, length of roots and fresh weight of D. nobile, not influencing only the germination percentage and the number of seedlings produced.Keywords: Orchidaceae, culture medium, in vitro cultivation.(Recebido para publicação em 21 de novembro de 2011; aceito em 4 de fevereiro de 2013) (Received on November 21, 2011; accepted on February 4, 2013)a água de coco, que é o endosperma de Cocus nucifera, apresenta em sua composição básica 93% de água, 5% de açúcares, além de proteínas, vitaminas e sais minerais, grau brix igual a 7,0 (21ºC) e pH em água igual a 4,8. Cada 100 mL de água de coco contém 4,4 g de glicose; 0,37 mg de proteínas: 6,2 mg de fósforo; 175 mg de potássio;17,5 mg de cálcio; 8,5 mg de magnésio; 10,5 mg de sódio; 0,06 mg de ferro e 57 mg de vitamina C.A concentração de água de coco utilizada na composição dos meios de cultura é de 3 a 15% para um grande número de espécies vegetais cultivadas in vitro. Ela é utilizada para estimular o crescimento de calos, aumentar a ger-minação assimbiótica, formar embriões somáticos, induzir a divisão de grãos de pólen e o desenvolvimento de embriões imaturos (Caldas et al., 1998).Embora seja o componente orgânico mais utilizado no enriquecimento de meios de cultura, seus efeitos em relação à promoção da germinação, crescimento e desenvolvimento in vitro de orquídeas necessitam ser mais estudados uma vez que é constituída por diversas classes de hormônios vegetais tais como ácido indol acético, ácido indol butírico, áci-do abcísico, ácido giberélico, zeatina, benzil adenina, ácido naftalenoacético e ácido diclorofenoxiacético (Ma et al., 2008), os quais influenciam as diferentes fases do desenvolvimento vegetal. O efeito benéfico da adição de água de coco pode ser explicado pelos elevados teores de glicose, frutose e sais minerais, além de hormônios vegetais, necessários ao processo de formação e desenvolvimento das plântulas (Nunes et al., 2008). Além disso, deve-se con-siderar também o status nutricional e hormonal endógeno de cada material de estudo, ressaltando a necessidade de estudos específicos em relação à espécie vegetal de interesse bem como ao pro-pósito de sua utilização na promoção quer da germinação, organogênese ou embriogênese in vitro.Objetivou-se estudar a quantidade de água de coco acrescida ao meio de cul-tura de Campos (2002) quanto aos seus efeitos na germinação e crescimento in vitro de Dendrobium nobile.MATERIAL E MÉTODOSO experimento foi realizado nolaboratório de cultivo in vitro da Fa-culdade de Ciências Agrárias (FCA)da Universidade Federal da GrandeDourados (UFGD). O delineamentoexperimental foi inteiramente casuali-zado, sendo os tratamentos compostosde cinco volumes de água de coco (0;50; 100; 150 e 200 mL L-1), que foramadicionados ao meio de cultura e trêsrepetições. A parcela experimental foicomposta de um frasco de meio de cul-tura. Foram utilizadas como material deestudo sementes de Dendrobium nobileproduzidas mediante autopolinizaçãomanual, cedidas pelo Orquidário daFCA. Cápsulas maduras foram coletadase as sementes provenientes destas, foramretiradas, homogeneizadas, pesadas e,0,005 g submetidas ao teste de tetrazóliopara determinação da viabilidade. Apósa confirmação da viabilidade procedeu--se à semeadura in vitro.Utilizou-se o meio de cultura pro-posto por Campos (2002), modificadopela utilização de 70 g de tomate semcasca e sementes, 50 g de banana na-nica sem casca, 3 mL de adubo NPKna formulação 10-10-10, 17 g de ágarbacteriológico, 25 g de açúcar cristal, 3g de carvão ativado, água de coco nosvolumes 0; 50; 100; 150 e 200 mL L-1 eágua destilada para completar um litro.Optou-se pela utilização deste meioalternativo