熊胆粉对二甲基亚硝胺诱发大鼠肝纤维化的抑制作用

目的:探讨熊胆粉对二甲基亚硝胺(dimethylnitrosamine,DMN)诱发大鼠肝纤维化的抑制作用.方法:将30只大鼠随机分为正常组、模型组及熊胆组,每组各10只.用10g/LDMN腹腔注射诱发大鼠肝纤维化模型,用400mg/kg熊胆粉灌胃共4wk,检测血清AST、ALT值和总蛋白(TP)含量.肝组织做HE、直接红染色,观察肝组织的病理变化,并检测肝组织内胶原纤维的面密度.免疫组化采用SP法,利用单克隆抗体ED1和α-SMA观察库普弗细胞(Kupffercell,KC)和肝星状细胞(hepaticsatellitecell,HSC)的数量及分布.结果:熊胆组与模型组比较血清ALT值下降,AST值明显下降(4370.87±1338.60nkat/Lvs5741.15±1000.20nkat/L,P<0.05),TP升高,肝/体质量比增加,胶原纤维的面密度明显下降(6.73±1.31vs9.90±1.93,P<0.01).熊胆组肝组织病理变化较模型组轻,纤维间隔变细、或消失,形成弥漫性肝硬化的少.KC和HSC在增生的纤维组织及间隔内分布,熊胆组两种细胞的数量明显减少.结论:熊胆粉具有较好的抑制DMN诱发大鼠肝纤维化的作用,其机制可能与抑制KC,减少细胞因子的分泌,从而抑制HSC的激活和转化,减少胶原纤维合成和分泌有关.     

清肝活血方对乙醇性肝纤维化大鼠肝星形细胞和肝细胞凋亡的影响

目的:观察酒精性肝纤维化大鼠Hsc和肝细胞的凋亡及中药清肝活血方对细胞凋亡的影响.方法:以乙醇为主制备酒精性肝纤维化大鼠模型,将造模大鼠分为清肝活血方低(4.75g/kg)、中(14.25g/kg)和高剂量组(28.5g/kg),每日进行ig药物干预2wk,并设空白对照组、模型对照组及易善复对照组.比色法检测血清ALT,AST,γ-GT;HE和Masson染色观察肝组织炎症和纤维化程度.TUNEL检测肝细胞凋亡,TUNEL-α-SMA双标记检测HSC凋亡.结果:清肝活血方用药组及易善复组能降低大鼠血清ALT(1213±245,1432±253nkat/Lvs2140±428nkat/L,P均<0.05),AST(1671±400,2123±413vs4454±850nkat/L,P均<0.05),γ-GT水平(4539±1847,5509±2430vs8271±3304nkat/L,P均<0.05),减轻纤维化程度(5.5±2.50,6.30±3.16vs9.00±2.27,P<0.05);诱导活化的HSC凋亡(5.25%±2.48%,3.63%±2.04%vs2.30%±1.24%,P<0.05),减少肝细胞凋亡(0.43%±0.11%,0.60%±0.16%vs1.77%±0.49%,P<0.05).结论:清肝活血方能有效减轻大鼠肝纤维化程度,并减少乙醇引起的肝细胞凋亡,诱导活化的HSC凋亡.     

白屈菜红碱对肝纤维化大鼠肝脏TGF-β1和α-SMA表达的影响

目的:探讨白屈菜红碱对四氯化碳诱导肝纤维化大鼠肝脏组织转化生长因β1(TGF-β1)和α-平滑肌肌动蛋白(α-SMA)表达的影响.方法:用四氯化碳皮下注射, 同时联合营养控制和饮用100 mL/L乙醇复合法制备SD大鼠肝纤维化模型, 在实验第4周末, 肝纤维化模型建立(2期肝纤维化形成), 然后用低、中、高剂量白屈菜红碱(0.2、0.6、2.0 g/L)治疗, 同时实验设立病理模型组、空白对照和阳性对照(INF-γ)组. 给药8 wk后, 采用免疫组织化学检测各组大鼠肝脏组织TGF-β1和α-SMA的表达.结果:各剂量白屈菜红碱组肝脏TGF-β1和α-SMA表达明显低于病理模型组(TGF-β1:6.08±2.35, 4.31±2.10, 4.7±1.70 vs 9.33±3.08; α-SMA:3.75±1.76, 3.23±1.42, 3.20±1.17 vs 6.67±2.29, 均P <0.01), 而与INF-γ组比较无明显差异(4.23±2.24, 3.38±1.39, 均P >0.05).结论:白屈菜红碱能降低四氯化碳诱导的肝纤维化大鼠模型肝脏组织TGF-β1和α-SMA.     

