SIRT1信号通路在白藜芦醇保护脑缺血再灌注损伤中的作用机制

目的探讨白藜芦醇(Res)对大脑缺血再灌注损伤后大鼠神经元凋亡的影响及其作用机制。方法采用线栓法制作短暂性大脑中动脉栓塞(MCAO)模型。将60只SD大鼠随机分为假手术组(Sham组)、脑缺血再灌注模型组(MCAO组)、白藜芦醇低剂量(10 mg/kg)组(Res 10组)、白藜芦醇高剂量(30 mg/kg)组(Res 30组)。栓塞缺血2 h、再灌注24 h后对各组大鼠进行神经功能损伤评分、脑组织含水量及脑梗死体积评估,TUNEL染色检测细胞凋亡,同时测定缺血再灌注损伤缺血测脑组织中SIRT1、Bax、Caspase-3 mRNA表达水平。结果脑缺血再灌注后24 h,MCAO组脑梗死体积大于Sham组(P0.01),神经功能损伤评分、脑组织含水量、TUNEL(+)细胞数及Bax mRNA、Caspase-3 mRNA表达量均明显高于Sham组(P0.01),而SIRT1 mRNA表达量较Sham组明显降低(P0.01)。与MCAO组比较,Res 10组、Res 30组脑梗死体积明显缩小(P0.01),神经功能损伤评分、脑组织含水量、TUNEL(+)细胞数以及脑组织中Bax mRNA、Caspase-3 mRNA表达量明显降低(P0.01),SIRT1 mRNA表达明显增加(P0.01)。结论白藜芦醇可通过减轻缺血脑组织神经元凋亡对大鼠脑缺血再灌注损伤发挥神经保护作用,其可能通过激活SIRT1信号通路从而抑制或逆转脑缺血再灌注神经损伤的发生。     

参芎注射液对脑缺血再灌注大鼠炎症因子变化的影响

目的观察脑缺血再灌注(I/R)大鼠脑组织核因子-κB(NF-κB)、肿瘤坏死因子-α(TNF-α)、细胞间粘附分子-1(ICAM-1)表达及血清白细胞介素(IL)-1β、IL-6、IL-10质量浓度的变化,并探讨参芎注射液对其影响。方法2006年4月至7月间于苏州大学附属第二医院将54只健康雄性大鼠随机分为生理盐水对照组、川芎嗪组和参芎组。采用线栓法制作大脑中动脉I/R模型,缺血1h时回抽栓线实现再灌注,造模成功后,于再灌注6h、12h及24h3个时间点断头取脑及采血;采用免疫组化法标记脑组织NF-κB、TNF-α及ICAM-1表达;用酶联免疫吸附试验(ELISA)法检测血清IL-1β、IL-6及IL-10质量浓度。结果各组脑组织TNF-α、ICAM-1均随再灌注时间延长而表达增强,但NF-κB于再灌注12h达高峰;与对照组相比,参芎组NF-κB、TNF-α及ICAM-1表达明显减弱(P均<0.05);参芎可降低IL-1β的质量浓度,促使IL-6的峰值提前,提高IL-10的质量浓度(P<0.05或P<0.01)。结论参芎注射液抑制脑I/R炎症损伤的作用优于川芎嗪。     

