内镜下组织黏合剂治疗肝硬化食管胃底静脉曲张出血患者的预后情况分析

目的探讨肝硬化食管胃底静脉曲张(GOV)出血患者经内镜下组织黏合剂治疗的预后情况及影响因素。方法回顾性分析内蒙古边防总队医院2005年1月-2013年1月收治的128例经内镜下组织黏合剂治疗的肝硬化GOV出血患者的临床资料,统计患者再出血发生率,并根据是否发生再出血分为观察组和对照组,统计两组患者临床资料,应用SPSS 19.0统计软件分析再出血的影响因素。结果所有患者再出血率为17.2%(22/128);观察组INR1.5患者百分率显著高于对照组,门静脉右支直径8.5 mm患者百分率显著低于对照组,ALT水平、AST水平及FIB4评分均显著高于对照组,差异均具有统计学意义(P均0.05);多因素分析显示,INR1.5、门静脉右支直径8.5 mm和FIB4评分高均是内镜下组织黏合剂治疗后再出血的影响因素(P均0.05)。结论肝硬化GOV出血患者经内镜下组织黏合剂治疗后预后较好;INR1.5、门静脉右支直径8.5 mm和FIB4评分高均是影响预后的主要因素。     

肝硬化患者内镜预防食管胃静脉曲张再出血:10年经验

目的评估肝硬化食管胃静脉曲张(gastroesophageal varice, GOV)患者内镜治疗的预后。方法从数据库中检索2004年1月1日至2013年12月31日,年龄18岁,至复旦大学附属中山医院就诊,经胃镜检查确诊存在GOV且曾有过出血的肝硬化患者。通过随访再出血、治疗转变和生存情况,评估预后变化及其预后影响因素。结果共纳入患者558例,2004年1月1日至2010年12月31日共235例,2011年1月1日至2013年12月31日共323例。年龄18～84岁,中位年龄55岁,男364例(65.2%)。Child评分中位数为7分(5～13分)。肝硬化常见病因乙肝230例(57.9%),乙肝肝硬化发生率从2004-2010年的63.8%下降到2011-2013年的53.6%。在2004-2010年行单纯食管静脉曲张套扎治疗182例(77.4%),食管套扎联合胃组织黏合剂治疗28例(11.9%)。2011-2013年行食管套扎联合胃组织黏合剂治疗194例(60.1%),单纯食管静脉曲张套扎治疗90例(27.9%)。共62例患者发生了治疗转换,脾切除联合断流的患者从87.9%逐渐减少至62.1%。两个时间段累积未再出血率比较,差异有统计学意义(P=0.010)。两组的累积生存率比较,差异有统计学意义(P0.001)。两个时间段治疗无效者分别为78例(33.2%)和77例(23.8%)(P=0.015)。结论随着以食管套扎为主逐渐转变为联合食管套扎与胃组织黏合剂治疗为主的内镜治疗方式的转变,内镜治疗GOV患者的预后得到了显著改善。     

肝硬化门静脉高压食管胃静脉曲张出血的临床特点及防治研究

［摘要］　目的　探讨肝硬化门静脉高压患者食管胃静脉曲张（GOV）出血的临床特点及防治。方法　本研究纳入临床资料完整的330例住院肝硬化患者,其中肝硬化门静脉高压非GOV出血患者138例,首次出现GOV出血患者105例,GOV再出血患者87例。回顾性分析肝硬化门静脉高压GOV出血的临床特点,并以肝硬化非GOV出血组为对照,采用logistic回归分析GOV首次出血的危险因素。结果　330例肝硬化患者中,192例肝硬化并发GOV出血,一级预防管理中,既往接受一级预防患者21例(10.93%),其中接受非选择性β受体阻滞剂（NSBB）药物治疗6例（3.13%）,经内镜治疗15例（7.81%）;二级预防管理中,既往接受二级预防患者125例(65.10%),其中经NSBB药物治疗18例（9.38%）,内镜治疗69例（35.94%）,介入治疗56例（29.17%）。Child-Pugh分级（OR=1.651,95%CI：1.115～2.444,P=0.012）、感染（OR=2.062,95%CI：1.055～4.032,P=0.034）。结论　Child-Pugh分级、感染是肝硬化门静脉高压GOV出血发生的独立危险因素。对于肝硬化门静脉高压患者GOV出血一级预防、二级预防及治疗存在不足,需要加大高危人群的筛查、提高首次及再次出血的预防。     

