转FasL基因的树突状细胞诱导大鼠肝移植免疫耐受的实验研究

目的 观察转FasL基因的树突状细胞（DC）体内注射诱导大鼠肝移植免疫耐受作用,并研究其机制。方法 用“二袖套法”行受体为Wistar大鼠肝移植36例,并随机分为3组：（1）对照组（n＝12）;（2）环孢霉素治疗组（n=12）;（3）转FasL基因治疗组（n=12）,腹腔注射转FasL基因的树突状细胞。手术后7d分别杀死各组4只大鼠,用原位末端标记法及透射电镜观察移植肝细胞及肝脏内淋巴细胞凋亡,其余大鼠用于观察生存期。结果 对照组大鼠在9－15d迅速死亡,TUNEL及电镜观察发现肝细胞变性坏死明显;而环孢霉素治疗组及转FasL基因治疗组免疫排斥以应轻微,移植后大鼠已存活超过6个月,原位末端标记法及电镜均发现FasL基因治疗组肝脏内浸润淋巴细胞凋亡明显。结论 转FasL基因DC细胞治疗能有效地诱导肝移植免疫耐受,其机制是诱导了肝脏内浸润淋巴细胞凋亡。     

浸润淋巴细胞凋亡诱导大鼠肝移植耐受

目的观察移植术后大鼠肝脏内不同细胞成分的凋亡现象,寻找耐受过程中的关键细胞成分,探讨大鼠肝移植耐受机制。方法分离肝脏间质细胞,流式细胞仪检测移植术后大鼠肝脏内不同细胞成分的凋亡现象。结果BN→LEW组大鼠移植肝脏在术后早期发生急性排斥反应,并且移植物内间质细胞存在大量的凋亡,急性排斥反应评分及细胞凋亡指数逐渐升高,术后7 d达到高峰随后下降,前者术后28 d与术前无明显差异(P>0.05);细胞凋亡指数至术后28 d较术前仍有明显差异,明显高于LEW→LEW组(P<0.05)。移植物内发生凋亡的细胞为来自于受体的浸润T淋巴细胞。结论移植物排斥反应评分下降与移植肝脏内CTL清除有关,来源于受体的浸润T淋巴细胞凋亡导致移植肝脏免疫耐受。     

CTLA4-Ig基因对大鼠肝移植后免疫细胞浸润及细胞凋亡的影响

目的研究腺病毒介导的细胞毒性T淋巴细胞相关抗原4-Ig(cytolyticT-lymphocyteassociatedantigen4-Ig,CTLA4-Ig)基因对大鼠肝移植后移植物中免疫细胞浸润和细胞凋亡的影响。方法将大鼠原位肝移植模型分为排斥对照组、环孢素A(CsA)组和CTLA4-Ig组。分别于术后1,3,5,7,12d,用免疫组织化学法和缺口末端标记技术(TUNEL法)分别测定移植物中CTLA4-Ig基因的表达和巨噬细胞、CD8 T细胞浸润及细胞凋亡,并以病理形态学变化作参照。结果静脉注射重组CTLA4-Ig基因腺病毒7d后,大鼠肝脏CTLA4-Ig稳定表达,在肝移植60d后仍呈阳性;CTLA4-Ig组汇管区巨噬细胞、CD8 T细胞浸润明显较排斥对照组少;细胞凋亡指数在术后3、5和7d明显低于排斥对照组(P<0·01),汇管区巨噬细胞、CD8 T细胞浸润数和凋亡指数与排斥反应分级均显著相关。结论重组CTLA4-Ig基因腺病毒经静脉一次给药后能在大鼠肝脏稳定表达,并通过抑制移植物中免疫细胞浸润及移植物细胞凋亡,抑制移植后急性排斥反应。     