pela facilidade de aquisiçãode seus componentes e pelo baixo custo,o que o torna acessível aos produtores.Após homogeneização no liqui-dificador, o pH foi ajustado para 5,0com KOH e 80 mL do meio de culturafoi transferido para frascos de 600 mLprovidos de tampa metálica, sendo, aseguir, esterilizados em autoclave por20 minutos a 120°C e uma atmosferade pressão. Em seguida à esterilizaçãoe solidificação do meio, os frascos fo-ram transferidos para câmara de fluxolaminar, previamente esterilizada comluz germicida por 30 minutos, para rea-lização da semeadura in vitro.Cada porção de 10 mg de sementesfoi transferida para erlenmeyer e desin-festada por 15 minutos em uma soluçãocomposta por 3 mL de hipoclorito desódio (2,5%) e 6 mL de água destiladaesterilizada em autoclave (Campos,2002). Decorrido este tempo, a suspen-são foi diluída para 50 mL com águadestilada estéril, no interior da câmarade fluxo laminar. Cada frasco recebeu,com a utilização de pipetador automá-tico, 2 mL da suspensão de sementes(aproximadamente 800 sementes viá-veis). Foram utilizados três frascos paracada tratamento.Após a semeadura os frascos foramtampados e lacrados com filme plásti-co, sendo acondicionados em sala decrescimento com temperatura médiade 23°C±2 e fotoperíodo de 12 horas,com intensidade luminosa de 1.000lux, obtida por meio de duas lâmpadasfluorescentes de 40W cada.Decorridos seis meses, foram con-tabilizadas as plântulas e os protocor-mos produzidos. A germinação (%)foi calculada levando-se em conta onúmero de protocormos e plântulasexistentes em relação ao número médiode sementes viáveis inoculado em cadafrasco. Já para o número de plântulasforam consideradas apenas as plântulasque apresentassem sistema radiculare parte aérea identificáveis a olho nu.Após a completa remoção do substrato,26 plântulas de cada frasco, selecionadasaleatoriamente, foram avaliadas quantoà massa fresca, comprimento, diâmetroe número de pseudobulbos, número defolhas, número de raízes e comprimentode raízes.As variáveis foram submetidas àanálise de variância e, em função dosresultados obtidos, foi feita a análise deregressão (Banzato & Kronka, 1992)com a utilização do SISV AR 5.3 (Fer-reira, 2010).RESULTADOS E DISCUSSÃOAs concentrações de água de cocoadicionadas ao meio de cultura influen-ciaram todas as variáveis avaliadas,exceto a germinação (%) e o número deplântulas de D. nobile, que apresentaramos valores médios de 53,4% e 170,9plântulas.O número de pseudobulbos aumen-tou em função das doses de água de cocoadicionadas, atingindo valores (calcula-dos) de 2,5 pseudobulbos/plântula com JS Soares et al.maiores. Já para espécies de outrasfamílias botânicas, como o pinhão--manso (Jatropha curcas ), o aumento das concentrações de água de coco até, o máximo de 250 mL L -1, propiciouefeito linear crescente no número defolhas por plântula (Nunes et al ., 2008),conforme o presente experimento. As diferenças entre esses dados e de outros experimentos podem ser decorrentes da especificação dos meios de cultura para cada espécie, vez que diferentescombinações de carboidratos, sais minerais, vitaminas e reguladores de crescimento estimulam, ou não, o cres-cimento de órgãos, tecidos ou células eo desenvolvimento da planta (George etal ., 2008). Entretanto, o aumento linear do número de folhas de D. nobile pode ser atribuído, principalmente, à cinetina,hormônio existente na água de coco(Ge et al ., 2005), que atua na emissão eexpansão foliar (Sobieszczuk-Nowicka et al ., 2009).De maneira análoga ao número defolhas e de pseudobulbos, o comprimen-to dos pseudobulbos também apresentou efeito linear crescente, sendo o maiorcomprimento calculado (2,2 