健康女童和特发性中枢性性早熟女童血清硫酸脱氢表雄酮的变化

分别测定198例健康女童和152例特发性中枢性性早熟(ICPP)女童血清硫酸脱氢表雄酮(DHEA-S).健康女童血清DHEA-S随年龄增长和Tanner分期进展而增高(r分别为0.71和0.67,均P＜0.01),ICPP女童血清DHEA-S高于同龄健康女童,但接近相同Tanner分期的健康女童.提示肾上腺功能初现和性腺功能初现之间有密切联系.     

女童特发性中枢性性早熟及正常女性青春发育各期血浆kisspeptin水平研究

目的 研究女童特发性中枢性性早熟(ICPP)及正常女性青春发育各期血浆kisspeptin水平,并探讨以此鉴别ICPP和单纯性乳房早发育(premature thelarche,PT)的意义.方法 女童共92名,女青年18名,其中ICPP 10例、PT12例、正常青春发育Tanner Ⅰ～Ⅴ期各16～19名.采用酶联免疫吸附方法(ELISA)检测血浆kisspeptin.结果 血浆kisspeptin水平ICPP组明显高于PT组[(1.73±0.23对1.43±0.29)ng/ml,P＜0.05];正常青春发育kisspeptin水平从Tanner Ⅱ期至Tanner Ⅴ期逐渐下降,其中以Tanner Ⅱ期最高;Tanner Ⅳ、Ⅴ期明显低于TannerⅠ、Ⅲ期(P＜0.01).结论 正常女性青春发育期血浆kisspeptin 水平以TannerⅡ期最高,检测其水平对于临床鉴别ICPP与PT有一定意义.

Abstract：

Objective To investigate the pattern of plasma kisspeptin levels in normal female during various pubertal Tanner stages and the girls with idiopathic central precocious puberty(ICPP) or with premature thelarche(PT), and to evaluate the significance of detecting plasma kisspeptin levels as a new criterion for early differentiation between ICPP and PT.Methods Each study group of normal pubertal females with Tanner stage Ⅰ to Ⅴ comprised 16 to 19 individuals.The levels of plasma kisspeptin were also detected in girls with ICPP(n= 10)or PT(n = 12).The plasma kisspeptin levels were detected by enzyme-linked immunosorbent assay (ELISA).Results The level of kisspeptin was significantly higher in ICPP group than in that of PT group [(1.73±0.23 vs1.43±0.29) ng/ml, P＜0.05].Among the normal pubertal females, the level of kisspeptin decreased gradually from Tanner stage Ⅱ to Tanner stage Ⅴ, being highest in Tanner stage Ⅱ [(1.73±0.22) ag/ml] ,lower in stage Ⅳ and Ⅴ than in stage Ⅰ and Ⅲ (P＜0.01).Conclusions Plasma kisspeptin level was the highest during Tanner stage Ⅱ in normal female pubertal development.It is significant to detect plasma kisspeptin level for the differential diagnosis of ICPP and PT.     

GnRHa治疗对中枢性性早熟女孩线性生长和成年身高的影响

对82例中枢性性早熟(CPP)女童使用促性腺激素释放激素类似物(GnRHa)治疗后线性生长及终身高进行评价.治疗两年以上患者的第2年生长速度与其治疗第2年和第1年的骨龄差值呈正相关(P<0.01).治疗后按骨龄的身高标准差分值增大,预测成人身高提高.随访26例达终身高患者,平均靶身高高于遗传靶身高.故适量的GnRHa治疗辅以有氧运动能够有效地改善CPP女童生长速度及终身高.     

GnRHa治疗对特发性中枢性性早熟女童肾上腺功能初现的影响

目的 通过随访特发性中枢性性早熟(ICPP)女童经促性腺激素释放激素类似物(GnRHa)治疗前、后阴毛发育情况和血硫酸脱氧表雄酮(DHEAS)水平,探讨肾上腺功能初现与性腺轴发育的关系.方法 对确诊为ICPP且按年龄判断血DHEAS的z分值超过正常上限(+2 s)的49例女童在GnRHa治疗前后每3-6个月行性征检查,治疗后每年检测血DHEAS.平均随访(4.08+0.83)年,其中16例随访至停药后1年.结果 治疗前阴毛发育2期(PH2)和阴毛发育3期(PH3)的达到年龄均小于正常[(8.07对11.16)岁,(8.82对12.40)岁],ICPP女童GnRHa受治期间阴毛发育进程显著慢于正常对照[PH2-PH3:(1.69对0.83)年;PH3-阴毛发育4期(PH4):(1.64对0.60)年];同时也长于治疗前的自然进程[PH2-PH3:(1.69对0.88)年].乳房开始发育至阴毛萌出的间期亦然,ICPP治疗前后和正常对照分别为1.13、3.62和0.76年.在GnRHa治疗期间ICPP女童每年DHEAS Z分值呈逐年递减,停药后又显增.结论 大于6岁的性腺轴初现提前可诱致肾上腺功能初现提前,而GnRHa治疗在抑制性腺轴的同时也能延缓肾上腺功能发育的进程.     