不同途径行Sertoli细胞-肝脏联合移植对肝移植术后急性排斥的影响

目的通过不同途径行Sertoli细胞-肝脏联合移植，探讨Sertoli细胞是否可为移植肝提供免疫保护。方法“2步法”分离培养Sertoli细胞，“二袖套管法”行大鼠原位肝移植并以Wistar→SD组合建立排斥反应模型。通过三种途径进行Sertoli细胞-肝脏联合移植。分别观察术后各组症状、体征、肝功能变化、移植肝病理特征等。采用免疫组化、凋亡等技术检测Sertoli细胞功能及作用，探讨其对肝移植急性排斥的影响。结果肝移植急排模型不干预组14只，1只存活超过14d。Sertoli细胞腹腔注射组、阴茎背静脉注射组和供体移植前门静脉注射组分别有5、8、7只存活超过14d。各干预组存活率与对照组比较：后两组差异有显著性（P〈0．05），腹腔注射组差异不显著（P〉0．05）；各干预组之间存活率差异无显著性（P〉0．05）。供肝病理检查显示各干预组排斥反应较对照组轻。免疫组化及凋亡检测发现：肝移植后14d，Sertoli细胞仍存活并表达FasL，Sertoli细胞周围有淋巴细胞集聚及凋亡的淋巴细胞。结论Sertoli细胞对肝移植急性排斥有抑制作用，对供肝有诱导免疫耐受作用，Sertoli细胞通过Fas／FasL途径诱导淋巴细胞凋亡。     

雷公藤多甙对大鼠原位肝移植急性排斥反应的影响

目的 探讨雷公藤多甙(TⅡ)对大鼠肝移植术后急性排斥反应的抑制作用和机制。方法 用“二袖套法”建立Wistar→SD大鼠原位肝移植模型，分对照组(n＝12)和TⅡ治疗组(n＝13)，移植术后第7d两组各杀死部分大鼠，测肝功能、肝组织病理和脾淋巴细胞IL—2活性，其余大鼠留作观察存活时间。结果术后第7d，TⅡ组肝功能损害和移植肝病理急性排斥反应程度轻于对照组，IL—2活性低于对照组。TⅡ组大鼠术后存活时间比对照组明显延长。结论 TⅡ可明显延长肝移植术后存活时间，减轻急性排斥反应程度。     

大黄素对大鼠移植肝细胞凋亡的作用

目的探讨大黄素对大鼠肝脏移植术后肝细胞凋亡的作用。方法建立大鼠肝移植模型,分为三组:对照组,供受体均为LEW大鼠;移植组;供体为LEW大鼠,受体为BN大鼠;大黄素组,在移植组基础上,移植术后每日以大黄素50mg·kg-1腹腔注射。分别于术后第1,3,5,7天各取6只移植大鼠的肝脏,TUNEL法染色,检测肝脏细胞凋亡。以肝脏细胞凋亡阳性细胞数占总肝脏细胞数的百分比作为肝细胞凋亡指数(AI)。结果移植组肝细胞于术后第1天即已出现凋亡,第3天明显增加,第7天达到高峰。大黄素组各时间点肝细胞凋亡指数明显小于对应的移植组(P<0.01)。结论大黄素对肝移植急性排斥反应中肝细胞凋亡有显著抑制作用。     

细胞毒T淋巴细胞在异种肝移植急性排斥反应中的作用

目的：探讨异种肝移植中细胞毒T淋巴细胞（CTL）参与急性排斥反应的机制。方法：三袖套法建立仓鼠到大鼠原位肝移植模型；免疫组化方法检测同基因组与异种移植组（XT组）移植肝术后CD8和CD4型淋巴细胞浸润及Fas-L，穿孔素的表达情况，并运用原位末端标记法检测移植肝细胞的凋亡情况。结果：XT组移植肝术后第2d汇管区出现淋巴细胞浸润，逐日增多，至术后5－6d达高峰；术后第4d穿孔素及Fas-L开始表达，术后第5－6d达高峰；穿孔素的表达始终高于Fas-L。结论：异种肝移植中T淋巴细胞参与了其免疫排斥反应，通过表达穿孔素或Fas-L使靶细胞坏死或凋亡。     