cm) obtidocom a utilização de 200 mL L -1 de água de coco (Figura 1C). Já o diâmetro dos pseudobulbos apresentou resposta qua-drática. Os menores valores calculadospor meio da derivação da equação (0,3 cm) foram obtidos com 81,6 mL L -1 e os maiores valores (0,7 cm) com 200 mL L -1 de água de coco acrescidos aomeio de cultura (Figura 2A). A ausên-cia de água de coco no meio de culturareduziu, aproximadamente, 40 e 30% o comprimento de pseudobulbos e o seudiâmetro, respectivamente, em relação ao uso de 200 mL L -1 (Figura 2).Resultados similares foram obtidos por Simões et al . (1999) que observaram maior crescimento in vitro da parte aérea das espécies de orquídeas Epidendrumsp. e Dendrobium sp. em meio KC contendo 100 mL L -1 de água de coco, que foi a maior concentração estudada. Martínez & García (2007) relataram que os melhores resultados para com-primento da parte aérea das plantas de Stanhopea tigrina (Orchidaceae), foram obtidos com as maiores concentrações,adicionadas ao meio MS, de água de coco (120 mL L -1) e de polpa de bananae (C) comprimento de pseudobulbos (CB) de plantas de D. nobile , em função dos volumes deágua de coco utilizados [estimated values of (A) number of pseudobulbs (NB), (B) numberof leaves (NF) and (C) pseudobulbs length (CB), in plants of D. nobile , depending on thevolumes of coconut water used]. Dourados, UFGD, 2010.crescente com as concentrações de água de coco, tendo atingido valor médio de 6,9 folhas por plântula na maior concen-tração (Figura 1B). Estudos realizados por Araújo et al . (2006b) relataram que o maior número de folhas (8,3 plântula -1) de Cattleya loddigesii ‘Grande’ x Cat-tleya loddigesii ‘Alba’ foi obtido com a adição de 100 mL L -1 de água de coco ao meio KC, sendo reduzido com doses 200 mL L -1(Figura 1A). Resultados se-melhantes foram relatados por Martínez & García (2007) que obtiveram maior número de pseudobulbos de Stanhopea tigrina (Orchidaceae) com a combina-ção de 120 mL L -1 de água de coco com 100 g de banana em meio de cultura MS, sendo esta a maior concentração utilizada pelos autores.O número de folhas também foi Cultivo in vitro de Dendrobium nobile com uso de água de coco no meio de culturaOs menores valores para o com-primento de raízes (4,5 cm) foram registrados na ausência da água de coco (Figura 2C). Foi notado incremento até a maior concentração utilizada (200 mL L -1) que propiciou o maior comprimento calculado de raiz (5,4 cm). O aumento de água de coco no meio de cultura pode ser considerado benéfico ao comprimento de raiz, con -forme também mostraram Vieira et al . (2009) para Cattleya labiata x Cattleya forbesii. Eles observaram os melhores resultados para altura da parte aérea e comprimento de raízes com 100 mL L -1 de água de coco (maior concentração utilizada) e, na sua ausência, foram registrados os menores valores destas características. Como citado anterior-mente, há muitos hormônios presentes na água de coco, inclusive auxinas, que estão envolvidas em vários processos metabólicos das plantas, principalmente no crescimento. Essas substâncias fazem parte do processo de ramificação tanto da parte aérea (no caso das orquídeas o número de pseudobulbos) quanto das raízes (Berleth et al ., 2004). Embora não tenham sido analisados tais compostos, isso poderia justificar o aumento linear no número de pseudobulbos e de raíportamento linear crescente também foi observado para a massa fresca da parte aérea de D. nobile em relação aos volumes de água de coco, sendo os maiores valores (0,5 g) propi-ciados com 200 mL L -1 de água de coco (Figura 3). Araújo et al . (2006b) também registraram maiores valores para massa fresca de Cattleya