不同剂量右美托咪定对大鼠脑缺血再灌注损伤脑组织TNF-α、IL-1β及ICAM-1表达的影响

目的探讨不同剂量右美托咪定(DEX)对大鼠脑缺血再灌注损伤脑组织肿瘤坏死因子(TNF)-α、白细胞介素(IL)-1β及细胞间黏附分子(ICAM)-1表达的影响。方法按照随机数字表法将60只健康SD大鼠分为假手术组(Sham组)、缺血再灌注组(I/R组)、DEX组(低剂量DEX组、中剂量DEX组和高剂量DEX组),每组各12只。采用栓线法制备大鼠大脑中动脉阻塞缺血再灌注模型,造模结束后Sham组和I/R组大鼠持续静脉泵入生理盐水2 h,速度为2 ml/h,低剂量DEX组、中剂量DEX组和高剂量DEX组大鼠分别静脉输注0.05、0.50、5.00μg·kg~(-1)·min~(-1)DEX,持续静脉泵注2 h。造模结束后,评估各组大鼠神经功能缺损程度和梗死区域面积,采用酶联免疫吸附法(ELISA)检测血清中TNF-α、IL-1β及ICAM-1的表达水平,同时应用免疫组化法检测各组大鼠脑组织中TNF-α、IL-1β及ICAM-1的表达水平。结果造模大鼠均出现了一定程度的神经功能缺损和梗死面积,其他各组大鼠神经功能评分及梗死面积均明显高于Sham组,同时高、中、低剂量DEX组大鼠神经功能评分及梗死面积均显著低于I/R组(P<0.05);与Sham组相比,其他各组大鼠血清和脑组织中TNF-α、IL-1β及ICAM-1表达水平均明显升高(P<0.05);与I/R组相比,高、中、低剂量DEX组大鼠血清和脑组织中TNF-α、IL-1β及ICAM-1表达水平显著降低(P<0.05),但是不同剂量DEX组大鼠神经功能评分、梗死面积及血清和脑组织中各检测指标水平之间的差异无统计学意义(P>0.05)。结论 DEX可以明显减少缺血再灌注损伤大鼠神经功能缺损程度和梗死面积,并且能够通过抑制血清及脑组织中炎症因子的表达,从而发挥脑保护作用,同时无显著的剂量相关性。     

银杏二萜内酯对大鼠脑缺血再灌注后氧化应激和炎症反应抑制作用的研究

目的研究银杏二萜内酯葡胺注射液(DGMI)对大鼠局灶性脑缺血再灌注(I/R)后氧化应激和炎症反应的抑制作用,并探讨其可能的作用机制。方法设假手术组、I/R组和DGMI低、中、高剂量组,各28只;采用改良线栓法复制局灶性脑I/R大鼠模型,术后第2天开始腹腔注射给药,疗程7 d。盲法对神经功能损伤进行评分,失重法计算脑组织含水量,TTC染色法计算脑组织梗死体积百分比;生化分析脑组织氧化酶活性和丙二醛(MDA)含量;测定脑组织中一氧化氮(NO)含量和诱导型一氧化氮合酶(inducible NOS, iNOS)活性;通过HE染色、TUNEL法分别进行脑组织病理学检查及神经元凋亡状况观察;Western blotting法检测核转录因子-κB(NF-κB)蛋白表达;酶联免疫法测定脑组织炎症细胞因子含量。结果经DGMI中、高剂量治疗7 d能显著降低I/R大鼠神经功能缺损评分,降低脑组织含水量和梗死体积百分比;提高脑组织中抗氧化酶超氧化物歧化酶(SOD)、过氧化氢酶(CAT)活性,并降低MDA含量;改善脑组织形态结构病变和神经元凋亡状况,降低凋亡指数(apoptosis Index, AI),下调NF-κB蛋白表达;降低炎症细胞因子白介素-1β(IL-1β)、白介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)含量;与I/R组比较差异均具有统计学意义(P0.05或P0.01)。结论 DGMI对脑I/R大鼠氧化应激损伤和炎症反应均具有一定的抑制作用。     

小檗碱对大鼠脑缺血再灌注损伤脑组织Bcl-2、Caspase-3表达的影响

目的 探讨小檗碱对大鼠局灶性脑缺血再灌注损伤后神经功能评分及脑梗死体积,以及Bcl--2、Caspase-3表达的影响.方法 线栓法建立大鼠局灶性脑缺血再灌注损伤模型,大鼠随机分为模型组、小檗碱低、高剂量组(50,150 mg·kg-1·d-1)、假手术组(持续给药7 d,每日1次灌胃给药),脑缺血2 h再灌注24 h;分别在再灌注后3和24 h进行神经行为评分;并再灌注24 h后断头取脑.采用连续切片免疫组化技术检测脑组织中Bcl-2、Caspase-3表达的部位及数量.结果 小檗碱组神经功能评分明显低于手术对照组.脑梗死体积较模型组显著缩小.小檗碱组大鼠额顶部皮质Bcl-2、Caspase-3免疫阳性细胞数与模型组相比差异明显(P<0.05);同时小檗碱高剂量组大鼠额顶部皮质Bcl-2、Caspase-3免疫阳性细胞数与低剂量组比较差异显著(P<0.05).结论 小檗碱能明显减轻脑缺血再灌注损伤所造成的行为障碍,缩小梗死体积.可能通过上调皮质Bcl-2的表达、抑制Caspase-3的表达发挥脑保护作用.     