T细胞疫苗对肝脏移植物内浸润细胞凋亡的影响

目的探讨 T 细胞疫苗对肝脏移植物内浸润细胞凋亡的影响。方法应用近交系 DA大鼠和近交系 Lewis 大鼠作为实验动物。制备 DA 大鼠针对 Lewis 大鼠的特异性 T 细胞疫苗(TCV)。第一组(n=8):以 Lewis 大鼠作为供者,以 DA 大鼠作为受者。第二组(n=8):用 Flt3-L(fms-liketyrosine kinase 3 ligand)治疗供者 Lewis 大鼠,以 DA 大鼠作为受者。第三组(n=8):用 Flt3-L 治疗Lewis 大鼠,用 TCV 免疫受者 DA 大鼠。应用三袖套法进行大鼠原位肝移植,观察肝移植物平均存活时间(MST);于移植后第5天获取肝移植物制作组织切片,HE 染色,光镜观察排斥反应情况。同时分离肝脏移植物非实质细胞(NPC),应用流式细胞仪对移植物浸润细胞(GICs)的凋亡和 CD4~+T细胞和 CD8~+T 细胞进行检测。结果第一组进行单纯移植,平均存活时间(MST)为(17±2.6)d、第二组用 Flt3-L 治疗供者后 MST 下降为(5.7±1.4)d(P<0.01)、第三组是在第二组的基础上用 TCV免疫受体诱导耐受,使 MST 显著延长(15.7±4.2)d(P<0.01);移植物组织切片 HE 染色光镜观察所见:第二组可见明显的排斥病理损伤征象,在第一组和第三组未发现明显的排斥性病理改变;GICs凋亡率第一组为(11.94±3.12)%、第二组为(7.92±2.25)%,和第一批比较显著降低(P<0.05),应用 TCV 免疫的第三组 GICs 凋亡率比第二组显著上升,为(25.99±2.49)%(P<0.01);应用 T 细胞疫苗的第三组和单纯移植的第一组其 CD_4/CD_8显著低于第二组(P<0.01)。结论异品系大鼠肝移植物在没有任何免疫抑制治疗的情况下可以被完全接受,供体抗原特异性 TCV 通过诱导肝脏GICs 凋亡抑制 Flt3-L 诱导的肝移植急性排斥反应,GICs 凋亡在同种移植耐受过程中发挥关键作用。     

大鼠肝移植排斥反应时γ干扰素及白细胞介素10的表达及意义

目的 探讨大鼠肝移植排斥反应时γ干扰素(IFN-γ)及白细胞介素10(IL-10)的表达及意义.方法 采用改良的Kamada"二袖套法"制备大鼠原位肝移植模型,同系移植组供、受者均为SD大鼠;同种异体移植组的供者为Wistar大鼠,受者为SD大鼠;另设假手术组.术后7 d处死动物,观察移植肝脏的组织学变化,检测血清IFN-γ和IL-10的含量,以及移植肝脏内IFN-γ和IL-10 mRNA的表达.结果 同种异体移植组移植肝脏有较多坏死肝细胞,汇管区及中央静脉周围可见以淋巴细胞为主的炎症细胞浸润,胆管上皮细胞可见胞浆空泡变性、核固缩或碎裂,整个肝小叶结构紊乱.同系移植组肝脏组织结构仅有轻度缺血再灌注损伤表现,汇管区有较少炎症细胞浸润,胆管上皮细胞结构和肝小叶结构基本正常.同种异体移植组血清IFN-γ为(386.7±14.4)Pg/ml,明显高于同系移植组的(159.8±16.5)pg/ml(P<0.05);同种异体移植组血清IL-10为(126.3±13.1)pg/ml,明显低于同系移植组的(288.3±17.1)pg/ml(P<0.05).同种异体移植组移植肝组织内IF-γ mRNA表达水平明显高于同系移植组(P<0.05),而IL-10 rnRNA表达水平明显低于同系移植组(P<0.05).结论 大鼠肝移植排斥反应时IFN-γ表达明显升高,IL-10表达明显降低;T_H1/T_H2型细胞因子的动态平衡可能在大鼠肝移植排斥反应中起着重要作用.     