瘦素在肝纤维化组织中的表达及其与肝星状细胞活化的关系

目的:探讨瘦素(leptin)在肝纤维化组织中的表达及其与肝纤维化过程中转化生长因子(TGF-β1)以及α平滑肌肌动蛋白(α-SMA)表达的相关性,了解leptin与肝星状细胞(HSC)活化的关系.方法:健康 SD大鼠40R,随机分成正常对照组和CCl4诱导的肝纤维化模型组.于造模2、4、6 wk末分批处死动物,分别采用RT-PCR和Western blot、免疫组织化学方法联合检测leptin、TGF-α1及α-SMA在肝纤维化组织中的表达.结果:正常对照组肝脏组织中leptin、TGF-β1、α-SMA均有微量表达;CCl4注射2wk后,leptin、TGF-β1、α-SMA表达开始增强,2、4、6 wk肝组织中的表达强度呈明显递增趋势(P<0.05).leptin与TGF-β1和α-SMA表达均呈显著相关性(r=0.668,0.570,均P<0.05).结论:leptin的阳性表达随着肝纤维化程度的加重而增强.在肝纤维化过程中leptin可能参与了HSC活化、增殖以及ECM的合成.     

牛磺熊去氧胆酸抑制四氯化碳诱导的大鼠肝纤维化

目的:探讨牛磺熊去氧胆酸(TUDCA)对四氯化碳(CCl4)诱发大鼠肝纤维化的抑制作用.方法:健康6周龄♂SD大鼠75只,随机分为空白对照组、模型对照组、TUDCA低剂量组、TUDCA高剂量组、己酮可可碱(PTX)阳性对照组,每组15只.用40%的CCl4油溶液,大鼠背部皮下注射3 mL/kg(首次5 mL/kg)造大鼠肝纤维化模型.各组给予相应浓度干预药物溶液灌胃8 wk,检测血清纤维化指标HA、LN、Ⅳ-C:胶原纤维染色(Masson三色染色)观察各组胶原纤维面积比变化;免疫组织化学SP法观察TGF-β1及α-SMA在大鼠肝组织中的表达及分布变化.结果:8 wk后,TUDCA及PTX干预组与模型组相比,血清HA、LN、Ⅳ-C有明显降低(146.33±35.13,162.2±24.80,137.14±22.24 vs 252.83±51.94;77.20±11.84,66.80±16.78,82.00±10.74 vs 108.00±30.00;14.14±2.59,12.60±3.17,10.09±2.22 vs 25.08±5.93,均P<0.05);肝组织纤维间隔变细或消失,形成弥漫性肝硬化结节减少,胶原面积比降低(P<0.05);免疫组织化学结果显示,TUDCA及PTX干预组与模型组相比,TGF-β1及α-SMA阳性表达减少,图像软件半定量分析结果显示差异有显著性(P<0.05).而TUDCA低剂量组与高剂量组及PTX组三者之间结果差异无显著性.结论:TUDCA对CCl4诱发的大鼠肝纤维化有拮抗作用,主要是通过减少TGF-β1合成,抑制HSC细胞活化,降低细胞外基质合成.延缓肝纤维化进程.     

