环孢霉素A抑制肾性高血压大鼠心肌肥大的作用机制

目的观察环孢霉素A对肾性高血压大鼠心肌肥大的抑制作用,并探讨其作用机制.方法 20只Wistar大鼠随机分为3组两组采用一肾一夹模型制造肾性高血压,其中高血压组(n=7)予生理盐水腹腔注射;CsA组(n=7)给予环孢霉素A(CsA)5 mg·kg-1·d-1腹腔注射;假手术组(n=6)只给予生理盐水腹腔注射.称重法测定心重比,发色底物法测CaN活性;半定量PCR测定各组心肌组织中心房利钠因子(ANF)及CaNmRNA的水平,同时用免疫组织化学染色方法,观察心肌中CaN及活化T细胞核因子(nuclearfactor of activated T cell,NFAT)的表达.结果肾性高血压大鼠经CsA干预4周,其心重比较未干预组明显降低(P＜0.05),ANF mRNA水平较手术组明显降低(P＜0.05),与假手术组水平接近,心肌肥大受到抑制,同时发现心肌中CaN活性较未干预组显著下降,CaN mRNA水平较手术组明显降低(P＜0.05),免疫组化显示CsA干预组心肌中CaN及NFAT表达降低.结论 CsA抑制肾性高血压心肌肥大的机制与其下调心肌胞浆中CaN表达及其活性有关.     

环孢霉素A抑制肾性高血压大鼠心肌肥大的作用机制

目的　观察环孢霉素A对肾性高血压大鼠心肌肥大的抑制作用 ,并探讨其作用机制。方法　 2 0只Wistar大鼠随机分为 3组 :两组采用一肾一夹模型制造肾性高血压 ,其中高血压组 (n =7)予生理盐水腹腔注射 ;CsA组 (n =7)给予环孢霉素A(CsA) 5mg·kg- 1 ·d- 1 腹腔注射 ;假手术组 (n =6)只给予生理盐水腹腔注射。称重法测定心重比 ,发色底物法测CaN活性 ;半定量PCR测定各组心肌组织中心房利钠因子 (ANF)及CaNmRNA的水平 ,同时用免疫组织化学染色方法 ,观察心肌中CaN及活化T细胞核因子 (nuclearfactorofactivatedTcell,NFAT)的表达。结果　肾性高血压大鼠经CsA干预 4周 ,其心重比较未干预组明显降低 (P <0 0 5 ) ,ANFmRNA水平较手术组明显降低 (P <0 0 5 ) ,与假手术组水平接近 ,心肌肥大受到抑制 ,同时发现心肌中CaN活性较未干预组显著下降 ,CaNmRNA水平较手术组明显降低 (P <0 0 5 ) ,免疫组化显示CsA干预组心肌中CaN及NFAT表达降低。结论　CsA抑制肾性高血压心肌肥大的机制与其下调心肌胞浆中CaN表达及其活性有关     

醛固酮上调大鼠组织钙调神经磷酸酶活性及抑制血浆一氧化氮水平

目的研究醛固酮对大鼠重要脏器心、脑、肾、脾、肺和肝脏中钙调神经磷酸酶(CaN)活性及血浆血管紧张素Ⅱ(AngⅡ)、内皮素(ET-1)和一氧化氮(NO)水平的影响,探讨醛固酮在CaN依赖的信号传导通路中的作用.方法取21只雄性Wistar大鼠随机分为3组醛固酮(Ald)组(腹腔内注射Ald 18μg/d 4周)、环孢霉素A(CsA)干预组(以Ald处理同时腹腔内给予CsA 5 mg/kg·d注射共4周)及正常对照组.采用放免法测定血浆AngⅡ、Ald和ET-1浓度,采用比色测定NO浓度及大鼠各组织器官CaN活性.结果Ald组大鼠血浆NO-3浓度较对照组明显下降(P＜0.05),CsA干预后血NO-3浓度明显回升(P＜0.05).各组AngⅡ、ET-1浓度无明显变化.Ald组大鼠心、脾、肾、肺、脑和肝脏中CaN活性较正常对照组分别上升147%、65%、38%、100%、43%和50%(均P＜0.05),CsA干预显著缓解上述组织器官CaN活性的上升(P＜0.05).结论醛固酮能上调大鼠重要组织脏器CaN活性并抑制血浆NO水平,可能在激活CaN依赖的信号传导通路中具有重要作用.     

