粒细胞集落刺激因子动员骨髓干细胞治疗急性心肌梗死的观察

目的探讨粒细胞集落刺激因子(G-CSF)动员的骨髓来源干细胞对急性心肌梗死(AMI)的治疗作用.方法 27例AMI病人随机分为治疗组和对照组,治疗组连续3 d给予G-CSF 300 μg/d,用201Tl心肌显像比较两组第6天和第30天的梗死面积变化,超声心动图观察3 d内和3个月的心功能变化.结果治疗组第30天的核素梗死缺损区面积明显减少(P＜0.01),核素放射性计数百分比明显增加(P＜0.05),治疗组治疗后各项心功能指标均明显改善(P＜0.01).对照组无明显改变(P＞0.05).结论用G-CSF动员骨髓干细胞可再生成心肌组织,明显缩小AMI的梗死面积及改善心功能.     

骨髓干细胞动员对急性心肌梗死后左室重构影响的临床研究

目的 :观察骨髓干细胞动员对急性心肌梗死 (AMI)患者左室重构的影响。方法 :4 8例AMI患者随机分为动员组 (2 5例 )和对照组 (2 3例 ) ,动员组连续 3d给予粒细胞集落刺激因子 (G CSF) 30 0 μg/d ,用2 0 1Tl静息—再分布心肌显像比较两组第 6d、 30d的梗死面积 ,超声心动图观察 72h内和 3个月的左室舒张末期容积指数 (LVEDVI)、收缩末期容积指数 (LVESVI)、室壁运动指数 (WMSI)、射血分数(LVEF)。结果 :动员组治疗后心肌梗死面积明显减少 (0 383± 0 0 77vs 0 5 6 1± 0 0 96 ,P <0 0 1) ,LVESVI减少 [(2 7 4 7± 7 86 )ml/m2 vs (34 5 0± 8 0 8)ml/m2 ,P <0 0 5 ],WMSI减少 (1 10± 0 11vs 2 2 6±0 14 ,P <0 0 1) ,LVEF增加 (0 5 9± 0 0 7vs 0 4 8± 0 0 7,P <0 0 1)。结论 :应用G CSF动员AMI患者自身骨髓干细胞可明显缩小心肌梗死面积及有效防治左室重构     

冠状动脉慢血流现象与焦虑抑郁的关系

目的：探讨冠状动脉慢血流(CSF)现象与焦虑抑郁的关系。方法：入选我院心血管内科经冠脉造影结果证实的CSF患者73例,另选同期经冠脉造影结果证实冠状动脉血流正常者(NCF)73例。两组入选者均行汉密尔顿焦虑抑郁评分检查。结果：CSF组HAMA评分明显高于NCF组（17.59?±4.82 vs 10.67?±?3.79,P<0.05）,CSF组HAMD评分明显高于NCF组（23.02?±?6.01 vs 11.68±?4.09,P<0.05）,组间比较差异有显著性统计学意义。CSF组Hcy水平明显高于NCF组（16. 91±4.78 vs10.53±3.71,P<0.05）,CSF组LP-PLA2水平明显高于NCF组（257.91?±5?7.94 vs 181.25±?45.06,P<0.05）,组间比较差异有显著性统计学意义。Pearson相关性分析显示,HAMA与CSF的冠脉血流速度呈负相关关系(r=0.83,P＜0.05),HAMD与CSF的冠脉血流速度呈负相关关系(r=0.79,P＜0.05)。结论：CSF现象与焦虑抑郁呈显著性相关关系,焦虑抑郁可能参与了冠状动脉慢血流的发病。     