RNA编辑酶ADAR1在大鼠肝移植排斥反应中的变化

目的观察RNA编辑酶ADAR1在大鼠肝移植排斥反应中的表达变化。方法实验分为4组①同基因移植组(n=15),取Wistar大鼠的肝脏原位移植给Wistar大鼠;②异基因移植组(n=15),取SD大鼠的肝脏移植给Wistar大鼠;③异基因移植 FK506治疗组(n=15),取SD大鼠的肝脏移植给Wistar大鼠,术后肌注FK506,2mg/(kg·d);④对照组(n=15),对Wistar大鼠不行肝移植,仅行开、关腹手术。建立大鼠原位肝移植模型,分别于术后第3、5及7d各处死5只大鼠,取脾脏组织,用RT-PCR方法检测ADAR1 mRNA的表达变化。结果移植后各组大鼠肝脏、脾脏病理变化随时间发展而呈进行性变化,异基因移植组病理变化最明显。ADAR1 mRNA表达在异基因移植组的各个时相点明显高于同基因移植组和异基因移植 FK506治疗组(P<0.001),于第5d时最明显。结论在大鼠原位肝移植发生急性排斥反应时,ADAR1增高程度与排斥反应的强度变化趋势一致。FK506可以抑制ADAR1的表达,明显减轻移植肝组织的急性排斥反应。     

Radioimmunoassays of Ethinyl-norgestrienone (R-2323) and medroxyprogesterone acetate (MPA) and their clinical applicability

Summary Radioimmunoassays for 2 synthetic progestins (Ethinyl-norgestrienone, R 2323 and medroxyprogesterone acetate, MPA) are demonstrated. 10 patients aged 31 to 72 years were treated with ethinyl-norgestrienone with different schedules and 3 men suffering from benign prostatic hypertrophy were treated with medroxyprogesterone acetate. Plasma levels of testosterone, LH, FSH were monitored before, during and after treatment.     

Benignes Prostatasyndrom (BPS)

Zusammenfassung Die instrumentellen Verfahren zur Behandlung des benignen Prostatasyndroms (BPS) werden heute im Rahmen eines abgestuften Therapieschemas eingesetzt, oft nach vorangegangener medikamentöser Therapie. Neben der seit Jahrzehnten bewährten Standardmethode, der transurethralen Resektion der Prostata (TURP) und deren z. T. essenziellen Modifikationen (Vaporesektion; bipolare Resektion), gelangen zunehmend alternative operative Verfahren, wie transurethrale Mikrowellentherapie (TUMT), transurethrale Nadelablation der Prostata (TUNA) oder Laservaporisation bzw. -resektion, in den Fokus des Interesses. Unter Zuhilfenahme der aktuellen Datenlage, vorzugsweise aus randomisierten kontrollierten Studien (randomized controlled trials, RCT), wird zu den einzelnen Verfahren kritisch Stellung bezogen. Darüber hinaus wird der Stellenwert der offenen Prostataadenomenukleation dargelegt.     

Evaluation of Effect and Comparison of Superoxidised Solution (Oxum) V/S Povidone Iodine (Betadine)

Wounds expose a patient to serious hazards like wound infection, tissue destruction, disfiguring and disabling scars. Use of superoxidised solution (oxum) in infected wounds, ulcers, diabetic wounds, abcesses, burns reduced morbidity and hospital stay with its early wound healing effect. To evaluate the effect of superoxidised water (Oxum) V/s povidone iodine (Betadine) on similar types of wounds. We retrospectively analysed the records of two hundred patients with different types of wounds who attended Department of Surgery, Guru Nanak Dev Hospital/Govt. Medical College, Amritsar from January 2008 to January 2009. The patients were divided into two groups. Group A where topical management and dressing was done using oxum and group B where topical management and dressing was done using betadine. A standard grading in terms of percentage decrease in wound size, periwound oedema/erythema, pus discharge and percentage increase in granulation, fibrin and epithelisation was noted in various types of wounds in both groups. Oxum treated wounds showed reduction in inflammation and their healing earlier than betadine group. Oxum application was safe having no pain and allergic manifestation.     

