卡维地洛对慢性心力衰竭患者血管内皮功能及细胞因子的影响

目的观察卡维地洛对慢性心力衰竭(chronic heart failure,CHF)患者血管内皮功能的影响,同时观察卡维地洛对患者细胞因子的影响以及与心功能的相关性.方法入选CHF患者52例,随机分为常规抗CHF治疗组(25例)和卡维地洛组(27例),后者在常规抗CHF治疗基础上加用卡维地洛.疗程为12周.正常对照组为健康者(26例).所有CHF患者治疗前后均测定左室舒张末期内径(LVDd)和收缩末期内径(LVDs)、左室射血分数(LVEF)、肱动脉反应性充血状态下血管内径和血流量的变化、血一氧化氮(nitrogen monoxide,NO)、内皮素(endothelin,ET 1)、肿瘤坏死因子(tumor necrosis factor-α,TNF-α)、白介素-6(interleukin-6,IL-6)等指标.结果CHF患者肱动脉反应性充血状态下血管内径扩张程度和血流量增加程度均低于正常对照组(P＜0.01),CHF患者血NO、ET 1、TNF-α、IL-6等指标均高于正常对照组(P ＜0.01).12周治疗后,卡维地洛组改善肱动脉反应性充血状态下血管内径扩张程度和血流量增加程度均优于常规抗CHF治疗组(P＜0.01),改善LVDd、LVDs和LVEF均优于常规抗CHF治疗组(P＜0.01).同时,卡维地洛组ET-1、IL-6等指标的下降也优于常规抗CHF治疗组(P＜0.01或P＜0.05).另外,52例CHF患者治疗前LVEF值与TNF-α值或IL-6值存在一定的负相关,相关系数分别是r=-0.55(P＜0.01)和r=-0.57(P＜0.01).结论CHF患者存在着内皮功能紊乱,TNF-α及IL-6等细胞因子被激活;卡维地洛可有效改善CHF患者的心功能和血管内皮功能,缩小心腔,降低TNF-α及IL-6等细胞因子.     

卡维地洛对不稳定性心绞痛患者血管内皮功能及炎症标志物的影响

目的:观察卡维地洛对不稳定性心绞痛患者血管内皮功能及炎症标志物的影响。方法:采用随机、对照和单盲方法将86例不稳定性心绞痛患者分为常规治疗组(n=43)和卡维地洛组(n=43)。疗程均为4周。治疗过程中有6例被剔除,其中常规治疗组4例,卡维地洛组2例。正常组(20例)不予任何治疗。治疗前后分别采用高分辨率血管超声检测肱动脉血流介导性舒张功能变化,测定血中高敏C反应蛋白(hsCRP)、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)含量。结果:①不稳定性心绞痛患者肱动脉血流介导性舒张功能较正常人明显减弱[(5.8±2.7)%比(13.8±3.6)%,P＜0.001],hS-CRP、TNF-α及IL-6水平明显高于正常组(P均＜0.01)。②常规治疗组和卡维地洛组治疗前肱动脉血流介导性舒张功能无显著差异。治疗后卡维地洛组肱动脉血流介导性舒张功能明显增强,与治疗前比较有非常显著性差异[(5.7±2.1)%比(8.6±1.8)%,P＜0.001],而常规治疗组治疗前后无明显变化。治疗后肱动脉血流介导性舒张功能增强与hsCRP、TNF-α、IL-6含量减少具有明显相关性(r=-0.68、-0.62、-0.65,P均＜0.01)。③卡维地洛治疗后血中hsCRP、TNF-α、IL-6含量均显著降低(P均＜0.01),而常规治疗前后则无明显差异(P均＞0.05)。结论:不稳定性心绞痛患者的血管内皮损伤与炎症具有密切关系。卡维地洛对不稳定性心绞痛患者具有明显的改善内皮功能作用和抗炎效应。抗炎作用可能是卡维地洛重要的药理作用之一。     