小檗碱对大鼠急性脑梗死的治疗作用及其机制

目的 观察小檗碱对大鼠急性脑梗死的治疗作用，并探讨其作用机制。方法 采用改良线栓法进行急性脑梗死模型制备，将造模成功的48只大鼠随机分为低剂量小檗碱组、高剂量小檗碱组、小檗碱+Wnt/β-连环蛋白（β-catenin）信号通路抑制剂（DKK-1）组、模型组各12只；另取12只大鼠作为假手术组（实验过程中仅暴露动脉血管，不结扎）。低、高剂量小檗碱组分别灌胃给予100、200 mg/kg的小檗碱；小檗碱+DKK-1组灌胃给予200 mg/kg小檗碱，同时腹腔注射2 mg/kg的DKK-1；假手术组和模型组大鼠灌胃10 mL/kg的生理盐水；每天给药1次，连续给药14 d。Zea-Longa评分法测定大鼠神经功能评分，氯化三苯基四氮唑法检测大鼠脑梗死体积百分比，末端脱氧核苷酸转移酶介导的dUTP-生物素切口末端标记法检测大鼠脑组织神经元凋亡情况，酶联免疫吸附法检测大鼠脑组织肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)，蛋白印迹法检测大鼠脑组织Wnt-1、糖原合成酶激酶-3β(GSK-3β)、β-catenin蛋白。结果 与假手术组比较，模型组大鼠Zea-Longa评分及脑组织脑...     

川芎嗪抑制大鼠脑缺血再灌注损伤的机制

目的探讨川芎嗪(TMP)抑制脑缺血再灌注损伤(CIRI)的分子机制。方法选择清洁级健康成年雄性SD大鼠,采用改良的Zea Longa栓线法构建大脑中动脉梗塞(MCAO)模型,并将大鼠随机分为三组(n=20):假手术组、模型组、TMP治疗组。假手术组大鼠不插入线栓,其余操作均同模型组;TMP治疗组大鼠在被拔出线栓再灌注时,腹腔注射TMP 20 mg/kg。再灌注24 h后,各组大鼠进行神经功能评分,然后麻醉处死,取材检测。干湿称重法检测大鼠脑组织含水量;2,3,5-三苯基氮化四氮唑(TTC)染色法检测大鼠脑梗死面积,HE染色观察脑组织形态;荧光定量PCR检测大鼠梗死侧脑皮层中miR-199a-5p、Bax、Bcl-2、肿瘤坏死因子(TNF)-α、白细胞介素(IL)-1β、IL-6 mRNA的表达水平;酶联免疫法检测大鼠血清中炎症介质TNF-α、IL-1β和IL-6的含量;免疫组化法观察大鼠梗死侧脑皮质核转录因子(NF)-κB p65及磷酸化NF-κB p65(NF-κB p-p65)的表达。结果 TMP治疗可显著改善神经缺陷评分(P<0.05),降低脑组织含水量(P<0.05),减少梗死体积(P<0.01),减轻脑组织破坏。模型组miR-199a-5p、Bax、TNF-α、IL-1β和IL-6 mRNA的表达明显升高(P<0.05),而Bcl-2 mRNA表达水平显著降低(P<0.05)。而TMP治疗可显著降低miR-199a-5p、Bax、TNF-α、IL-1β和IL-6 mRNA的表达水平(P<0.05),增加Bcl-2 mRNA的表达(P<0.05)。与模型组比较,TMP治疗组大鼠脑皮质和血清中TNF-α、IL-1β和IL-6炎症因子含量均显著降低(P<0.05)。IHC结果显示,TMP治疗组中NF-κB p-p65阳性细胞数明显减少(P<0.05)。结论 TMP可减轻CIRI,其机制可能为抑制miR-199a-5p的表达,减少凋亡,降低炎症反应,且可降低NF-κB的活化。     