静态心肌灌注-代谢显像评价心肌梗死后经冠状动脉介入骨髓干细胞移植治疗的价值

目的:应用心肌灌注-代谢显像评价心肌梗死(AMI)后经冠状动脉介入移植治疗的疗效。方法:应用单光子发射型断层扫描(SPECT)静态心肌灌注代谢显像对比观察经冠状动脉成形术(PCI)+支架(stent)+心肌骨髓干细胞移植(MBMC)前后的心肌梗死区心肌血流灌注和代谢变化。结果:介入移植治疗前灌注缺损106节段,代谢缺损80节段;介入治疗后灌注缺损84节段,代谢缺损66节段,治疗前后灌注代谢差异无统计学意义(χ2=0.033,P>0.05);介入移植治疗前后人均灌注缺损分别是(3.13±1.14)节段和(2.54±1.30)节段,2组差异有统计学意义(P=0.0005);介入移植治疗前后人均代谢缺损分别是(2.42±1.28)节段和(2±1.28)节段,2组差异有统计学意义(P=0.004)。介入移植治疗后定量分析靶心图灌注显像的总记分(SPS)、代谢显像的总记分(SMS)以及严重度记分(SSS)较治疗前均有下降,但无统计学意义(P=0.184,P=0.608,P=0.166)。结论:静态心肌灌注-代谢显像是观察经冠状动脉介入移植治疗AMI疗效的一种方法。     

骨髓干细胞移植通过基质金属蛋白酶及其抑制剂降低大鼠缺血性心力衰竭心室重构

目的探讨骨髓干细胞通过调节基质金属蛋白酶2/基质金属蛋白酶抑制剂1(MMP2/TIMP1)系统改善急性心肌梗死后心力衰竭心室重构。方法结扎雌性 SD 大鼠左冠状动脉制作急性心肌梗死模型。4周后随机分为2组:移植组大鼠7只,移植雄性 SD 大鼠来源的骨髓干细胞(5×10~6)到梗死后瘢痕区。对照组大鼠7只,移植等体积的 PBS 到瘢痕心肌。通过 HE 染色和 Masson 染色评价左室形态。免疫组织化学分析心肌 MMP2和 TIMP1和瘢痕区Ⅰ、Ⅲ型胶原表达情况。经Western 杂交检测 MMP2和 TIMP1蛋白变化。结果部分骨髓干细胞在移植后21天呈纤维母细胞样生长。移植后早期有炎症细胞聚集在瘢痕区,移植后7天炎症细胞减少。与对照组相比,移植组大鼠左室射血分数和左室短轴缩短率提高[(63.43±3.97)%与(36.20±3.99)%,(31.71±1.98)%与(18.00±2.07)%,P<0.05],左室压力下降最大值(dp/dt_(min))降低[(-4756.24±270.00)mm Hg/s(1 mm Hg=0.133 kPa)与(-2789.53±624.13)mm Hg/s,P<0.05],左室厚度率增加[(76.34±2.66)%与(64.37±2.36)%,P<0.05],梗死区面积缩小[(36.19±0.83)%与(42.12±1.88)%,P<0.05]。移植组大鼠瘢痕区Ⅰ型胶原表达升高,Ⅲ型胶原降低;心肌 MMP2蛋白水平降低而TIMP1水平升高。结论骨髓干细胞移植通过 MMP2/TIMP1导致胶原网络的动态变化,从而改善急性缺血后衰竭心脏的左室重构。     

粒细胞集落刺激因子治疗急性心肌梗死的实验研究

目的探讨注射人重组粒细胞集落刺激因子(granulocytecolony-stimulatingfactorG-CSF)动员自体骨髓干细胞对实验急性心肌梗死作用。方法健康杂种猪6头,结扎左冠状动脉前降支距终末端1/3稍高处制成心肌梗死模型,随机分为治疗组及对照组。治疗组注射G-CSF,对照组注射等容积的生理氯化钠溶液。于术前、术后1日、2日、术后1周及术后4周分别测肌酸激酶及其同工酶。术前、术后1周及术后4周分别测左心室射血分数及心肌梗死面积。4周后取出心脏,作病理检查,测定心肌毛细血管密度及对心肌增殖细胞计数。结果治疗组心肌梗死面积缩小,左心室射血分数提高,和对照组比较有统计学意义(P<0.05);治疗组每视野梗死区血管数为(6.2±2.2)根,而对照组为(2.7±1.8)根,差异有统计学意义(P<0.01);治疗组梗死区每视野增殖细胞(Ki-67阳性)数为(5.1±1.4)个,而对照组为(2.4±1.3)个,差异有统计学意义(P<0.01);术后第1天猪心肌肌酸激酶及其同工酶达到高峰,以后逐渐下降,在术后4周基本下降到正常水平。治疗组和对照组差异无统计学意义(P>0.05)。结论注射G-CSF可缩小心肌梗死面积,改善心射血功能,促进心肌梗死处血管再生及细胞增殖,对心肌酶学无明显影响。     