醛固酮上调大鼠组织钙调神经磷酸酶活性及抑制血浆一氧化氮水平

目的 研究醛固酮对大鼠重要脏器心、脑、肾、脾、肺和肝脏中钙调神经磷酸酶(CaN)活性及血浆血管紧张素Ⅱ(AngⅡ)、内皮素(ET-1)和一氧化氮(NO)水平的影响，探讨醛固酮在CaN依赖的信号传导通路中的作用。方法 取21只雄性Wistar大鼠随机分为3组：醛固酮(Ald)组(腹腔内注射Ald 18μg／d 4周)、环孢霉素A(CsA)干预组(以Ald处理同时腹腔内给予CsA 5mg／kg·d注射共4周)及正常对照组。采用放免法测定血浆AngⅡ、Ald和ET-1浓度，采用比色测定NO浓度及大鼠各组织器官CaN活性。结果 Ald组大鼠血浆NO_3~-浓度较对照组明显下降(P＜0.05)，CsA干预后血NO_3~-浓度明显回升(P＜0.05)。各组AngⅡ、ET-1浓度无明显变化。Ald组大鼠心、脾、肾、肺、脑和肝脏中CaN活性较正常对照组分别上升147％、65％、38％、100％、43％和50％(均P＜0.05)，CsA干预显著缓解上述组织器官CaN活性的上升(P＜0.05)。结论 醛固酮能上调大鼠重要组织脏器CaN活性并抑制血浆NO水平，可能在激活CaN依赖的信号传导通路中具有重要作用。     

环孢素A调控肾性高血压大鼠血浆神经肽Y的作用机制

目的:探讨一肾一夹肾性高血压大鼠模型中,血浆神经肽Y（NPY）含量变化调控机制。方法:健康雄性Wistar大鼠,随机分为3组。①假手术组;②高血压组:通过一肾一夹法复制肾性高血压大鼠;③环孢素A组:环孢素A（CsA）5mg·kg-1·d-1皮下注射;全部大鼠均在实验14d后,测量尾动脉压,取心脏测量左心室质量/体质量（LVW/BW）,用放免方法测定血浆NPY、血管紧张素Ⅱ（AⅡ）、醛固酮（Ald）含量。结果:高血压组较假手术组BP、LVW/BW升高,NPY下降,Ald增加;CsA组较高血压组LVW/BW降低,NPY增加,Ald无显著变化。结论:Ald对血浆NPY水平的负性调控,是通过CaN信号转导通路介导而发生的。     

血管紧张素Ⅱ-醛固酮诱导肾性高血压大鼠心肌肥厚发生:钙调神经磷酸酶抑制因子的作用

目的:探讨一肾一夹肾性高血压大鼠模型中,心肌组织中钙调神经磷酸酶(CaN)抑制因子(calcineurin-inhibi-tor,Cain)表达的变化,以及血浆中相关活性因子的变化。方法:将21只健康雄性Wistar大鼠,随机分为3组(n=7),即假手术组、手术组(通过一肾一夹法复制肾性高血压大鼠)及螺内酯组:以螺内酯20 mg/(kg.d)灌胃;实验14 d后,大鼠称质量后抽血处死,分别计算左心室质量(LVW)、全心质量(HW)以及二者与体质量(BW)的比值。采用放射免疫测定法检测血浆醛固酮(Ald)及血管紧张素Ⅱ(AngⅡ)的含量。以蛋白印迹杂交的方法,测定心肌组织中Cain表达的变化。结果:与假手术组比较,手术组大鼠的LVW/BW及HW/BW比值显著增加(P0.05)、血浆Ald和AngⅡ的水平、及Cain的表达的显著增加(P0.01);而与手术组比较,螺内酯组大鼠的LVW/BW比值显著减少(P0.05)、血浆AngⅡ的水平及Cain的表达均显著减少(P0.01)。结论:通过一肾一夹手术,诱导机体内源性Ald和AngⅡ增加,导致大鼠心肌肥厚反应的发生。同时,机体内源性Cain表达的增加,以抑制CaN信号通路介导的心肌肥厚反应。螺内酯通过阻断Ald与其受体结合,可以抑制心肌肥厚的发生。     

螺内酯抗钙调神经磷酸酶依赖的肾性高血压大鼠心肌肥厚作用机制

目的　观察螺内酯抗钙调神经磷酸酶 (calcineurin ,CaN)依赖的肾性高血压大鼠心肌肥厚的作用。方法　 2 0只Wistar大鼠随机分为 3组 :2组采用一肾一夹模型制造肾性高血压 ,其中螺内酯组 (n =7)予螺内酯灌胃 ,高血压组 (n =7)予水灌胃 ;假手术组 (n =6 )只予水灌胃。称重法测定心重比 ,发色底物法测CaN活性 ;半定量PCR测定各组心肌组织中心房利钠因子mRNA的水平 ,同时用免疫组织化学染色方法 ,观察心肌中CaN及活化T细胞核因子的表达。结果　肾性高血压大鼠经螺内酯灌胃 4周 ,其心重比较未干预组明显降低 (P <0 0 5 ) ,心房利钠因子mRNA水平较手术组明显降低 (P <0 0 5 ) ,与假手术组水平接近 ,心肌肥厚受到抑制 ,同时发现心肌中CaN活性较未干预组显著下降 ,免疫组化显示螺内酯干预组心肌中CaN及活化T细胞核因子表达降低。结论　螺内酯抑制肾性高血压心肌肥厚的机制与其下调心肌胞浆中CaN表达及其活性有关     