四氯化碳诱导的大鼠肝纤维化肝组织中SHP2表达与在体肝星状细胞活化及增殖的关系

目的 探讨四氯化碳诱导的大鼠肝纤维化肝组织及在体肝星状细胞(HSC)的含SH2结构域的蛋白酪氨酸磷酸酶2(SHP2)表达变化与在体HSC活化及增殖的关系。方法 随机将50只健康雄性SD大鼠分为对照组(10只)、模型组(40只),采用腹腔注射四氯化碳法构建大鼠肝纤维化模型，Masson三色及HE染色检测大鼠肝组织的病理组织学变化，免疫组织化学染色检测大鼠肝组织的α-平滑肌肌动蛋白(α-SMA)及SHP2表达，SHP2与α-SMA免疫荧光双标记检测大鼠肝组织中活化HSC的SHP2表达。结果 与对照组大鼠肝组织的α-SMA阳性表达积分光密度值(IOD)(0.09±0.01)相比，造模不同时间(2周、4周、6周、8周)大鼠纤维化肝组织的α-SMA阳性表达IOD (0.13±0.01、0.18±0.01、0.24±0.02、0.28±0.02)显著增加(P<0.05),并随着造模时间延长逐渐升高(P<0.05),即在体HSC的活化及增殖逐渐加快(α-SMA是HSC的活化标志)。造模不同时间(2周、4周、6周、8周)大鼠纤维化肝组织的SHP2阳性表达IOD (0.23±0.01、0.2...     

化学合成经修饰抗TIMP-2小干扰RNA对CCl4诱导肝纤维化动物模型的影响

目的:研究化学合成经修饰抗金属蛋白酶组织抑制剂-2(TIMP-2)小干扰RNA(siRNA)对CCl4诱导的大鼠肝纤维化的影响及其作用机制.方法:SD大鼠42只随机平均分成7组:正常组、阴性对照组、假手术组、模型组,治疗组(分3组,分别用0.05、0.1、0.2mg/kgsiRNA尾静脉注射).以400mL/LCCl4(3μL/g)sc诱导大鼠肝纤维化.8wk后所有动物取肝组织标本,测门静脉血压(PVP)并经腹主动脉取血.常规HE染色和VanGieson(VG)胶原染色,检测血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、透明质酸(HA)、层粘连蛋白(LN)、Ⅲ型前胶原(PCⅢ)、Ⅳ型胶原(CIV)和羟脯氨酸(Hyp).应用荧光实时定量PCR法检测TIMP-2、Ⅰ型胶原纤维(COLⅠ)、Ⅲ型胶原纤维(COLⅢ)和α-平滑肌肌动蛋白(α-SMA)mRNA的表达.应用Westernblot或明胶酶谱法检测TIMP-2、α-SMA和MMP-2蛋白的表达.结果:各治疗组在应用抗TIMP-2siRNA治疗后组织学病变减轻,PVP较模型组降低(2.2±0.1,1.9±0.1,1.6±0.1kPavs2.7±0.1kPa,P<0.05),血清ALT和AST减少(2089.3±154.5,1869.8±138.0,1422.5±139.7nkat/Lvs2717.2±193.8nkat/L,P<0.05;3634.1±242.7,2739.4±141.3,2286.6±145.5nkat/Lvs4067.5±251.5nkat/L,P<0.05),反映肝纤维化指标的HA,LN,PCⅢ,CIV和Hyp均显著低于模型组(176.0±10.2,160.6±9.3,109.9±9.4μg/Lvs206.3±17.0μg/L,P<0.05;93.1±8.2,71.4±7.5,55.9±7.3μg/Lvs116.6±10.8μg/L,P<0.05;71.2±6.1,64.1±5.1,53.6±4.3μg/Lvs91.2±8.9μg/L,P<0.05;64.3±5.4,50.7±5.8,41.6±4.4μg/Lvs80.3±6.8μg/L,P<0.05;328.7±17.6,279.7±16.3,230.4±16.1μg/gvs380.7±20.6μg/g,P<0.05).各治疗组TIMP-2,COLⅠ,COLⅢ和α-SMAmRNA的表达较模型组明显减少(7.53±0.83,5.04±0.75,1.30±0.49vs23.23±2.14,P<0.05;33.38±2.85,22.80±2.48,11.45±1.27vs43.18±3.32,P<0.05;19.23±1.95,13.21±1.35,10.11±1.09vs25.90±2.23,P<0.05;23.76±2.06,15.33±1.25,10.53±1.02vs34.85±3.16,P<0.05),且TIMP-2,MMP-2和α-SMA蛋白的表达也相应减少(23.27±3.06,14.13±1.86,9.16±1.33vs44.83±5.45,P<0.05;23.80±2.14,15.58±1.52,9.52±0.93vs39.90±3.23,P<0.05;24.58±2.59,19.29±2.31,13.40±1.98vs57.19±7.07,P<0.05).结论:化学合成经修饰抗TIMP-2siRNA能显著降低TIMP-2的表达,促进细胞外基质的降解,抑制肝星状细胞的活化.     