肾结石患者尿NAG和尿微量白蛋白动态检测及其意义

目的：探讨肾结石患者手术前后尿酶变化及意义.方法：对167例肾结石患者在行微创经皮肾镜取石术（mPCNL）前1周、63例在mPCNL后1周、33例在mPCNL后1个月分别检测尿N-乙酰-β-D氨基葡萄糖苷酶（NAG）/Cr、mAlB/Cr.结果：与无肾结石对照组相比,mPCNL术前和术后1周的NAG/Cr和mAlB/Cr有统计学意义（P＜0.01）;mPCNL术后1周和术后1个月的NAG/Cr与术前无统计学意义,而mAlB/Cr有统计学意义（P＜0.01）.mPCNL术后1个月与术后1周相比：NAG/Cr有统计学意义（P＜0.05）,而mAlB/Cr无统计学意义.结论：尿NAG、尿微量白蛋白可动态监测肾结石患者早期肾损害.     

强直性脊柱炎慢作用药治疗3年以上随访分析

目的：了解柳氮磺胺吡啶、甲氨蝶呤、雷公藤多甙以及三种药物联合治疗强直性脊柱炎的远期疗效。方法：４６例活动性ＡＳ分别给予柳氮磺胺吡啶、甲氨蝶呤、雷公藤多甙以及三种药物联合治疗３年以上，通过观察晨僵腰痛、实验室及放射学检查以及医师与２全面评价的变化来确定疗效。结果：总临床疗效分别为显效８２．６％，有效１５．２％。有５６．５％患者经单种慢作用药治疗可以控制病情发展，６．５％病例需应用两种以上慢作用药，尤     

Transurethral resection of bladder tumour (TURBT)

The goals of transurethral resection of bladder tumour (TURBT) are to identify and eradicate visualized bladder tumour if technically safe and feasible and to obtain a specimen of satisfactory quality to enable accurate histological diagnosis. In the setting of high grade bladder tumour this generally entails the inclusion of detrusor muscle and assessment for the presence of associated carcinoma in situ (CIS), lymphovascular involvement or any variant form of bladder cancer. This will assist in determining risk stratification and prognostication of the bladder cancer and guides further treatment planning. Conversely, if suboptimal TURBT is performed there will be detrimental consequences on patient outcomes in regards to undergrading or understaging, increased recurrence or progression, and subsequently need for further treatments including more invasive interventions. This review article firstly summarises the key principles and complications of TURBT, as well as significance of re-TURBT. We also discuss a number of modifications and advances in detection technology and resection techniques that have shown to improve perioperative as well as pathological and oncological outcomes of bladder cancer. They include enhanced cystoscopy such as blue light cystoscopy (BLC), narrow band imaging (NBI) and en bloc resection of bladder tumour (ERBT) technique using various types of energy source.     

Expression of p16 in Sinonasal Undifferentiated Carcinoma (SNUC) Without Associated Human Papillomavirus (HPV)