30岁以下人群食管胃静脉曲张患者临床特点分析

目的 分析总结30岁以下食管胃静脉曲张(GOV)患者的临床特点。方法 2015年1月～2020年12月解放军总医院第一医学中心消化内科医学部收治的61例30岁以下GOV患者,提取、分析和总结其临床资料。结果 在61例GOV患者中,肝硬化门静脉高压症27例(44.3%),其中隐源性肝硬化占40.7%,乙型肝炎肝硬化占33.3%,和非肝硬化性门静脉高压(NCPH)34例(55.7%),其中以门静脉海绵样变占61.8%;基于内镜下静脉曲张LDRf分型,在位置方面主要以Le/g型多见(77.1%),在直径方面,D1.0占41.0%,在出血风险方面,Rf1分级占77.1%;针对GOV治疗,以二级预防治疗为主(85.7%),多采用组织胶或硬化剂注射或套扎联合治疗(66.1%);NCPH患者GOV再出血比例为11.8%,显著低于肝硬化组的29.6%(P＜0.01)。结论 30岁以下人群GOV患者以NCPH居多,其中以各种原因引起的门脉海绵样变最多见。NCPH患者并发GOV经内镜治疗后再出血发生率显著低于肝硬化患者。     

食管胃静脉曲张早期再出血的危险因素分析

食管胃静脉曲张(gastroesophageal varices,GOV)破裂出血是临床急危重症,病死率高,其最常见的病因为肝硬化门静脉高压.尽管药物及内镜下治疗能使大部分患者得到满意的止血效果,但仍存在复发的风险.根据出血控制后再次出血的时间长短,分为早期再出血(出血控制后72 h～6周内)及迟发性再出血(出血控制6周后)[1].如何识别高风险因素,预防早期再出血是临床医师面临的难题.本文对我院2007年1月至2009年12月收治的140例患者,共154例次内镜下治疗的GOV进行分析,探讨早期再出血的危险因素.     

乙型肝炎肝硬化并发食管胃底静脉曲张破裂出血患者临床特征及其危险因素分析*

目的 分析乙型肝炎肝硬化并发食管胃底静脉曲张破裂出血(EVB)患者的临床特征,并探讨乙型肝炎肝硬化发生EVB的危险因素。方法 2018年6月～2020年6月我院收治的乙型肝炎肝硬化并发食管胃底静脉曲张(GOV)患者108例,当发生曲张静脉破裂出血时,给予内科止血治疗。收集临床资料,应用单因素和多因素Logistic回归模型分析确定乙型肝炎肝硬化发生EVB的独立危险因素。结果 在108例乙型肝炎肝硬化并发GOV患者中,38例(35.2%)发生EVB,其中5例(13.2%)患者在发病72 h内死亡;单因素分析提示过度劳累与GOV患者发生EVB无显著的相关性(P>0.05),而饮食不当、服用非甾体类抗炎药、血小板计数(PLT)、凝血酶原时间(PT)、血清白蛋白(ALB)、门静脉内径、脾静脉内径、红色征、肝功能Child-Pugh分级和食管胃底静脉曲张程度与GOV患者发生EVB显著相关(P<0.05);多因素Logistic回归分析结果显示饮食不当【OR(95% CI)为2.2(1.3～3.7)】、门静脉内径增宽【OR(95% CI)为1.4(1.1～1.7)】、PT延长【OR(95% CI)为1.3(1.1～1.6)】、有红色征【OR(95% CI)为3.3(1.6～7.1)】、肝功能Child-Pugh C级【OR(95% CI)为3.9(1.7～9.0)】和重度食管胃底静脉曲张【OR(95% CI)为3.5(1.9～6.5)】是乙型肝炎肝硬化发生EVB的独立危险因素。结论 乙型肝炎肝硬化并发GOV患者存在一些上消化道出血的原因,其中EVB是重要的致命原因。EVB发生的本身有一些危险因素,需要临床给予必要的一级和二级预防措施,以减少EVB的发生。     