β-榄香烯对实验性肝纤维化大鼠TGF-β1、α-SMA、Col-Ⅰ表达的影响

目的:观察β-榄香烯对四氯化碳肝纤维化大鼠TGF-β_1、α-SMA、Col-Ⅰ表达的影响方法:采用CCl_4皮下注射诱导Wistar♂大鼠肝纤维化模型,用β-榄香烯0.1 mL/100g剂量每天腹腔注射8 wk后,用苏木精-伊红染色(HE)和胶原纤维(Masson)染色观察大鼠肝脏病理变化,酶动力法检测肝功能.SP免疫组化法检测肝组织中α-肌动蛋白(α-SMA)、转化生长因子β_1(TGF-β_1)、Ⅰ型胶原(Col-Ⅰ)表达的变化,样本碱水解法检测肝组织中羟脯氨酸(HYP)的含量.结果:8 wk后,正常组、模型组、对照组及治疗组肝组织胶原纤维面积百分比分别为1.22%±0.24%,7.47%±0.81%,5.57%±0.78%,4.33%±0.48%,治疗组与模型组、对照组相比均有显著差异(P<0.01),并且治疗组肝组织纤维化程度分级较模型组逐渐好转,胶原纤维所占面积显著缩小;在肝组织中测得的Col-Ⅰ阳性面积比分别为3.022%±0.553%,9.998%±1.431%,7.554%±0.914%,4.587%±1.008%,治疗组与模型组、对照组相比均有显著差异(P<0.01).α-SMA和TGF-β_1在治疗组和模型组肝组织中的表达也有显著差异(3.172%±0.542% vs 5.605%±1.315%,P<0.01;2.868%±0.554% vs 5.653%±0.9%,P<0.01).结论:β-榄香烯对四氯化碳肝纤维化大鼠具有拮抗作用,主要是通过抑制肝星状细胞激活,降低TGF-β_1,α-SMA在肝组织中的表达,减少细胞外基质在肝脏中的沉积,从而延缓肝纤维化的进程.     

uPA基因转染骨髓源性肝干细胞移植对肝纤维化大鼠HSC活化的影响

目的:探讨尿激酶型纤溶酶原激活物(uPA)基因修饰骨髓源性肝干细胞(BDLSC)移植对CCl4诱导的大鼠肝星状细胞(HSC)激活的影响.方法:大鼠sc 400mL/LCCl4造模.36只大鼠随机分为4组:(1)正常组:sc等量橄榄油;(2)模型组;(3)BDLSC组;(4)BDLSC-uPA组,每组9只.各组大鼠于第8周处死,留取血清及肝组织.观察大鼠肝功能的变化;采用免疫组织化学法和Western blot法检测大鼠肝组织仅α-平滑肌肌动蛋(α-SMA)蛋白表达变化.结果:与模型组和BDLSC组相比.BDLSCuPA组大鼠血清丙氨酸转氨酶(ALT)和总胆红素(TBIL)水平均有不同程度的降低(86.5±9.7 vs 187.1±14.8,113.5±15.7:11.5±2.1 vs 26.3±3.7,17.94±2.8,均P<0.01),血清透明质酸(HA)和Ⅲ型前胶原(PCⅢ)水平明显降低(47.4±10.1vs148.5±22.4,97.6±14.4:18.9±4.4 vs 39.0±6.1,28.2±4.1,均P<0.01); 肝组织α-SMA表达显著下调(0.0174 0.0048 vs 0.3404 0.0662,0.1080 0.0408,均P<0.01).结论:uPA基因修饰BDLSC移植能有效抑制CCl4诱导的大鼠肝纤维化,改善纤维化大鼠的肝功能,且抑制HSC的活化可能是其抑制肝纤维化的主要机制之一.     