Sinonasal undifferentiated carcinoma (SNUC) is an uncommon and highly aggressive neoplasm of the paranasal sinuses and nasal cavity. Its undifferentiated histologic appearance often requires immunohistochemical studies to distinguish it from other high-grade neoplasms. Due to the rarity of SNUC, its immunohistochemical staining profile has been incompletely characterized, and little work has been done on its expression of the markers for human papillomavirus (HPV). Our objective is to expand our knowledge of its immunophenotype and its association with HPV in order to define markers with mechanistic potential in the disease process, or of possible therapeutic importance. A total of five patients (one woman and four men) with SNUC, ranging in age from 26 to 75 years (mean 56.8 years) were compared to five patients (five men) with poorly differentiated squamous cell carcinoma (PDSCC), ranging in age from 53 to 75 years (mean 62.2 years). PDSCC was chosen as a control, given its well-reported immunohistochemical profile and negativity for HPV markers. The immunohistochemical panel included: CK7, CK19, EMA, NSE, chromogranin, p53, CK5/6, p63, CK14, S100, HMB-45, desmin, muscle specific actin, and CD45. Additionally, tests for p16, EBV, and HPV (subtypes 6, 11 16, 18) were performed. The diagnosis of SNUC was confirmed in all cases by histology and immunohistochemical stains. An interesting finding of strong diffuse positivity for p16 was noted in all SNUC cases, compared to only two of five PDSCC that were positive for p16. HPV DNA was not detected in any SNUC cases or any cases of PDSCC. All SNUC cases demonstrated over expression of p16 in the absence of HPV DNA expression. This may represent residual epithelial p16 staining, which is normally present in the sinonasal tract. Due to the rarity of SNUC, more cases will need to be evaluated to confirm the absence of HPV DNA.     

Relationship of non-LDL-bound apo(a), urinary apo(a) fragments and plasma Lp(a) in patients with impaired renal function.

BACKGROUND: Plasma lipoprotein (a) [Lp(a)] has been shown to be a risk factor for atherosclerosis in numerous studies. However, the catabolism of this lipoprotein is not very clear. We and others have shown that Lp(a) is excreted into urine in the form of fragments. Lp(a) has also been shown to exist in a low-density non-lipoprotein (LDL)-bound form. Since Lp(a) is increased in all forms of kidney disease with reduced excretory kidney function and decreased excretion of apo(a) fragments could be partially responsible for this increase, we investigated the relationship of non-LDL-bound apo(a), urinary apo(a) fragments and plasma Lp(a) in patients with impaired renal function. METHODS: Plasma Lp(a), non-LDL-bound apo(a) and urinary apo(a) fragments were measured in 55 kidney disease patients (28 males and 27 females) and matched controls. RESULTS: Plasma Lp(a) and non-LDL-bound apo(a) were increased in patients, whereas urinary apo(a) was decreased, especially in patients with a creatinine clearance < 70 ml/min. There was a significant correlation between plasma Lp(a) and non-LDL-bound apo(a) in patients and controls. CONCLUSION: We conclude that decreased urinary apo(a) excretion could be one possible mechanism of increased plasma Lp(a) and non-LDL-bound apo(a) in patients with decreased kidney function.     

Diffuse Axonal Injury (DAI) is not Associated with Elevated Intracranial Pressure (ICP)