分泌型与包涵体型粒细胞集落刺激因子对骨髓干细胞动员效率的比较

目的观察两种不同粒细胞集落刺激因子(G CSF)动员剂(分泌型与包涵体型)对急性心肌梗死(AMI)患者骨髓血干细胞动员效率。方法一组予以包涵体型G CSF(商品名惠尔血)300μg(包涵体型G CSF组),每日2次,皮下注射,连续5天;另一组予以分泌型G CSF(商品名金磊赛强)300μg(分泌型G CSF组),每日2次,皮下注射,连续5天。第6日经美国Baxter公司生产的CS3000PLUS血细胞分离机,分离外周血干细胞,采集外周血干细胞悬液经流式细胞仪测定CD34+的细胞数量。结果给G CSF前及给G CSF后第3、4、5、6天两组间外周血中细胞表面标记蛋白CD34+细胞数量和白细胞计数无明显统计学差异;在应用两组不同的动员剂后,外周血中白细胞计数与动员时间变化曲线显示曲线高峰在动员后第5天;在包涵体型G CSF组,CD34+细胞数量与时间变化曲线高峰为第5天,但在分泌型G CSF组,CD34+细胞数量与时间变化曲线显示CD34+细胞数量在3～4天内呈急剧升高趋势,但在第5天后升幅明显减缓;显示分泌型G CSF组动员后外周血中干细胞下降较慢;患者外周血中CD34+细胞数量与白细胞计数变化呈正相关(r=0.835),与性别、体重、年龄及AMI发生时间无显著性相关。结论在AMI患者中应用两种不同G CSF动员剂,两组在外周血干细胞动员效率方面无明显统计学差异。     

骨髓间充质干细胞联合肝细胞生长因子对心肌梗死治疗作用的实验研究

目的研究经非梗死相关动脉注入骨髓间充质干细胞(BMMSCS)联合肝细胞生长因子移植对心肌梗死的治疗作用。方法苏中幼猪18头,分为三组:单纯治疗组,联合治疗组及对照组,三组均经开胸结扎冠状动脉前降支制作心肌梗死模型,两组治疗组结扎后2周抽取骨髓分离培养骨髓间充质干细胞,并在结扎后4周经非梗死相关动脉注入梗死心肌(剂量5×106/ML),联合组同时注入肝细胞生长因子(HGF,4×109PFU),对照组则注入同样量的细胞培养液(IMDM);两组均在结扎后4周和8周行冠状动脉造影与门控心肌显像评价侧支循环和心功能,并在8周处死动物,取心脏标本,行免疫组化检查。结果(1)免疫组化结果显示:在两组治疗组与对照组梗死周边区均可见新生血管,但两组治疗组的新生血管密度高于对照组(P<0.05)。(2)门控心肌显像:治疗前两组治疗组与对照组LVEF无明显区别,无统计学意义(P>0.05);治疗后两组治疗组LVEF明显优于对照组,有统计学意义(P<0.05);两治疗组治疗前后LVEF明显好转(P<0.05),对照组前后LVEF无明显变化(P=0.035)。(3)冠状动脉造影显示:三组治疗前后侧支循环级别无统计学意义。结论经非梗死相关动脉BMMSCS联合肝细胞生长因子移植能够促进梗死心脏心功能改善和促进血管再生,但不能促进侧支血管的生成;同时联合治疗效果并不优于单纯干细胞治疗。     