门静脉右支流速对肝硬化诊断价值比较研究

目的探讨超声检查中门静脉右支流速预测肝硬化发生的诊断价值。方法对452例慢性肝病患者行超声检查,记录脾脏长度、脾脏厚度、门静脉宽度、门静脉右支流速值,并绘制相应的受试者工作特征曲线(ROC),计算曲线下面积(AUC),依据不同肝硬化程度进行分层分析。结果门静脉右支流速诊断肝硬化的AUC为0.720(可信区间为0.655~0.698),根据ROC曲线选定的最佳分界点(cut-off)值为15.3 kPa(P0.0001)。灵敏度为73.08%,特异度为69%,约登指数0.36。结论门静脉右支流速对预测肝硬化发生具有较高的诊断价值,随着肝硬化程度加重,门静脉右支流速随之降低。     

基于诺模图模型预测内镜下治疗肝硬化胃静脉曲张的疗效

目的通过诺模图(Nomogram)模型预测内镜下组织黏合剂治疗肝硬化患者胃静脉曲张的疗效。方法选择2014年8月至2017年9月因肝硬化食管胃底静脉曲张破裂出血至复旦大学附属中山医院就诊且接受内镜下组织黏合剂治疗的158例患者。随访12个月,主要结局指标为再出血。分析肝硬化胃静脉曲张内镜下治疗后再出血的影响因素。构建诺模图模型,比较其与Child分级、计算机体层摄影血管造影(CTA)和肝静脉压力梯度(HVPG)预测肝硬化胃静脉曲张内镜下治疗后再出血的准确性。统计学分析采用单因素和多因素Cox回归分析,以及Kaplan-Meier曲线和log-rank检验。结果随访中,在内镜下治疗后2、6和12个月分别出现再出血18例(11.4%)、37例(23.4%)和49例(31.0%)。单因素Cox回归分析结果显示,性别、酒精性肝硬化、糖尿病、Child-Pugh分级(A级与B或C级)、CTA腔外血管(有与无)、HVPG(<16 mmHg与≥16 mmHg,1 mmHg=0.133 kPa)、门脉系统广泛栓塞、食管静脉曲张、食管胃静脉曲张2型、组织黏合剂注射点(≤3点与>3点)和组织黏合剂注射量(≤3 mL与>3 mL)均为胃静脉曲张内镜下治疗后再出血的影响因素(HR=0.575、2.018、1.562、3.433、2.945、1.859、2.743、0.324、1.840、1.477、1.716,95%CI 0.305~1.084、0.902~4.514、0.814~2.792、1.753~6.724、1.663~5.217、1.012~3.415、0.852~8.830、0.079~1.335、1.012~3.317、0.839~2.602、0.935~3.152,P均<0.2)。多因素Cox回归分析结果显示,Child-Pugh分级、CTA腔外血管和HVPG均为胃静脉曲张内镜下治疗后再出血的独立危险因素(HR=2.665、2.886、2.095,95%CI 1.339~5.300、1.580~5.271、1.099~3.995,P均<0.05)。Kaplan-Meier曲线显示,Child-Pugh分级(A级与B或C级)、CTA腔外血管(有与无)和HVPG(<16 mmHg与≥16 mmHg)均能有效预测胃静脉曲张内镜下治疗后1年累积未再出血率,差异均有统计学意义(P均<0.05)。ROC曲线分析显示,联合Child-Pugh分级、CTA腔外血管和HVPG(<16 mmHg与≥16 mmHg)的模型可能比Child-Pugh分级和HVPG有更好的预测价值(AUC=0.746、0.673和0.585,95%CI 0.662~0.829、0.583~0.762和0.486~0.683,P<0.01、P=0.001、P=0.089)。根据诺模图评分的下四分位数和上四分位数将患者分为低、中、高危组,结果显示诺模图可以有效区分胃静脉曲张内镜下治疗后再出血的高危人群,差异有统计学意义(P<0.01)。结论CTA腔外血管、HVPG和Child-Pugh分级是肝硬化胃静脉曲张内镜下治疗疗效的独立预测指标,基于此3项指标建立的诺模图模型的预测准确性可能优于Child-Pugh分级和HVPG。     