loddigesii ‘Grande’x Cattleya loddigesii ‘Alba’ com o maior volume de água de coco estudado (200 mL L -1) combinados com 100 g L -1 de polpa de banana. Acréscimos de 200% em massa fresca de plântulas de Cattleya labiata x Cattleya forbesii também fo-ram relatados por Vieira et al . (2009), utilizando 100 mL L -1 de água de coco e 100 g L -1 de polpa de banana em meio MS. Incrementos de 55% em relação à testemunha também foram registrados na produção de massa fresca de Cattleya amethystoglossa por Dronk (2004) com 150 mL L -1 de água de coco e 150 g L -1 de polpa de banana nanica e no meio de cultura.Embora a utilização de água de coco(NR) e (C) comprimento de raízes (CR) de plantas de D. nobile , em função dos volumes de água de coco utilizado [estimated values of (A) diameter of pseudobulbs (DB), (B) number of roots (NR) and (C) root length (CR) in plants of D. nobile , depending on the volumes of coconut water used]. Dourados, UFGD, 2010.concordantes com aqueles obtidos por Araújo et al . (2006b). Esses autores obtiveram o maior número de raízes (6,5 plântula -1) de Cattleya loddigesii ‘Grande’ x Cattleya loddigesii ‘Alba’, utilizando o meio de cultura KC, acres-cido de 200 mL L -1 de água de coco combinado com 100 g L -1 de polpa de banana.(100 g L -1).De modo semelhante à parte aérea, a adição de água de coco ao meio de cultura teve efeitos benéficos sobre o sistema radicular. Os maiores números calculados de raízes por plântula (5,6) foram observados com 200 mL L -1 de água de coco e os menores (4,1) na sua ausência (Figura 2B). Estes dados sãoJS Soares et al.não promova alteração no número de plântulas e germinação (%) de D. nobile, a adição de 200 mL L-1 de água de coco ao meio de cultura propicia os melhores resultados para comprimento de pseudo-bulbos, comprimento de raízes, número de raízes, número de pseudobulbos, nú-mero de folhas e massa fresca de plantas, sendo este volume recomendado para germinação assimbiótica de D. nobile.AGRADECIMENTOSAo Fundect-MS pelo apoio financei-ro e ao Prof. Walmes Marques Zeviani, do Depto. de Estatística da UFPR pelo auxílio na análise dos dados.REFERÊNCIASARAGÃO WM; ISBERNER IV; CRUZ EMO.2001. Água de coco. Aracaju: Embrapa CPATC/ Tabuleiros Costeiros, Série Documentos 24. 32p.ARAUJO AG; PASQUAL M; SILVA AB;VILLA F; ROCHA HS; COSTA FC. 2006a.Propagação in vitro de plântulas de orquídea em diferentes meios de cultura e concentrações de citocinina. Plant Cell Culture and Micropropagation 2: 68-73.ARAUJO AG; PASQUAL M; VILLA F; COSTA FC. 2006b. Água de coco e polpa de banana no cultivo in vitro de plântulas de orquídea.Revista Ceres, 53: 608-613.BANZATO DA; KRONKA SN. 1992.Experimentação agrícola. 2.ed. Jaboticabal: FUNEP. 247p.BERLETH T; KROGAN NT; SCARPELLA E.2004. Auxin signals - turning genes on and turning cells around. Current Opinion in PlantBiology 7: 553-563.CALDAS LS; Haridasan P; Ferreira ME. 1998.Meios nutritivos. In: TORRES AC; CALDASLS; BUSO JA (eds). Cultura de tecidos etransformação genética de plantas. Brasília:EMBRAPA/ CNPH. p.87-132.CAMPOS DM. 2002. Orquídeas: manual práticode cultura. 3. ed. Rio de Janeiro: Expressão eCultura. 143p.CAMPOS DM. 2010. Reprodução por sementesem laboratório caseiro. 1.ed. Rio de Janeiro:Expressão e Cultura. 