扶正化瘀方对肝纤维化模型大鼠肝组织纤维化及肝星状细胞的影响

目的 评价扶正化瘀方对肝纤维化模型大鼠肝组织纤维化及活化肝星状细胞(HSC)的影响. 方法 64只雄性SD大鼠随机分为正常对照组、四氯化碳(CCl4)肝纤维化模型组、药物干预低剂量组和药物干预高剂量组.除正常组外,所有大鼠用CCl4复合法制备大鼠肝纤维化模型；在造模同时,药物干预组给予扶正化瘀方灌胃,1次/d,6次/周,共6周(低剂量组按0.75g/kg,高剂量组1.5 g/kg);分别在实验的第2、4、6周处死正常组、模型组及药物干预低、高剂量组大鼠各4只,收集大鼠血清及肝组织标本,测定大鼠血清ALT、AST、总胆红素(TBil);组织标本常规石蜡包埋、切片、HE染色及Masson三重染色,采用计算机图像分析测定大鼠肝组织纤维化面积比例；测定α-平滑肌肌动蛋白(α-SMA)的积分吸光度值.组间数据比较用完全随机设计的单因素方差分析.结果 2周末正常对照组、模型对照组、药物干预低、高剂量组ALT分别为(24.68±1.50) U/L、(85.33±5.68)U/L、(56.49±4.85) U/L、(36.94±5.23)U/L,4组比较,F值为98.11,差异有统计学意义；4组的AST值分别为(37.69±3.35)U/L、(112.34±7.02) U/L、(82.89±5.32) U/L、(61.39±6.06)U/L,4组比较,F值为96.31,差异有统计学意义；4组的TBil值分别为(6.70±1.10) U/L、(14.12±0.68) U/L、(10.85±0.64) U/L、(7.78±0.69) U/L,4组比较,F值为51.67,差异有统计学意义.4周末4组ALT、AST、TBil比较,F值分别为111.24、72.11、101.20,P值均＜0.05,差异均有统计学意义；6周末4组ALT、AST、TBil比较,F值分别为154.16、190.80、158.91,P值均＜0.05,差异均有统计学意义.与正常组比较,2、4、6周末模型组、扶正化瘀高、低剂量各组ALT、AST、TBil的水平均有不同程度的升高；与模型组比较,药物干预各组ALT、AST、TBil数值均有不同程度下降,其中以扶正化瘀方高剂量组改善最为显著.与正常组比较,模型组、药物干预低、高剂量组肝组织纤维化面积比例明显升高,2周末正常组、模型组、药物干预低、高剂量组肝组织纤维化面积比例分别为5.23％±0.10％、11.93％±1.78％、9.33％±1.09％、8.26％±0.77％,4组比较,F=18.68,P＜0.01；4周末、6周末正常组、模型组、药物干预低、高剂量组肝组织纤维化面积比较,F值分别为49.95、82.44,P值均＜0.01,差异均有统计学意义.随着造模时间的延长,α-SMA表达亦较正常对照组均有升高,药物干预低、高剂量组大鼠肝组织α-SMA的表达与正常组和模型组比较,均明显下调,且药物干预高剂量组α-SMA表达下调显著.结论 扶正化瘀方具有抗肝纤维化的作用,且可减少α-SMA的表达,其抗肝纤维化机制可能是通过促进活化HSC的凋亡,减少活化HSC的数量.     

