最新再将新颖锁阳、生姜、喷鼻菇、羊肉一...课件PPT.ppt 49页

'进入夏天，少不了一个热字当头，电扇空调陆续登场，每逢此时，总会想起那一把蒲扇。蒲扇，是记忆中的农村，夏季经常用的一件物品。　　记忆中的故乡，每逢进入夏天，集市上最常见的便是蒲扇、凉席，不论男女老少，个个手持一把，忽闪忽闪个不停，嘴里叨叨着“怎么这么热”，于是三五成群，聚在大树下，或站着，或随即坐在石头上，手持那把扇子，边唠嗑边乘凉。孩子们却在周围跑跑跳跳，热得满头大汗，不时听到“强子，别跑了，快来我给你扇扇”。孩子们才不听这一套，跑个没完，直到累气喘吁吁，这才一跑一踮地围过了，这时母亲总是，好似生气的样子，边扇边训，“你看热的，跑什么？”此时这把蒲扇，是那么凉快，那么的温馨幸福，有母亲的味道！　　蒲扇是中国传统工艺品，在我国已有三千年多年的历史。取材于棕榈树，制作简单，方便携带，且蒲扇的表面光滑，因而，古人常会在上面作画。古有棕扇、葵扇、蒲扇、蕉扇诸名，实即今日的蒲扇，江浙称之为芭蕉扇。六七十年代，人们最常用的就是这种，似圆非圆，轻巧又便宜的蒲扇。　　蒲扇流传至今，我的记忆中，它跨越了半个世纪，也走过了我们的半个人生的轨迹，携带着特有的念想，一年年，一天天，流向长长的时间隧道，袅再将新颖锁阳、生姜、喷鼻菇、羊肉一... Whydiabetes(type1)andCD?Commongeneticbackground(HLA-markerDQ2,DQ8))Bothhaveincreasedgutpermeability(causedbyaproteinmodulatorcalledzonulin),presenteveninpre-diabetes(70%),severalyearsbeforeonset(inaverage3.5years).SaponeA.Diabetes2006;55:1443-49.AlltfrånSchoberEarly(<3months)introductionofglutenincreasedriskofdevelopingdiabetes6-to9-fold.Norris,JM.JAmMedAssoc2003;290:1713-20.ZieglerAG.JAmMedAssoc2003;290:1721-28.Late(>6months)introductionofglutenisariskfactorfordevelopingantibodiesprecedingdiabetesWahlbergJ.BrJNutrition2006;95:603-08.22;022 Zonulin-keepingthingsinandoutoforderinthegutBloodvesselIntestineEndothelialcellsTightjunctionCholerabacteriaZottoxinDiarrhea!!➠BacteriaareflushedoutThezonulinsystemBloodvesselIntestineZonulinDiarrhea!!Activatedby:PrematurityAnybacteria(evendead!)Toxins(foodpoisoning)RadiationChemotherapyFasanoA.Gut2001;49:159-62.90%ofabsorbedproteinsareconvertedtopeptidesthattheimmunesystemwillnotreacttoWhitebloodcell22;023 TheCDIcebergModelMostcasesofCDareundiagnosedUNDIAGNOSEDDIAGNOSEDGeneticbackgroundCDdefinitionSilentdisease(relatives)Others?DiseaseawarenessDiagnosticfacilitiesGlutenintakeGastrointestinalinfectionsOthers?SlidefromESchoeber22;027 OnsetofceliacdiseaseinfirstyearoflifeChronicdiarrhoeaàFailuretothriveàAbdominaldistensionTypicalsymptoms:HeightWeight22;028 OnsetofceliacdiseaseinfirstyearoflifeBiopsyfromintestinalcellwallliningwithWatson´scapsulePremedicationbutnotgeneralanesthesiaDiagnosis:HeightWeight22;029 AtypicalsymptomsofceliacdiseaseSecondarytomalabsorptionAnaemiaduetoirondeficiencyShortstature,growthfailureBoneloss(osteopenia)RecurrentabdominalpainFlatulenceFattyliver22;0210 