合用开博通和螺内脂对扩张型心肌病心肌纤维化及心功能的影响

目的评价血管紧张素转换酶抑制剂开博通及醛固酮拮抗剂螺内脂逆转原发性扩张型心肌病(DCM)心肌纤维化及改善心功能的作用。方法放射免疫法测定45例原发性DCM患者应用开博通及螺内脂治疗前及治疗6个月后血清心肌纤维化指标:血清Ⅲ型前胶原(PCⅢ)、层粘连蛋白(LN)、透明质酸(HA);超声测定左心室内径、左心房内径、右心室内径及左心室射血分数(LVEF)。结果应用开博通及螺内脂治疗后血清心肌纤维化指标显著下降:PCⅢ(243.4±50.3 vs 186.6±38.4P<0.01)、LN(224.7±50.1 vs 160.8±36.8P<0.01)、HA(259.4±70.4 vs 173.4±40.6P<0.01);心功能明显改善:左心室内径(62.4±11.4 vs 51.6±10.2P<0.05)、左心房内径(48.6±10.3 vs 40.7±8.9P<0.05)、右心室内径(30.4±7.3 vs 23.4±5.7P<0.05)、LVEF(36.5±9.6 vs 41.8±11.8P<0.05)。结论开博通及螺内脂能明显逆转原发性DCM心肌纤维化,改善其心功能。     

核素运动试验血压反应与其灌注异常程度的关系

目的:探讨核素运动试验中,心肌灌注异常患者的血压反应变化特点及其定量关系. 方法:行锝99m-MIBI心肌灌注扫描运动试验者204例,其中122例核素灌注异常,82例正常,比较核素灌注正常与异常对照组运动试验中血压反应以及灌注异常节段的数量变化及半定量关系. 结果:(1)核素灌注异常组的运动后恢复期收缩压及舒张压反应(SBPR及DBPR)均明显高于核素正常对照组(P均＜0.05);(2)在核素灌注异常组中,持续性放射减低或缺损组(梗死亚组)的SBPR明显高于可逆性放射减低或缺损组(缺血亚组)(0.885±0.161比0.814±0.119,P＜0.01);(3)核素灌注异常组中,随异常节段数增加SBPR递增(＞3段亚组0.879±0.148比1～3段亚组0.801±0.120,P＜0.01,且两者明显高于0段亚组);(4)核素灌注异常多因素逐步回归中,SBPR为进入方程相关性最强因素(β=0.27,P=0.001). 结论:心肌缺血/梗塞患者在运动试验中,SBPR不但明确增高,而且还与缺血/梗塞的心肌节段数明显相关     

Three layer functional model and energy exchange concept of aging process

Relying on a certain degree of abstraction, we can propose that no particular distinction exists between animate or living matter and inanimate matter. While focusing attention on some specifics, the dividing line between the two can be drawn. The most apparent distinction is in the level of structural and functional organization with the dissimilar streams of ‘energy flow’ between the observed entity and the surrounding environment. In essence, living matter is created from inanimate matter which is organized to contain internal intense energy processes and maintain lower intensity energy exchange processes with the environment. Taking internal and external energy processes into account, we contend in this paper that living matter can be referred to as matter of dissipative structure, with this structure assumed to be a common quality of all living creatures and living matter in general. Interruption of internal energy conversion processes and terminating the controlled energy exchange with the environment leads to degeneration of dissipative structure and reduction of the same to inanimate matter, (gas, liquid and/or solid inanimate substances), and ultimately what can be called ‘death.’ This concept of what we call dissipative nature can be extended from living organisms to social groups of animals, to mankind. An analogy based on the organization of matter provides a basis for a functional model of living entities. The models relies on the parallels among the three central structures of any cell (nucleus, cytoplasm and outer membrane) and the human body (central organs, body fluids along with the connective tissues, and external skin integument). This three-part structural organization may be observed almost universally in nature. It can be observed from the atomic structure to the planetary and intergalactic organizations. This similarity is corroborated by the membrane theory applied to living organisms. According to the energy nature of living matter and the proposed functional model, the decreased integrity of a human body's external envelope membrane is a first cause of the structural degradation and aging of the entire organism. The aging process than progresses externally to internally, as in single cell organisms, suggesting that much of the efforts towards the restoration and maintenance of the mechanisms responsible for structural development should be focused accordingly, on the membrane, i.e., the skin. Numerous reports indicate that all parts of the human body, like: bones, blood with blood vessels, muscles, skin, and so on, have some ability for restoration. Therefore, actual revival of not only aging tissue of the human body's membrane, but the entire human body enclosed within, with all internal organs, might be expected. We assess several aging theories within the context of our model and provide suggestions on how to activate the body's own anti-aging mechanisms and increase longevity. This paper presents some analogies and some distinctions that exist between the living dissipative structure matter and inanimate matter, discusses the aging process and proposes certain aging reversal solutions.     