The immunoneuroendocrine role of melatonin

Abstract: A tight, physiological link between the pineal gland and the immune system is emerging from a series of experimental studies. This link might reflect the evolutionary connection between self-recognition and reproduction. Pinealectomy or other experimental methods which inhibit melatonin synthesis and secretion induce a state of immunodepression which is counteracted by melatonin. In general, melatonin seems to have an immunoenhancing effect that is particularly apparent in immunodepressive states. The negative effect of acute stress or immunosuppressive pharmacological treatments on various immune parameters are counteracted by melatonin. It seems important to note that one of the main targets of melatonin is the thymus, i.e., the central organ of the immune system. The clinical use of melatonin as an immunotherapeutic agent seems promising in primary and secondary immunodeficiencies as well as in cancer immunotherapy. The immunoenhancing action of melatonin seems to be mediated by T-helper cell-derived opioid peptides as well as by lymphokines and, perhaps, by pituitary hormones. Melatonin-induced-immuno-opioids (MHO) and lymphokines imply the presence of specific binding sites or melatonin receptors on cells of the immune system. On the other hand, lymphokines such as -γ-interferon and interleukin-2 as well as thymic hormones can modulate the synthesis of melatonin in the pineal gland. The pineal gland might thus be viewed as the crux of a sophisticated immunoneuroendocrine network which functions as an unconscious, diffuse sensory organ.     

Changes in connexin43, the gap junction protein of astrocytes, during development of the rat pineal gland

Abstract: The abundance of gap junctions between rat pineal astrocytes formed by connexin43 (Cx43) was studied during development. Levels and distribution of Cx43 were measured by immunoblotting and indirect immunofluorescence, respectively. The amount of Cx43 in cells located within the gland was low until about the 7th postnatal day and increased to adult values between the 14th and 21st days postpartum. Although astrocytes, recognized by their vimentin immunoreactivity, were scarce before birth, they were abundant by the 7th postnatal day suggesting that the low levels of Cx43 found at this age corresponded to a low expression of this protein. Localization of the immunoreactivity to Cx43 and vimentin showed a close correlation, indicating that mature or immature pineal astrocytes form gap junctions made of Cx43. Since Cx43 levels attained their adult values at about the time the innervation and the functional state of the gland reached maturity (2–3 weeks after birth), it is proposed that astrocyte gap junctions are involved in the function of the adult rat pineal gland.     

Response of rat pineal melatonin to calcium, magnesium, and lithium is circadian stage dependent

Abstract: Herein we documented the response of pineal melatonin production to electrolytes known to be effective on pineal function in view of a possible circadian stage dependence. We studied the release of melatonin by perifused rat pineal glands at 2 different circadian stages corresponding to the middle of the light and dark periods, i.e., respectively, 7 and 19 HALO (Hours After Light Onset, L:D = 12:12). The initial efflux rates were, as expected, much higher in the perifusates of glands removed from rats sacrificed during the dark phase than of those removed during the light phase. After 3 hr of perifusion, melatonin release reached similar levels which were found constant up to the 8th hr of perifusion, whatever the circadian stage. Perifusion of the glands with physiological concentrations for the rat of calcium (5.2 mmol/1) and magnesium (1.34 mmol/1) resulted in a stimulatory effect on the pineal glands removed from rats sacrificed in the middle of the dark period (19 HALO), whereas no effects were observed on the pineal glands removed from rats sacrificed during the light (7 HALO). Lithium (0.28 and 0.55 mmol/1) was ineffective on melatonin release in pineal glands removed 7 and 19 HALO. Our results show differences in the initial efflux rates of melatonin and in the response of perifused pineal glands to calcium and magnesium according to the circadian stage.     

Conservative management of perforated duodenal diverticulum： A case report and review of the literature

Duodenal diverticula are a relatively common condition. They are asymptomatic, unless they become complicated, with perforation being the rarest but most severe complication. Surgical treatment is the most frequently performed approach. We report the case of a patient with a perforated duodenal diverticulum, which was diagnosed early and treated conservatively with antibiotics and percutaneous drainage of secondary retroperitoneal abscesses. We suggest this method could be an acceptable option for the management of similar cases, provided that the patient is in good general condition and without septic signs.     