AtypicalsymptomsofceliacdiseaseIndependentofmalabsorptionDentalenameldeficiencyAtaxia(unsteadygait)Alopecia(localisedhairloss)InfertilityLaboratoryabnormalities(transaminases)RecurrentaphthousstomatitisEpilepsy(withorwithoutcalcificationsonCTscan)Polyneuropahty(peripheralneuronaldisease)Heartproblems(dilativecardiomyopathy)22;0211 CDandotherdiseasesSkin:DermatitisherpetiformisReducedfertilityIncreasedabortionratesLymfom20-92år,653pat.Migraine:4patientsexperiencedimprovementsinattacksandCTshowednormalizationofbrainuptakeoftracersafterdietGabrielliM.AmJGastroenterol2003;98:625-9.Non-Hodgkinlymphoma(inpersons>20yearsofage):0.92%ofpatientswithlymphomahadCD0.42%ofpatientsincontrolgrouphadCDCatassiC.JAMA2002;287:1413-19.22;0212 Celiacdisease-theclinicalrealityTübingen,Germany:281patients,1.4-25years18(6.4%)werepositiveforEMA,anadditional44(15.7%)forgliadinantibodies18(6.4%)wererecommendedbiopsy12acceptedbiopsy8hadceliacdisease3hadabdominalsymptoms,2/3betterwithdiet3hadirondeficiencyanemia,allbetterwithdietAllhadnormalheightandweight,butforthosecomplyingwithdiettherewasanincreaseinheightHbA1cimprovedfrom8%to7.3%(p=0.05)Sanchez-AlbisuaI.DiabetMed2005;22:1079-82..22;0213 Celiacdisease-theclinicalrealityMulticenter,Italy:4332patients,1.4-25years292(6.8%)werebiopsyconfirmedCDHigherriskingirls(oddsratio~2)In11%,CDwasdiagnosedbeforediabetesCDwas3timesmorecommoninchildren<4yearsage,comparedto>9yearsCeruttiF.DiabetesCare2004;27:1294-8.22;0214 HowdowesuspectCD?Gliadinantibodiesinchildren<2yearsageTGA(transglutaminaseantibodies)isabettertestthanEMA(endomycialantibodies)inpersons>2yearsageALBrutinerenl.FinkelY,HildebrandH.Incitament2003/2;143-145SlidefromESchoeber22;0215 GastroscopicbiopsyinchildrenWedomostbiopsieswiththehelpofagastroscope22;0216 GastroscopicbiopsyNormalintestinallining(mucosa)CeliacdiseaseLowerstomachsphincter(pylorus)Gastro-scopeGulletStmallintestine17 Ahealthymucosawithvilli(“fingers”)DCCTàThepurposeofthevilliistoincreasetheabsorptionareaoftheintestinalmucosato~200squaremeters(~250squareyards)22;0218 