淫羊藿次苷Ⅱ通过沉默信息调控子1-叉头蛋白O1通路减轻心肌缺血再灌注损伤

目的探究淫羊藿次苷Ⅱ(ICSⅡ)预处理对心肌缺血再灌注损伤大鼠的保护作用,初步探究可能的作用机制。方法将大鼠分为假手术组、模型组、淫羊藿次苷Ⅱ(ICSⅡ)组、沉默信息调控子1(SIRT1)抑制剂(Selisistat)组、ICSⅡ+Selisistat组;各组大鼠预处理后采用左冠状动脉前降支结扎法建立心肌缺血再灌注损伤模型大鼠。超声检测大鼠心室功能变化;HE染色观察大鼠心肌组织病理学变化情况;酶联免疫吸附法检测血清白细胞介素1β(IL-1β)、心肌肌钙蛋白I(cTnI)和肿瘤坏死因子α(TNF-α)水平;Tunel染色法检测心肌组织凋亡;免疫印迹法检测心肌组织中SIRT1、乙酰化叉头蛋白O1(Ac-FOXO1)、Bcl-2相关X蛋白(Bax)、天冬氨酸特异性半胱氨酸蛋白酶3(Caspase-3)、Cleaved-Caspase-3、B淋巴细胞瘤2(Bcl-2)蛋白表达情况。结果与假手术组相比,模型组左心室舒张末压(LVEDP)升高,平均动脉压(MAP)、左心室收缩压(LVSP)、左心室射血分数(LVEF)、左心室短轴缩短率(LVFS)降低,cTnI、TNF-α、IL-1β水平升高,细胞凋亡率升高,SIRT1表达降低,Ac-FOXO1表达升高,心肌组织Bax、Cleaved-Caspase-3蛋白表达升高,Bcl-2蛋白表达降低(均P0.05)。与模型组相比,ICSⅡ组LVEDP降低,MAP、LVSP、LVEF、LVFS升高,cTnI、TNF-α、IL-1β水平降低,细胞凋亡率降低,SIRT1表达升高,Ac-FOXO1表达降低,心肌组织Bax、Cleaved-Caspase-3蛋白表达降低,Bcl-2蛋白表达升高(均P0.05);Selisistat组LVEDP升高,MAP、LVSP、LVEF降低,cTnI、TNF-α、IL-1β水平升高,细胞凋亡率升高,SIRT1表达降低,Ac-FOXO1表达升高,心肌组织Bax、Cleaved-Caspase-3蛋白表达升高,Bcl-2蛋白表达降低(均P0.05)。ICSⅡ+Selisistat组LVEDP、cTnI、TNF-α、IL-1β、细胞凋亡率、Ac-FOXO1表达、心肌组织Bax、Cleaved-Caspase-3蛋白表达低于Selisistat组,MAP、LVSP、LVEF、LVFS水平和SIRT1、Bcl-2蛋白表达高于Selisistat组(均P0.05)。结论心肌缺血再灌注损伤大鼠ICSⅡ预处理后,可缓解心肌组织炎症损伤,改善心室功能,其机制可能与激活SIRT1/FOXO1通路有关。     