Summary Objective. Traditionally, intracranial pressure (ICP) monitoring has been utilized in all patients with severe head injury (Glasgow coma score of 3–8). Ventriculostomy placement, however, does carry a 4 to 10 percent complication rate consisting mostly of hematoma and infection. The authors propose that a subgroup of patients presenting with severe head trauma and diffuse axonal injury without associated mass lesion, do not need ICP monitoring. Additionally, the monitoring data from ICP, MAP, and CPP for a comparison severe head injury group, and subgroups of DAI would be presented. Materials and methods. Thirty-six patients sustaining blunt head trauma and fitting our strict clinical and radiographic diagnosis of DAI were enrolled in our study. Inclusion criteria were severe head injury patients who did not regain consciousness after the initial impact, and whose CT scan demonstrated characteristic punctate hemorrhages of <10 mm diameter at the greywhite junction, basal ganglia, corpus callosum, upper brainstem, or a combination of the above. Patients with significant mass lesions and documented anoxia were excluded. Their intracranial pressure (ICP) and cerebral perfusion pressure (CPP) were compared to a control group of 36 consecutive patients with severe non-penetrating non-operative head injury, using the Analysis for Variance method. Results. Eighteen (50.0%), six (16.7%), and twelve (33.3%) patients had types I, II, and III DAI, respectively. The admission Glasgow Coma Score (GCS) was higher for types I and II than for type III DAI. ICP was monitored from 23 to 165 hours, with a mean ICP for 36 patients of 11.70 mmHg (SEM=75) and a range from 4.3 to 17.3 mmHg. Of all ICP recordings, of which 89.7% (2421/2698) were ≤20 mmHg. Average mean arterial pressure (MAP) was 96.08 mmHg (SEM=1.69), and 94.6% (2038/2154) of all MAP readings were greater than 80 mmHg. Average cerebral perfusion pressure (CPP) was 85.16 mmHg (SEM=1.68), and 90.1% (1941/2154) of all CPP readings were greater than 70 mmHg. This is compared to the control group mean ICP, MAP, and CPP of 16.84 mmHg (p=0.000021), 92.80 mmHg (p=0.18), and 76.49 mmHg (p=0.0012). No treatment for sustained elevated ICP>20 mmHg was needed for DAI patients except in two; one with extensive intraventricular and subarachnoid hemorrhage who developed communicating hydrocephalus, and another with ventriculitis requiring intrathecal and intravenous antibiotic treatments. Two complications, one from a catheter tract hematoma, and another with Staph epidermidis ventriculitis, were encountered. All patients, except type III DAI, generally demonstrated marked clinical improvement with time. The outcome, as measured by Glasgow Coma Score (GCS) and Glasgow Outcome Score (GOS) was similarly better with types I and II than type III DAI. Conclusion. The authors conclude that ICP elevation in DAI patients without associated mass lesions is not as prevalent as other severe head injured patients, therefore ICP monitoring may not be as critical. The presence of an ICP monitoring device may contribute to increased morbidity. Of key importance, however, is an accurate clinical history and interpretation of the CT scan.     

Peptide YY (PYY) levels and bone mineral density (BMD) in women with anorexia nervosa

INTRODUCTION: Anorexia nervosa (AN) is a psychiatric illness that results in significant bone loss. Studies examining the neuroendocrine dysregulation that occurs in AN may increase understanding of endocrine systems that regulate bone mass. Peptide YY (PYY) is an anorexigenic peptide derived primarily from the intestine, with actions mediated via activation of Y receptors. We have previously shown that PYY levels are elevated in adolescents with AN. Y2 receptor knockout mice have increased bone mineral density (BMD) and thus PYY may play a role in regulating bone mass. We hypothesized that PYY levels would be inversely associated with BMD in women with AN. METHODS: This was a cross-sectional study performed in a General Clinical Research Center of 12 adult women with AN, (mean+/-SEM) mean age 30.9+/-1.8 years, BMI 17.1+/-0.4 kg/m2, and % ideal body weight 77.5+/-1.7%. PYY concentrations were measured hourly from 20:00 h to 08:00 h. BMD was measured using dual X-ray absorptiometry (DXA). RESULTS: In women with AN, mean overnight PYY levels strongly inversely correlated with BMD at the PA spine (r=-0.77, p=0.003), lateral spine (r=-0.82, p=0.002), total hip (r=-0.75, p=0.005), femoral neck (r=-0.72, p=0.009), total radius (r=-0.72, p=0.009) and 1/3 distal radius (r=-0.81, p=0.002). Body mass index was inversely correlated with PYY level (r=-0.64, p=0.03). Multivariate stepwise regression analysis was performed to determine the contribution of age, duration of AN, BMI, fat-free mass, and PYY to BMD. For PA and lateral spine, PYY was the primary determinant of BMD, accounting for 59% and 67% of the variability, respectively. Fat-free mass and duration of anorexia nervosa were the primary determinants of BMD at other skeletal sites. CONCLUSIONS: In women with anorexia nervosa, an elevated PYY level is strongly associated with diminished BMD, particularly at the spine. Therefore further investigation of the hypothesis that PYY may contribute to the prevalent bone pathology in this disorder is merited.