FlatmucosafrompatientwithceliacdiseaseàWhenthevilliaredestroyedbyceliacantibodiestheabsorptionareadecreasesto~2squaremeters(~2squareyards)22;0219 ThemucosaseenthroughamicroscopeNormalCeliacdisease22;0220 Follow-upGluten-freedietAntibodiesALBrutinerenl.FinkelY,HildebrandH.Incitament2003/2;143-145Newbiopsy:<2yearsatdiagnosis:#2after1yearofgluten-freediet#3afterprovocationwithgluten-containingdiet>2yearsatdiagnosis:Nore-biopsyifantibodiesdisappearondietandthepersoniswithoutsymptoms22;0221 HbA1candinsulinrequirementsinchildrenDecreasedinsulinrequirementstheyearbeforediagnosisandslightincreaseinHbA1cafterGFDMohnA.JPGN2001;32:37-40.HbA1cInsulin,U/kg18CD&26controlsSlidefromESchoeber22;0222 HypoglycemiaIncreaseinhypoglycemia6monthsbeforeandupto6monthsafterdiagnosisMohnA.JPGN2001;32:37-40.18CD&26controlsSlidefromESchoeber22;0223 Celiacdisease-whathappensinthelongrun?Cork,Ireland:28-yearfollow-upof50adultswithchildhooddiagnosisofCD(notdiabetes)CDfor22-45yearsDiet:50%fullycompliant18%partiallycompliant32%notadheringtodietMotivation:AvoidanceofsymptomsratherthanavoidanceofcomplicationsIrondeficiency:86%ofwomen,21%ofmalesBonemineraldensity:Normalin68%2.6%osteoporosisQualityoflifescoreswerenormalSanchez-AlbisuaI.DiabetMed2005;22:1079-82..22;0224 Long-termhealthrisksinuntreatedCDPersonswithosteoporosis(andnootherdisease)havemoreCDthaninthegeneralpopulation.Lindh,EJ.Intern.Med.1992;231:403ReducedbonemineralizationinasymptomaticCDpatients.Mazure,RAm.J.Gastroenterol1994;89:2130Bonedensityandmetabolismnormalafterlong-termGFDinyoungpersonswithCD.Mora,SAm.J.Gastroenterol.1999;94:389ALBrutinerenl.FinkelY,HildebrandH.Incitament2003/2;143-145Normalmortalityinchildren,twofoldincreaseinoverallmortalityinadults.Logan,RFAGastroenterology1989;97:265.Only30%ofchildrenandadolescentscompliedwithastrictgluten-freediet,butgrowthparameterswereunaffectedbydietarycompliance.WestmanE.JPEM1999;12:433-42.22;0225 