卡维地洛联合阿托伐汀对冠心病心力衰竭患者血管内皮功能的影响

目的观察卡维地洛和阿托伐汀联合治疗对冠心病慢性心力衰竭患者血管内皮功能的和心功能影响。方法冠心病心力衰竭患者60例，均给予常规抗心力衰竭治疗，分为3组：常规组16例；卡维地洛组22例，加用卡维地洛；联合用药组22例，加用卡维地洛和阿托伐汀。治疗前后均测定左心室舒张末期内径和左心室收缩末期内径、左心室射血分数及肱动脉血流介导的扩张反应。结果治疗12周后，3组患者治疗后肱动脉血流介导的扩张反应均高于治疗前，而3组治疗后左心室舒张末期内径、左心室收缩末期内径和左心室射血分数均较治疗前有改善：血流介导的扩张反应联合用药组的肱动脉改善较卡维地洛组明显（P〈0．05），卡维地洛组优于常规组（P〈0．01）。结论冠心病心力衰竭患者存在内皮功能障碍，卡维地洛可改善其心功能和血管内皮功能，缩小心腔径。这些效应在联合阿托伐汀治疗时更为明显。     

卡维地洛联合阿托伐汀对冠心病心力衰竭患者血管内皮功能的影响

目的观察卡维地洛和阿托伐汀联合治疗对冠心病慢性心力衰竭患者血管内皮功能的和心功能影响。方法冠心病心力衰竭患者60例，均给予常规抗心力衰竭治疗，分为3组：常规组16例；卡维地洛组22例，加用卡维地洛；联合用药组22例，加用卡维地洛和阿托伐汀。治疗前后均测定左心室舒张末期内径和左心室收缩末期内径、左心室射血分数及肱动脉血流介导的扩张反应。结果治疗12周后，3组患者治疗后肱动脉血流介导的扩张反应均高于治疗前，而3组治疗后左心室舒张末期内径、左心室收缩末期内径和左心室射血分数均较治疗前有改善：血流介导的扩张反应联合用药组的肱动脉改善较卡维地洛组明显（P〈0．05），卡维地洛组优于常规组（P〈0．01）。结论冠心病心力衰竭患者存在内皮功能障碍，卡维地洛可改善其心功能和血管内皮功能，缩小心腔径。这些效应在联合阿托伐汀治疗时更为明显。     

卡维地洛对慢性心衰患者糖、脂代谢的影响

目的观察卡维地洛对慢性心衰患者的疗效及其对血糖,血脂代谢的影响。方法入选CHF患者59例,随机分为对照组:应用常规抗CHF治疗组(30例)和卡维地洛组(29例),后者在常规抗CHF治疗基础上加用卡维地洛,疗程为24周,治疗前后均测定左室舒张末期内径(LVDd)和收缩末期内径(LVDs)、左室射血分数(LVEF)、空腹血糖(FBS)、糖化血红蛋白(HbAlc)、血脂。结果卡维地洛组改善LVDd、LVDs和LVEF均优于常规抗CHF治疗组(P<0.01),治疗后卡维地络组TC、LDL-C较对照组降低(P<0.05)。结论卡维地洛可有效改善CHF患者的心功能,对糖、脂代谢有一定的益处。     