Presence of immunoreactive growth hormone and prolactin in the ovine pineal gland

Abstract: The use of antisera raised against bovine growth hormone (GH) and ovine prolactin (PRL) enabled the detection of related immunoreactive (ir) sequences of proteins in ovine pineal tissue. The isolation of PRL-like ir-material was accomplished using a 0.25 M ammonium sulphate (pH 5.5) extraction followed by ethanol precipitation, whereas the resulting 2.0 M ammonium sulphate (pH 7.0) precipitate contained a GH-like immunoreactivity. Gel chromatography of the GH-like immunoreactivity (Sephadex G-100) indicated the presence of several GH-like fragments ranging in the M_r range of 7,000 to 55,000. Analyses of the PRL-like ir-material found in pineal tissue on HPLC using a TSK 545-DEAE column led to the resolution into a single peak of immunoreactivity. A single peak of activity was also observed following chromatofocusing and hydrophobic interaction chromatography of the ir-peak from the TSK 545-DEAE column. The PRL-like ir-material inhibited the binding of [¹²⁵I]ovine PRL-S14 to anti-ovine PRL antibodies without showing an affinity for binding to anti-rat PRL or anti-bovine GH antibodies. Scatchard analysis of the binding of pineal PRL-like ir-material and pituitary ovine PRL-S14 to liver membranes from day-20 pregnant rats revealed similar affinity constants (K_a of 4.7 ± 0.2 × 10⁹ M^-1). In addition, the replication of Nb 2 Node rat lymphoma cells was stimulated by pineal PRL-like ir-material, an effect known to be specific for lactogenic hormones. The pineal PRL-like immunoreactivity appeared on sodium dodecyl sulfate polyacrylamide gels as a single major band of M_r 24,000. The functional status of PRL-and GH-like ir-material in the ovine pineal remains to be determined, but evidence is presented that the overall protein synthesis rate of the rat pineal responded to circulating concentrations of PRL.     

Microbiology of human immunodeficiency virus anorectal disease

PURPOSE: Individuals who are seropositive for the human immunodeficiency virus are at high risk for opportunistic infection and anorectal disorders. Little prospective information is available regarding anorectal pathogens in these patients. METHODS: One hundred sixty-three HIV-seropositive patients presented to the colorectal clinic between 1989 and 1992. Forty-seven (29 percent) patients were thought to have an infectious process and were prospectively studied using a standardized multiculture protocol. RESULTS: Mean age was 33 (range, 19–59) years. All were male; high-risk behavior accounted for 87 percent of HIV transmissions. Presenting complaints included anorectal pain (79 percent), pus per anum (28 percent), and blood per anum (26 percent). Examination revealed perianal tenderness (60 percent), condyloma (38 percent), perianal ulcers (38 percent), and anal fissures (34 percent). Sixty-six sets of cultures were performed; 28 patients had one set, 15 had two sets, and 4 had three sets. Thirty-two of these 47 patients (68 percent) had positive cultures including herpes (50 percent), cytomegalovirus (25 percent),Neisseria gonorrhoeae (16 percent), chlamydia (16 percent), acidfast bacilli (2 percent), and others (9 percent). Six of 32 patients with positive cultures had more than one organism cultured. Sixteen (50 percent) patients with positive cultures were treated medically, 8 (25 percent) were treated surgically and 8 (25 percent) were treated with both modalities. Sixty-one procedures were performed on 17 patients for condylomata. Eighteen patients had 20 procedures for abscesses, 50 percent of whom had positive cultures for other than common bowel flora; all improved. Fourteen patients underwent 33 procedures for perianal fistulas.Mycobacterium fortuitum was cultured from one patient who required 13 procedures for abscesses and fistulas. Forty-five (96 percent) patients were followed for an average of 12.5 months ±2.9 SEM (range, 1–94 months). Symptoms were improved or resolved in 22 of 32 (69 percent) patients with positive cultures and in 11 of 13 (84 percent) with negative cultures. CONCLUSIONS: Specific pathogens may often be identified in human immunodeficiency virus-seropositive patients with anorectal disorders if aggressively sought. Although patients without specific pathogens identified may be expected to improve with planned empiric treatment, positive identification allows more directed therapy.