CancerrisksinuntreatedCDTheriskofdevelopingcancerisnotincreasedwhencomparedwiththegeneralpopulationinceliacpatientswhohavetakenaGFDforfiveyearsormore.Holmes,GKT.Gut1989;30:333.TencasesoflymphomawerefoundinSwitzerland,5withmalabsorptionbutnonehaddiabetes.Lang-MuritanoM.PediatricDiabetes2002;3:42-45.Calculatedrisk:1/8,000personswithdiabeteswillgetlymphomaover60years–dothesehaveuntreatedCD?Lang-MuritanoM.PediatricDiabetes2002;3:42-45.22;0226 Happywithoutceliacdiet?Switzerland:Classicalceliacdisease–1/1000à”Asymptomaticdisease”–1/137àAlmost1%ofthepopulationhasceliacdisease??!!SwissMedWeekly2002;132:43-47SlidefromTBattelino22;0227 Riskswiththediet?Higherfat/carbohydrateratioinGFDwhichcanbedifficultforapersonwithdiabetesAmJClinNutr2000;72:76-81.àChangeinbodycompositionwithincreasedbodyfatstoresAmJClinNutr2000;72:76-81.àPoorvitaminstatusin50%ofpatientsonGFDAlimentPharmacolTher2002;16:1333-9.SlidefromTBattelino22;0228 CanCDbetreatedwithdrugs??Indiabetes-pronerats,intestinalproductionofzonulinincreasedatage50days.ThisresultedinadecreasedintestinalbarrierfunctionDiabetesantibodiesappearedafter2-3weeksThiswasfollowedbyhighbloodglucoselevelsandclinicaldiabetesBlockingthezonulinreceptordecreaseddiabetesby70%inspiteofcontinuedhighreleaseofzonulinintotheintestine.àTheratsthatdidnotgetdiabetesproducednodiabetesantibodies.WattsT.PNAS2005;102:2916-21.22;0229 ToscreenornottoscreenforCD?YesMostcasesasymptomaticGFDeliminatesmostsymptomsSeveralhealthrisksifuntreatedIncreasedcancerriskoveralifetimeifuntreatedNoDifficultdietthatmanydonotfollowstrictlyanywayDoesaGFDreallypreventcancer?OurroutinesFirstscreening6-12monthsafterdiagnosisRepeatedevery2-3yearsandiftherearesymptoms22;0230 Celiacdiseaseanddiabetes–openquestionsWhomtoscreen?Whentoscreen?Howoftenandforhowlongtoscreen?Isasecondbiopsynecessary,orcanwerelyonantibodyresults?WhatisthenaturalcourseofpotentialorsilentCD(positiveantibodies,positivebiopsy)?ShallpatientswithlatentorpotentialCD(positiveantibodies,negativefirstbiopsy)haverepeatedbiopsies?HowdoweimproveacceptanceofGFDandcompliancetoGFD?31 尿液蛋白质检查 一、尿液微量白蛋白的测定健康人的尿液白蛋白一般小于20mg/L,大于30mg/L时即提示异常。定义：微量白蛋白是指尿中白蛋白含量超过健康人水平，但常规尿蛋白试验为阴性的低浓度白蛋白。检测方法：染料结合法、放射免疫分析、酶联免疫吸附、免疫比浊分析、胶体金纸片 报告方式：定时留尿法（μg/ml;mg/24h)晨尿法(mg/L)随机留尿法(mg/mmolCr;mg/gCr)国际上以尿白蛋白排泄率>20mg/L或尿总蛋白>30mg/24h作为尿微量白蛋白的临界值。 