芒果苷对缺氧缺血性脑损伤大鼠氧化应激反应及神经细胞凋亡的影响

目的研究芒果苷通过PI3K/Akt/mTOR途径对缺氧缺血性脑损伤大鼠的氧化应激反应及神经细胞凋亡的影响。方法将144只SD新生大鼠按随机原则分为6组,空白对照组、模型组、阳性对照组、芒果苷低剂量组、芒果苷中剂量组和芒果苷高剂量组,每组24只。除空白对照组外其他各组复制缺氧缺血性脑损伤大鼠模型,造模后空白对照组和模型组给予等体积的生理盐水,阳性对照组给予尼莫地平[0.4 mg/(kg·d)],芒果苷低、中、高剂量组分别给予芒果苷50、100、200 mg/(kg·d),连续给药4周。检测各组大鼠神经功能损伤评分;干湿重法检测各组大鼠脑组织含水量;HE染色观察大鼠脑组织的病理形态学改变;原位细胞凋亡检测(TUNEL)大鼠脑组织神经元凋亡情况;生化检测法测定脑组织中超氧化物歧化酶(SOD)、丙二醛(MDA)、谷胱甘肽过氧化物酶(GSH-Px)和总抗氧化能力(T-AOC)活力;采用实时荧光定量PCR(Real-time PCR)测定大鼠脑组织内PI3K/Akt/mTOR mRNA表达;运用蛋白免疫印迹法(Western blot)检测脑组织中Caspase-3、Bcl-2、Bcl-xL、Bad、Bax蛋白含量。结果模型组大鼠的神经损伤评分、脑组织含水量、神经细胞凋亡数、MDA含量、PI3K表达及Caspase-3含量显著高于空白对照组,完整的神经元数量及脑组织中SOD、GSH-Px、T-AOC含量、Akt、mTOR表达及Bcl-2、Bcl-xL、Bad含量显著低于空白对照组(P0.01);各药物组大鼠的神经损伤评分、脑组织含水量、神经细胞凋亡数、MDA含量、PI3K表达及Caspase-3含量显著低于模型组,完整的神经元数量及脑组织中SOD、GSH-Px、T-AOC含量、Akt、mTOR表达及Bcl-2、Bcl-xL、Bad含量显著高于模型组(P0.01)。结论芒果苷通过下调Caspase-3的表达、上调Bcl-2和Bcl-xL的表达,增强PI3K/Akt/mTOR通路的表达来增强神经保护作用,抑制神经细胞凋亡,提高神经细胞存活率。     

炎症因子在尿毒症大鼠脑缺血再灌注损伤中的作用

目的观察尿毒症大鼠脑缺血再灌注(I/R)后炎症因子的动态变化。方法清洁级健康雄性Wistar大鼠30只,随机分为单纯尿毒症组(CRF组)6只、尿毒症合并脑I/R组(CRF+I/R组)24只,制备尿毒症模型,成模后,再取同样大鼠30只,随机分为正常对照组6只、单纯脑I/R组24只。将I/R组和CRF+I/R组大鼠再制作大脑中动脉栓塞模型,脑缺血2h后再灌注,按再灌注后不同时间点(0、2、12、24h)I/R组、CRF+I/R组又分为4个亚组,每个亚组6只。I/R组和CRF+I/R组按再灌注后的时间点取材,正常对照组在饲养3～7d后取材,CRF组在成模后0～3d取材,RT-PCR法检测脑组织中TNF-α、IL-1β、IL-6mRNA表达情况。结果 TNF-αmRNA:正常对照组与CRF组大鼠脑组织TNF-αmRNA的表达差异不显著(P0.05),CRF组大鼠TNF-αmRNA的表达较I/R组各时间点均降低(P0.05);脑I/R两组大鼠TNF-αmRNA在2h时间点表达最强,此后逐渐下降;CRF+I/R组大鼠各时间点TNF-αmRNA的表达均较CRF组、I/R组升高(P0.05)。IL-1βmRNA、IL-6mRNA:CRF组大鼠IL-1βmR-NA、IL-6mRNA的表达均较正常对照组升高,但差异不显著(P0.05);与I/R组各时间点相比,CRF组大鼠IL-1βmRNA、IL-6mRNA的表达均明显偏低(P0.05);脑I/R两组大鼠脑组织中IL-1β、IL-6mRNA表达随再灌注时间延长逐渐升高,至24h达高峰;与I/R组和CRF组相比,CRF+I/R组各时间点IL-1βmRNA和IL-6mRNA表达均显著升高(P0.05)。结论炎症因子参与了尿毒症大鼠的脑I/R损伤,提示尿毒症的微炎症状态对神经系统具有一定的影响。     

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.