肝硬化食管胃底静脉曲张破裂出血患者血清中胰岛素样生长因子结合蛋白-3的水平变化及临床意义

目的探究胰岛素样生长因子结合蛋白-3(IGFBP-3)在肝硬化食管胃底静脉曲张破裂出血患者血清中的表达水平及临床意义。方法选择2017年2月至2018年6月在苏州市中西医结合医院就诊的242例肝硬化食管胃底静脉曲张破裂出血患者作为研究对象。根据治疗后是否发生再出血将患者分为未出血组(n=160)和再出血组(n=82)。采用ELISA法检测患者血清IGFBP-3的表达水平,并分析其与患者发生再出血的关系。结果再出血组血清IGFBP-3的表达水平高于未出血组,两组差异有统计学意义(P0.05)。多因素logistic回归分析结果显示,Child-Pugh分级为C级、门静脉内径、白细胞计数和IGFBP-3是肝硬化食管胃底静脉曲张破裂出血后发生再出血的独立危险因素(P均0.05),血钠是肝硬化食管胃底静脉曲张破裂出血后发生再出血的独立保护因素(P0.05)。IGFBP-3预测肝硬化食管胃底静脉曲张破裂出血后发生再出血的ROC曲线下面积(AUC)、敏感度和特异度分别为0.894、97.56%和70.00%。构建预测肝硬化食管胃底静脉曲张破裂出血后发生再出血的logistic回归模型(由Child-Pugh分级、门静脉内径、白细胞计数、血钠和IGFBP-3组成)列线图,其拟合曲线与理想曲线的重合度较高,一致性指数(C指数)为0.962。结论 IGFBP-3在肝硬化食管胃底静脉曲张破裂出血患者血清中的表达水平越高,提示患者发生再出血的风险越高。由Child-Pugh分级、门静脉内径、白细胞计数、血钠和IGFBP-3构建的logistic回归模型列线图可以有效评估肝硬化食管胃底静脉曲张破裂出血后发生再出血的风险。     

肝硬化重度食管胃静脉曲张治疗后再出血及5年预后影响因素分析

目的探讨肝硬化并发重度食管胃静脉曲张破裂出血(EVB)患者5年内再出血的危险因素及影响其5年生存的相关因素。方法回顾性选取2012年5月—2014年5月因重度首次EVB于天津市第三中心医院就诊的肝硬化129例患者,随访时间为5年。分析患者年龄、性别、肝硬化原因、首次出血时是否合并感染、肝硬度(LSM)、脾硬度(SSM)、门静脉内径、生化学指标、再出血时间及预后等临床资料。以食管胃静脉曲张再出血为主要研究终点,以死亡为次要研究终点。计量资料2组间比较采用t检验;计数资料2组间比较采用χ~2检验;分别采用logistic回归分析法和Cox回归分析法筛选出EVB患者治疗后再次出血的独立危险因素及5年的生存预测指标,Kaplan-Meier曲线分析累积未再出血率。结果 129例患者中有87例(67.4%)患者在随访期间发生再出血。再出血组与未再出血组患者比较,酒精性肝硬化患者比例(χ~2=4.896,P=0.027)、门静脉内径(t=2.203,P=0.030)、LSM(Z=-2.771,P=0.006)和SSM(t=2.678,P=0.010)差异均有统计学意义。酒精性肝硬化患者的平均出血次数和累计出血率显著高于非酒精性肝硬化患者(P值均0.05)。多因素logistic回归分析显示酒精性肝硬化、LSM和SSM是EVB患者治疗后5年内再出血的独立危险因素(OR值分别为5.687、1.039、1.078,95%CI分别为1.230～26.129、1.010～1.070、1.028～1.129,P值分别为0.025、0.007、0.001)。129例患者中死亡45例(34.9%)。Cox单因素分析显示,死亡组与存活组在年龄、出血次数、平均动脉压、门静脉内径、AST、淋巴细胞百分比以及首次出血是否感染等均存在明显差异(P值均0.05)。进一步多因素分析表明,患者5年生存率与门静脉内径、年龄、出血次数以及首次出血时是否感染有关(OR值分别为1.459、1.053、1.286、5.239,95%CI分别为1.056～2.014、1.006～1.103、1.040～1.591、1.750～15.641,P值分别为0.022、0.026、0.020、0.003)。结论酒精性肝硬化、LSM和SSM是影响EVB患者5年内发生再出血的独立危险因素,而年龄、出血次数、门静脉内径以及首次出血时是否合并感染与5年预后有关。     

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.     

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.     

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.