GnRHa治疗对特发性中枢性性早熟女童肾上腺功能初现的影响

目的 通过随访特发性中枢性性早熟(ICPP)女童经促性腺激素释放激素类似物(GnRHa)治疗前、后阴毛发育情况和血硫酸脱氧表雄酮(DHEAS)水平,探讨肾上腺功能初现与性腺轴发育的关系.方法 对确诊为ICPP且按年龄判断血DHEAS的z分值超过正常上限(+2 s)的49例女童在GnRHa治疗前后每3-6个月行性征检查,治疗后每年检测血DHEAS.平均随访(4.08+0.83)年,其中16例随访至停药后1年.结果 治疗前阴毛发育2期(PH2)和阴毛发育3期(PH3)的达到年龄均小于正常[(8.07对11.16)岁,(8.82对12.40)岁],ICPP女童GnRHa受治期间阴毛发育进程显著慢于正常对照[PH2-PH3:(1.69对0.83)年;PH3-阴毛发育4期(PH4):(1.64对0.60)年];同时也长于治疗前的自然进程[PH2-PH3:(1.69对0.88)年].乳房开始发育至阴毛萌出的间期亦然,ICPP治疗前后和正常对照分别为1.13、3.62和0.76年.在GnRHa治疗期间ICPP女童每年DHEAS Z分值呈逐年递减,停药后又显增.结论 大于6岁的性腺轴初现提前可诱致肾上腺功能初现提前,而GnRHa治疗在抑制性腺轴的同时也能延缓肾上腺功能发育的进程.     

GnRHa治疗对中枢性性早熟女孩线性生长和成年身高的影响

对82例中枢性性早熟(CPP)女童使用促性腺激素释放激素类似物(GnRHa)治疗后线性生长及终身高进行评价.治疗两年以上患者的第2年生长速度与其治疗第2年和第1年的骨龄差值呈正相关(P<0.01).治疗后按骨龄的身高标准差分值增大,预测成人身高提高.随访26例达终身高患者,平均靶身高高于遗传靶身高.故适量的GnRHa治疗辅以有氧运动能够有效地改善CPP女童生长速度及终身高.     

GnRHa治疗对中枢性性早熟女孩线性生长和成年身高的影响

对82例中枢性性早熟(CPP)女童使用促性腺激素释放激素类似物(GnRHa)治疗后线性生长及终身高进行评价.治疗两年以上患者的第2年生长速度与其治疗第2年和第1年的骨龄差值呈正相关(P<0.01).治疗后按骨龄的身高标准差分值增大,预测成人身高提高.随访26例达终身高患者,平均靶身高高于遗传靶身高.故适量的GnRHa治疗辅以有氧运动能够有效地改善CPP女童生长速度及终身高.     

GnRHa治疗对中枢性性早熟女孩线性生长和成年身高的影响

对82例中枢性性早熟(CPP)女童使用促性腺激素释放激素类似物(GnRHa)治疗后线性生长及终身高进行评价.治疗两年以上患者的第2年生长速度与其治疗第2年和第1年的骨龄差值呈正相关(P<0.01).治疗后按骨龄的身高标准差分值增大,预测成人身高提高.随访26例达终身高患者,平均靶身高高于遗传靶身高.故适量的GnRHa治疗辅以有氧运动能够有效地改善CPP女童生长速度及终身高.     

GnRHa治疗对中枢性性早熟女孩线性生长和成年身高的影响

对82例中枢性性早熟(CPP)女童使用促性腺激素释放激素类似物(GnRHa)治疗后线性生长及终身高进行评价.治疗两年以上患者的第2年生长速度与其治疗第2年和第1年的骨龄差值呈正相关(P<0.01).治疗后按骨龄的身高标准差分值增大,预测成人身高提高.随访26例达终身高患者,平均靶身高高于遗传靶身高.故适量的GnRHa治疗辅以有氧运动能够有效地改善CPP女童生长速度及终身高.     

基因重组人生长激素对GnRHa治疗中生长减速的特发性中枢性性早熟患儿身高的影响

目的观察联合应用基因重组人生长激素（rhGH）对促性腺激素释放激素类似物（GnRHa）治疗中生长减速的特发性中枢性性早熟（CCP）患儿身高的影响。方法将确诊为CCP伴生长减速的患儿30例分为两组,A组15例予GnRHa联合rhGH治疗,B组15例为对照组仅予GnRHa治疗。观察骨龄、年生长速率（GV）、体质量、身高、骨龄身高、成年预测身高（PAH）、血脂、血糖、胰岛素、甲状腺功能、血清胰岛素样生长因子-1（IGF-1）、乳房及子宫卵巢B超等指标,观察时间为6个月。结果治疗6个月后A组患儿的GV、实际身高、PAH和IGF-1水平均较治疗前和B组治疗后明显增加（P〈0．05）,其他指标两组治疗前后未见明显差异。结论GnRHa联合rhGH治疗能在不加速骨龄的情况下有效提高生长速率,有望改善GnRHa治疗中生长减速的CCP患儿的PAH。     

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.     

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.     

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.     

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.     

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.