100p.CARDOSO JC; ONO EO. 2011. In vitro growthof Brassocattleya orchid hybrid in differentconcentrations of KNO3, NH4NO3andbenzylaminopurine. Horticultura Brasileira29: 359-363.DRONK AG. 2004. Meios de cultura e condiçõesde luminosidade para o cultivo in vitro deCattleya amethystoglossa Linden & Rchib. f.Curitiba: UFPR. 30p (Tese mestrado).FARIA RT; RODRIGUES FN; OLIVEIRA VRO;MÜLLER C. 2004. In vitro Dendrobium nobileplant growth and rooting in different sucroseconcentrations. Horticultura Brasileira 22:780-783.FERREIRA DF. 2010. Programa de análisesestatísticas (Statistical Analysis Software) eplanejamento de Experimentos - SISV AR 5.3.Universidade Federal de Lavras.GE L; YONG JWH; GOH NK; CHIA LS;TAN SN; ONG ES. 2005. Identificationof kinetin and kinetin riboside in coconut(Cocus nucifera L.) water using a combinedapproach of liquid chromatography-tandemmass spectrometry, high performance liquidchromatography and capillary electrophoresis.Journal of Chromatography 829: 26-34.GEORGE EF; HALL MA; DE KLERK GJ. 2008.Plant propagation by tissue culture. v.1 TheBackground, 3rd edition. Springer, Dordrecht,501 p.KNUDSON L. 1946. A new nutrient solutionfor the germination of orchid seed. AmericanOrchid Society Bulletin, 14: 214-217.MA Z; GE L; LEE ASY; YONG JWH; TANSN; ONG ES. 2008. Simultaneous analysisof different classes of phytohormones incoconut (Cocus nucifera L.) water using highperformance liquid chromatography and liquidchromatography–tandem mass spectrometryafter solid-phase extraction. Analytica ChimicaActa 610: 274-281.MARTÍNEZ DM; GARCÍA RAM. 2007. Efectode los compuestos orgánicos en la propagaciónin vitro de Stanhopea tigrina bateman(Orchidaceae). Foresta Veracruzana 9: 27-32.MURASHIGE T; SKOOG F. 1962. A revisedmedium for rapid growth and bioassays withtobacco tissue cultures. Physiologia Plantarum15: 473-497.NUNES CF; DALILHIA MP; SANTOS N;CUSTÓDIO TN; ARAÚJO AG. 2008.Diferentes suplementos no cultivo in vitrode embriões de pinhão-manso. PesquisaAgropecuária Brasileira 43: 9-14.OVERBEEK J; CONKLIN ME; BLAKESLEEAF. 1941. Factors in coconut milk essential forgrowth and development of very young Daturaembryos. Science 94: 350-351.PASQUAL M; FIGUEIREDO MA; REZENDEJC; ARAÚJO AG; SANTOS FC; FERREIRAEA; JUNQUEIRA KP. 2009. Fontes denitrogênio, polpa de banana e ágar nodesenvolvimento in vitro de plântulas deorquídea. Horticultura Brasileira 27: 211-216.PASQUAL M; SOARES JDR; RODRIGUES FA;ARAUJO AG; SANTOS RR. 2011. Influênciada qualidade de luz e silício no crescimentoin vitro de orquídeas nativas e híbridas.Horticultura Brasileira 29: 324-329.SANTOS AF; VENTURA GM; DIAS JMM;GOULART MS; NOV AIS RF; CECON PR;TEIXEIRA SL; MOURA E. 2006. Otimizaçãoda propagação de Sophronitis coccinea(Orchidaceae) considerando meios de cultivocom adição de carvão ativado. Horta 46: 8-12.SIMÕES FC; PAIV A PDO; RODRIGUES TM.1999. Efeito de diferentes meios de cultura,água de coco e carvão ativado na propagaçãoin vitro de meristemas de Epidendrum sp.e Dendrobium sp. In 12 CONGRESSOBRASILEIRO DE FLORICULTURA EPLANTAS ORNAMENTAIS. Anais...Jaboticabal: SBFPO. p.109.SOBIESZCZUK-NOWICKA E; WIECZOREKP; LEGOCKA J. 2009. Kinetin affectsthe level of chloroplast polyamines andtransglutaminase activity during senescenceof barley leaves. Acta Biochimica Polonica56: 255-259.VENTURA GM; DIAS JMM; TEIXEIRA LS;CARV ALHOS SV; MOTOIKE YS; NOV AISFR; CECON RP. 2002. Organogênese in vitroa partir de gemas apicais e axilares de plantasadultas de orquídeas do grupo Cattleya.Revista Ceres 47: 613-628.VIEIRA JGZ; UNEMOTO LK; Y AMAKAMI JK;NAGASHIMA GT; FARIA RT; AGUIAR RS.2009. Propagação in vitro e aclimatização deum híbrido de Cattleya Lindl. (Orchidaceae)utilizando polpa de banana e água de coco.Científica 37: 48-52.Figura 3. Valores estimados da massa fresca (MF) de plantas de D. nobile, em função dosvolumes de água de coco utilizados [estimated values of fresh weight (MF) of plants of D.nobile, depending on the volumes of coconut water used]. Dourados, UFGD, 2010.Cultivo in vitro de Dendrobium nobile com uso de água de coco no meio de cultura。