不同剂量比索洛尔对心力衰竭患者神经内分泌及炎症细胞因子的影响

目的:评价不同剂量比索洛尔对慢性收缩性心力衰竭(心衰)患者神经内分泌活性、细胞因子、心功能和心脏事件的影响.方法:120例慢性心功能不全患者,在常规治疗心衰的前提下,随机分为小剂量比索洛尔组[平均(3.5±1.2)mg]和大剂量比索洛尔组[平均(8.5±1.2)mg],每组60例,观察其对去甲肾上腺素、血浆肾素活性、血管紧张素Ⅱ、醛固酮、内皮素、白细胞介素-6、肿瘤坏死因子-α、心钠素、脑钠素、心功能及心脏事件的影响.结果:两组治疗后与治疗前比心率均有显著下降(P均<0.05).大剂量比索洛尔组左心室射血分数、心排出量、短轴缩短率、左心室舒张末期内径、左心室收缩末期内径、纽约心功能分级及神经内分泌水平治疗后与治疗前相比有显著改善(P均<0.05).而小剂量比索洛尔组治疗前后上述参数均无显著变化(P均<0.05).随访二年,大剂量比索洛尔组1例心源性死亡,因心衰恶化再入院12例,而小剂量比索洛尔组6例心源性死亡,因心衰恶化再入院24例,死亡和再入院复合终点两组间均达极显著差异(P均＜0.001).结论:与小剂量比索洛尔相比,大剂量比索洛尔对神经内分泌及细胞因子抑制更大,心功能改善更好,心脏事件显著减少.     

依那普利联合卡维地洛对慢性心力衰竭患者心功能、神经内分泌功能及血管内皮功能的影响研究

目的探讨依那普利联合卡维地洛对慢性心力衰竭(CHF)患者心功能、神经内分泌功能及血管内皮功能的影响。方法选取2012年3月—2013年3月平顶山市第二人民医院收治的CHF患者94例,随机分为治疗组和对照组,各47例。对照组患者在常规治疗基础上采用依那普利治疗,治疗组患者在常规治疗基础上给予依那普利联合卡维地洛治疗,3个月为1个疗程,共治疗2个疗程。比较两组患者临床疗效,治疗前后心功能、神经内分泌功能及血管内皮功能指标,观察两组患者治疗期间药物不良反应发生情况。结果治疗组患者临床疗效优于对照组(u=2.546,P0.05)。治疗前两组患者左心室舒张末期内径、左心室收缩末期内径、左心房内径、左心室射血分数及左心室短轴缩短率比较,差异无统计学意义(P0.05);治疗后治疗组患者左心室舒张末期内径、左心室收缩末期内径及左心房内径小于对照组,左心室射血分数和左心室短轴缩短率高于对照组(P0.05)。治疗前两组患者血浆肾素活性、血管紧张素Ⅱ及醛固酮水平比较,差异无统计学意义(P0.05);治疗后治疗组患者血浆肾素活性、血管紧张素Ⅱ及醛固酮水平低于对照组(P0.05)。治疗前两组患者充血后肱动脉内径、含服硝酸甘油后肱动脉内径、反应性充血后肱动脉内径变化率及含服硝酸甘油后肱动脉内径变化率比较,差异无统计学意义(P0.05);治疗后治疗组患充血后肱动脉内径、含服硝酸甘油后肱动脉内径、反应性充血后肱动脉内径变化率及含服硝酸甘油后肱动脉内径变化率大于对照组(P0.05)。治疗期间对照组患者不良反应发生率为6.4%,与治疗组的8.5%比较,差异无统计学意义(P0.05)。结论依那普利联合卡维地洛能有效改善CHF患者心功能、神经内分泌功能及血管内皮功能,从而提高临床疗效,且安全性较高。     

卡维地洛对慢性心衰神经内分泌、心功能及血管内皮功能的影响

目的：观察卡维地洛对慢性心衰患者神经内分泌、心功能及血管内皮功能的影响。方法：60例慢性心力衰竭患者随机分为常规治疗对照组（常规组，30例）和卡维地洛组（30例）。对照组给予洋地黄、利尿剂、血管紧张素转化酶抑制剂等常规治疗，卡维地洛组在给予常规治疗的基础上加用卡维地洛。治疗前及治疗6个月后放射免疫法测定血浆血管紧张素Ⅱ（AngⅡ）及内皮素-1（ET-1）水平，超声心动图检测心功能，血管超声检测肱动脉血管内皮功能的变化。结果：两组治疗后较治疗前AngⅡ及ET-1水平显著降低（P〈0．01），卡维地洛组改善更明显（P〈0．01）；两组左房内径、左室舒张末期内径（LVEDd）和左室收缩末期内径（LVESd）明显缩短，左室射血分数（LVEF）显著增高，但两组间无显著差异（P〉0．05）；卡维地洛能显著改善血管内皮功能（P〈0．01），且较常规治疗组明显（P〈0．01）。结论：卡维地洛抑制心衰患者的神经内分泌激活，逆转心室重塑，改善心功能和血管内皮功能。     