Unusual responses of nocturnal pineal melatonin synthesis and secretion to swimming: Attempts to define mechanisms

Abstract: The effect of swimming at night on rat pineal melatonin synthesis was compared with that of light exposure at night. Rats were forced to swim at 0030 hr (lights out at 2000 hr) and sacrificed by decapitation 15 and 30 min later, immediately after swimming. Other groups of animals were exposed to white light (650μW/cm²) for 15 and 30 min at same time. Swimming caused a rapid and highly significant drop in the melatonin content in the pineal gland; however, the activity of N-acetyltransferase (NAT), the supposed rate limiting enzyme in the melatonin production, was not changed. Despite the drop in pineal melatonin levels, serum concentrations of the indole remained elevated in the rats that swam. In contrast, melatonin levels in the pineal and serum of light exposed rats fell precipitously, accompanied by a significant suppression of NAT activity. Since we anticipated that the strenuous exercise associated with swimming may induce release of artrial natriuretic peptide (ANP) from the heart, which in turn could cause the release of pineal melatonin, in a second study we injected physiological saline intravenously to stretch the cardiac muscle and release ANP. Three milliliters of normal saline was injected during the day into the jugular vein of anesthetized rats that were pretreated with isoproterenol to stimulate pineal melatonin production. Animals were killed 15 min after the saline injection, and pineal NAT activity and pineal melatonin levels were measured. The saline injections caused no alteration in the elevated levels of either NAT or melatonin. These data suggest that the disparity in pineal NAT activity (which was high) and pineal melatonin (which was low), in animals swum at night, may not be caused by ANP which is released during strenuous exercise such as swimming.     

Melatonin and photoperiodic time measurement: Seasonal breeding in the sheep

Abstract: Well-established circadian physiology supports the view that photoperiodic time measurement utilizes the coincidence between the presence of light and a photosensitive phase of a 'biological clock' to alter reproductive status—the so-called external coincidence model of seasonal breeding. In this review, we examine the mechanism whereby photoperiod interacts with presumed suprachiasmatic nuclei activity to allow endogenous melatonin to normally synchronize reproductive activity to the optimal time of year. The Romney Marsh sheep is particularly explored as an experimental model. It is suggested that the on/off activity of seasonal reproduction may be a robust mechanism able to be predictably manipulated by the judicious use of the light/dark cycle and exogenous melatonin, but firmly based on circadian principles.     

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.     

Serological survey of HIV and syphilis in pregnant women in Madagascar

Objectives Peripartal transmission of human immunodeficiency virus (HIV) and Treponema pallidum, the causative agent of syphilis, leads to severe consequences for newborns. Preventive measures require awareness of the maternal infection. Although HIV and syphilis testing in Madagascar could be theoretically carried out within the framework of the national pregnancy follow‐up scheme, the required test kits are rarely available at peripheral health centres. In this study, we screened blood samples of pregnant Madagascan women for HIV and syphilis seroprevalence to estimate the demand for systemic screening in pregnancy. Methods Retrospective anonymous serological analysis for HIV and syphilis was performed in plasma samples from 1232 pregnant women that were taken between May and July 2010 in Ambositra, Ifanadiana, Manakara, Mananjary, Moramanga and Tsiroanomandidy (Madagascar) during pregnancy follow‐up. Screening was based on Treponema pallidum haemagglutination tests for syphilis and rapid tests for HIV, with confirmation of positive screening results on line assays. Results Out of 1232 pregnant women, none were seropositive for HIV and 37 (3%) were seropositive for Treponema pallidum. Conclusions Our findings are in line with previous studies that describe considerable syphilis prevalence in the rural Madagascan population. The results suggest a need for screening to prevent peripartal Treponema pallidum transmission, while HIV is still rare. If they are known, Treponema pallidum infections can be easily, safely and inexpensively treated even in pregnancy to reduce the risk of transmission.     

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.