临床意义：尿微量白蛋白在糖尿病肾病中的应用尿微量白蛋白在心血管疾病中的应用尿微量白蛋白在炎症方面的应用其他 二、Bence-Jonesprotein：实质是免疫球蛋白轻链或其聚合物，单聚体分子量为2.3万。凝溶蛋白：pH4.5~5.5，56℃条件加热出现白色混浊及凝固，100℃煮沸以后混浊消失或明显减退，再冷却时又可重新凝固。蛋白电泳时可在α2至γ球蛋白区带间的某个部位出现M区带。 检测方法：对甲苯磺酸沉淀筛选实验：灵敏度3mg/L热沉淀法验证乙酸纤维素膜电泳或者聚丙烯酰胺凝胶电泳：M带免疫固定电泳：区带电泳分离蛋白后，立即将浸有特异抗L链血清的薄膜条直接放到预计出现异常蛋白带的位置上，使之产生抗原抗体的复合物反应。免疫扩散实验：用特异的L链血清进行免疫扩散实验。临床意义：多发性骨髓瘤、原发性巨球蛋白血症 三、β2-microglobulin性质：一种低分子量的蛋白质（1.18万），是细胞膜上完整组织相溶性抗原HLA的一部分。检测方法：放射免疫分析（RIA）、酶免疫分析（EIA）参考值:血β2-M<3.0mg/L尿β2-M<0.2mg/L临床意义：肾小管疾病、血清β2-M异常增高 四、尿液血红蛋白、肌红蛋白及其代谢产物检查1.hemoglobin正常人血浆中游离血红蛋白与珠蛋白结合，以复合物的形式运转至单核-巨噬细胞系统被代谢，不能从尿液中排出。疾病时尿液中血红蛋白有两个来源：1.发生血管内溶血，超过珠蛋白的结合能力，游离血红蛋白从尿液中排出。2.尿路（尤其是上尿路）出血，红细胞在低渗或者高渗的环境下破坏逸出的血红蛋白。 检测方法：试纸法：利用血红蛋白中亚铁血红素具有类过氧化物酶作用，在邻联甲苯胺等供氢体存在下，使过氧化物还原为水，而邻联甲苯胺被氧化成有色物质。免疫测定方法：利用抗人血红蛋白单克隆抗体临床意义：血管内溶血泌尿道出血 2.myoglobin肌红蛋白是横纹肌、心肌细胞内的一种含亚铁血红素的蛋白质，分子量小，易通过肾小球。测定方法：纸片法：原理与血红蛋白测定类似。肌红蛋白能溶于0.8饱和度的硫酸铵溶液中免疫法：利用单克隆抗体ELISA、 3.hemosiderin当发生血管内溶血时，大部分血红蛋白随尿排出，其中一部分血红蛋白被肾小管上皮细胞再吸收后在肾小管上皮细胞内分解形成血铁黄素，再随细胞脱落至尿中排出。检测方法：Prussian反应，当尿中含有铁血黄素时，其中高铁离子与亚铁氰化钾作用，在酸性环境下，产生蓝色的亚铁氰化钾沉淀。注意事项：1.避免铁污染；2.清晨第一次尿阳性率较高临床意义：血管内溶血、行进性血红蛋白尿。 4.porphyrinδ-氨基酮戊酸、卟胆原尿卟啉粪卟啉原卟啉+Fe血红素卟啉尿是指尿中排出过多的卟啉或者其前体测定方法：酸萃取后，紫外线进行检测临床意义：先天性卟啉病、肝性卟啉病 五、Tamm—HorsfallproteinTH蛋白由Henle袢升支与远曲小管的上皮细胞的高尔基复合体产生，是一种肾特异性蛋白质。是构成管型的一种重要蛋白。检测方法：酶联免疫吸附法、放射免疫法临床意义：协助诊断上尿路疾患有助于泌尿系统结石形成机制的研究。 六、尿液酶测定尿液酶的来源：血液的酶：淀粉酶、溶菌酶肾实质的酶：肾小管刷状缘（γ-GT、AAP、LAP、ALP、α-GLU）、溶菌体（NAG、ACP、β-葡萄糖醛酸苷酶）、胞浆（LDH）及线粒体（AST）尿路及生殖系统的酶：前列腺（ACP、NAG）、精液（LDH、hyaluronicacid）、肿瘤细胞 尿液酶测定时尿液标本的处理方法：尿液通常为弱酸性，且蛋白质浓度较低，不利于尿酶活力的保存，因此必须及时测定和处理。大部分尿酶活性比血浆酶活性低，在测定时适当加大标本用量或延长酶作用时间。尿液中含有较高浓度的低分子物质，如尿素、尿酸、肌酐、硫酸盐、磷酸盐等，他们可能是某些酶的抑制剂，因此必须对尿液标本进行预处理：超滤法、透析法、凝胶过滤法 1.N-乙酰-β-D-氨基葡萄糖苷酶(N-acetyl-β–D-glucosaminidase,NAG）NAG是一种位于溶酶体内的酸性水解酶，存在于所有组织中，以前列腺和肾近球肾小管溶酶体含量最高。临床应用：各种肾脏疾病：急慢性肾功能不全、肾病综合症肾移植排斥反应：早期诊断药物性肾损害：其他系统疾病：糖尿病肾病、高血压肾病 2.α-葡萄糖苷酶（α-glucosdiase,α-GLU）α-GLU主要存在于肾小管上皮细胞刷状缘，在血清中的含量极低，且分子量大（9万），不易通过肾小球，因而尿中的α-GLU主要来自肾小管上皮细胞。测定：用麦芽糖做底物，经α-GLU的水解作用生成葡萄糖，再用葡萄糖氧化酶法测定葡萄糖的生成率。临床意义：肾小管损伤的敏感指标 3.谷氨酰转移酶（γ-glutamyltransferase，γ-GT）γ-GT广泛存在于人体各组织中，以肾、肝、胰等组织含量最高。尿中γ-GT浓度较高，原尿无需预先浓缩。用γ-谷氨酰对硝基苯胺做底物，测定游历的对硝基苯胺量。临床意义：γ-GT常作为药物性肾损害的诊断指标。γ-GT在急性肾炎、肾盂肾炎、肾结石时升高γ-GT在慢性肾衰、肾癌时降低。'