不同危险度的高血压病人血管内皮功能

目的根据"内皮-高血压-心血管事件"链的病理发展进程,进一步了解高血压病与血管内皮功能的相互关系,以及降压药物对高血压患者血管内皮功能的影响.方法 54例高血压患者按危险性分组,其中低中危组32例,高极高危组22例,对照组30例.采用超声测量3组肱动脉内皮依赖性舒张功能,并测定血浆内皮素、血管性血友病因子.然后采用氨氯地平或氨氯地平 卡维地洛治疗,12周以后复查上述指标.结果静息状态下,3组间肱动脉内径、流量无明显差异;压迫后高极高危组内径扩张程度低于对照组(6.6%vs 12.1%;P＜0.01),低中危组与对照组无显著性差异(10.2%vs 12.1%;P＞0.05);血浆内皮素、血管性血友病因子在高极高危组较对照组有显著升高(P＜0.05),低中危组与对照组相似(P＞0.05);经氨氯地平和卡维地洛治疗12周,血压下降,肱动脉超声内皮功能和血液内皮标志物均有改善.结论高血压患者内皮功能受损与血压增高和伴随的靶器官损伤有关.降压治疗可改善高血压患者血管内皮功能.     

老年慢性心力衰竭患者肾小球滤过功能改变及卡维地洛干预的观察

目的 评价老年慢性心力衰竭(心衰)患者肾小球滤过功能的变化及卡维地洛对老年慢性心衰患者肾功能的影响.方法 入选老年慢性心衰患者47例(慢性心衰组),健康体格检查的非慢性心衰患者22例(非慢性心衰组),分别检测血尿酸(SUA)、血肌酐(Scr),C-G法计算肾小球滤过率(GFR),确定显性肾功能不全(ORI)、隐匿性肾功能不全(CRI)、总肾功能不全(TRI)的发生率.慢性心衰组患者再随机分为卡维地洛组和非卡维地洛组,观察卡维地洛治疗3个月后的左室舒张末内径(LVEDD)、左室射血分数(LVEF)及肾小球滤过功能变化.结果 慢性心衰组ORI和TRI发生率均高于非慢性心衰组(ORI分别为55.3%和22.7%,χ2=6.43,P＜0.05;TRI分别为80.9%和40.9%,χ2=11.01,P＜0.01),但CRI发生率的差异无统计学意义(25.5%和18.1%,χ2=0.45,P＞0.05);慢性心衰组SUA、Scr高于非慢性心衰组[SUA分别为(472.8±100.2)和(415.3±71.4)mmol/L,P＜0.05 Scr分别为(150.7±68.0)和(108.5±43.2)mmol/L,P＜0.01],GFR低于非慢性心衰组[分别为(42.9±20.7)和(59.3±30.1)ml/min,P＜0.05)];与治疗前比较,卡维地洛组治疗3个月后的SUA[(407.5±57.7)mmol/L和(476.4±85.2)mmol/L,P＜0.01]、Scr[(113.5±55.4)mmol/L和(152.0±74.6)mmol/L,P＜0.01]均显著下降,GFR升高[(57.9±23.7)ml/min和(45.0±22.6)ml/min,P＜0.01];治疗3个月后,卡维地洛组SUA、Scr均显著低于同期的非卡维地洛组(均为P＜0.05),GFR高于非卡维地洛组(P＜0.01).结论 老年慢性心衰患者肾小球滤过功能下降.在充分抗心衰治疗的基础上,加用卡维地洛可以改善慢性心衰患者的肾小球滤过功能.     

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.