钙调神经磷酸酶在肾血管性高血压大鼠心肌肥厚中的作用

目的探讨钙调神经磷酸酶(CaN)在肾血管性高血压大鼠心肌肥厚中的作用及抑制CaN活性对心肌肥厚的影响.方法制备两肾一夹肾血管性高血压大鼠模型, 术后2月, 经心脏超声证实大鼠心肌肥厚后,分别予环孢菌素A( CsA)或培多普利治疗.观察CsA、培多普利对大鼠心肌肥厚程度,CaN mRNA、蛋白质表达和CaN活性的影响.结果两肾一夹术后2月,手术组大鼠左室后壁和室间隔厚度均较假手术组增高21%(P<0.01),CsA治疗后较治疗前分别下降16%和14%(P<0.01),培多普利治疗后左室后壁和室间隔厚度亦较治疗前下降.同时大鼠左室心肌CaN mRNA和蛋白质表达、CaN活性均显著下降.结论 CaN参与肾血管性高血压大鼠心肌肥厚,抑制CaN活性可逆转心肌肥厚.     

钙调神经磷酸酶在醛固酮诱导心肌肥大中的作用

目的观察钙调神经磷酸酶(CaN)在醛固酮(Ald)诱导的心肌肥大信号转导机制中的作用及其调节。方法24只Wistar大鼠随机分为2组:实验组和对照组。实验组给予醛固酮腹腔注射后,再随机分为3组,分别给予环孢霉素A、螺内酯、及生理盐水干预,对照组仅腹腔注射生理盐水。测定大鼠血浆中血管活性因子Ald、AngⅡ、ET1与NO-3的浓度,心重/体重,心肌组织中的CaN活性;心肌组织中肥大相关基因心房利钠因子(ANF)及CaNAβmRNA的水平,同时用免疫组化方法观察心肌胞浆中CaN的表达。结果醛固酮腹腔注射后血浆中的醛固酮水平明显增高,醛固酮腹腔注射4周可使心肌肥大相关基因ANFmRNA水平明显升高,心肌中CaN活性明显升高,心肌细胞浆中的CaN表达上调;环孢霉素A及螺内酯干预4周,可明显抑制心肌CaN活性,并下调ANF(P<0.05)的表达。结论CaN参与了外源性醛固酮诱导的心肌肥大的信号通路,醛固酮通过活化CaN,使肥大相关基因表达增加产生心肌肥大。螺内酯通过拮抗醛固酮与受体结合抑制心肌肥大。     

缬沙坦对压力负荷心肌肥大钙调神经磷酸酶（CaN）通路的作用

目的探讨血管紧张素Ⅱ受体(AngⅡ,AT1及AT2)拮抗剂对致心肌肥厚的钙调神经磷酸酶(CaN)信号通路的影响。方法腹主动脉缩窄法建立大鼠压力负荷模型,实验动物分为手术组(n=8);缬沙坦组(n=8):手术组+缬沙坦(1mg/kg·d);PD123319(AT2R受体拮抗剂)组(n=8):手术组+PD123319(30mg/kg·d);假手术组(n=8)。放射免疫法检测血浆、心肌AngⅡ浓度,免疫沉淀法检测心肌钙蛋白酶(ucalpain,mcalpain)及CaN蛋白表达及其磷酸化。结果缬沙坦组血浆AngⅡ浓度显著高于假手术组及PD123319组(P<0.05),缬沙坦组心肌AngⅡ浓度则低于假手术照组及PD123319组(P<0.05)。手术组ucalpain蛋白表达显著高于假手术组(P<0.01),缬沙坦组显著低于手术组及PD123319组(P<0.05),手术组与PD123319组间差异没有显著性(P>0.05)。手术组CaN磷酸化显著高于假手术组(P<0.01),缬沙坦组显著低于手术组及PD123319组(P<0.05),手术组与PD123319组间差异没有显著性(P>0.05)。结论ucalpain参与激活高压力负荷下心肌组织CaN通路,ucalpain的上调通过AT1起作用,AT1受体拮抗剂的心脏保护作用与其抑制了m-calpain有关。     

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.     

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.     

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.     

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.