Neuroendocrine,epigenetic, and intergenerational effects of general anesthetics

The progress of modern medicine would be impossible without the use of general anesthetics (GAs). Despite advancements in refining anesthesia approaches, the effects of GAs are not fully reversible upon GA withdrawal. Neurocognitive deficiencies attributed to GA exposure may persist in neonates or endure for weeks to years in the elderly. Human studies on the mechanisms of the long-term adverse effects of GAs are needed to improve the safety of general anesthesia but they are hampered not only by ethical limitations specific to human research, but also by a lack of specific biological markers that can be used in human studies to safely and objectively study such effects. The latter can primarily be attributed to an insufficient understanding of the full range of the biological effects induced by GAs and the molecular mechanisms mediating such effects even in rodents, which are far more extensively studied than any other species. Our most recent experimental findings in rodents suggest that GAs may adversely affect many more people than is currently anticipated. Specifically, we have shown that anesthesia with the commonly used GA sevoflurane induces in exposed animals not only neuroendocrine abnormalities (somatic effects), but also epigenetic reprogramming of germ cells (germ cell effects). The latter may pass the neurobehavioral effects of parental sevoflurane exposure to the offspring, who may be affected even at levels of anesthesia that are not harmful to the exposed parents. The large number of patients who require general anesthesia, the even larger number of their future unexposed offspring whose health may be affected, and a growing number of neurodevelopmental disorders of unknown etiology underscore the translational importance of investigating the intergenerational effects of GAs. In this mini review, we discuss emerging experimental findings on neuroendocrine, epigenetic, and intergenerational effects of GAs.     

Discrimination of idiopathic pain syndromes from neurogenic pain syndromes and healthy volunteers by means of clinical rating,personality traits,monoamine metabolites in CSF,serum cortisol,platelet MAO and urinary melatonin

Summary The aim of the present study was to investigate the discriminative power of a series of variables (including determination of depressive symptomatology by means of a visual analogue scale, determination of personality traits by means of the Karolinska Scales of Personality, determination of monoamine metabolites in CSF, platelet MAO activities, serum cortisol before and after dexamethasone suppression and urinary melatonin) in differentiating (a) chronic pain patients from healthy subjects, and (b) patients with idiopathic pain syndromes from patients with neurogenic pain syndromes. Separately each of the measures gave a significant but often low contribution to the discrimination, while a combination of several measures gave a complete discrimination both between healthy subjects and patients with chronic pain syndromes and between patients with idiopathic and neurogenic pain syndromes, respectively.Supported in part by grants from the Swedish Medical Research Council (grants no. 3371, 4145 and 5740) and by a grant from Stiftelsen Söderström-Königska Sjukhemmet     

米非司酮试验在库欣综合征诊断上的应用

应用一次法口服４ｍｇ／ｋｇ的米非司酮（ＲＵ４８６）观察１７例单纯性肥胖和７例疑似库欣组的病人服药前后的反应，并与１０例正常人以及２９例库欣综合征病人进行比较，发现库欣综合征病人服药以后，血Ｆ２４小时尿Ｆ及血ＡＣＴＨ均无显著性变化（Ｐ〉０．０５），而其他三组各指标均升高（Ｐ〈０．０１）。并得出鉴别库欣综合征与非库欣综合征的标准为：血Ｆ增加的百分比为３０％２４小时尿Ｆ增加百分比为１８％，ＡＣＴＨ增加百     

The effects of running and meditation on beta-endorphin, corticotropin-releasing hormone and cortisol in plasma, and on mood

The relations between three hormones of the hypothalamic-pituitary-adrenocortical (HPA) axis, beta-endorphin (β-EP), corticotropin-releasing hormone (CRH) and cortisol, and mood change were examined in 11 elite runners and 12 highly trained meditators matched in age, sex, and personality. Despite metabolic differences between running and meditation, we predicted that mood change after these activities would be similar when associated with similar hormonal change. Compared to pre-test and control values, mood was elevated after both activities but not significantly different between the two groups at post-test. There were significant elevations of β-EP and CRH after running and of CRH after meditation, but no significant differences in CRH increases between groups. CRH was correlated with positive mood changes after running and meditation. Cortisol levels were generally high but erratic in both groups. We conclude that positive affect is associated with plasma CRH immunoreactivity which itself is significantly associated with circulating β-EP supporting a role for CRH in the release of β-EP. Increased CRH immunoreactivity following meditation indicates, however, that physical exercise is not an essential requirement for CRH release.     

Flumazenil exerts intrinsic activity on sleep EEG and nocturnal hormone secretion in normal controls

The physiological function of benzodiazepine (BDZ) receptors includes regulation of sleep and neuroendocrine activity. Most of the pharmacological effects of BDZ are blocked by flumazenil. However, recent neurological and behavioral studies suggest that flumazenil has its own central intrinsic activity. This issue was addressed in a study of the sleep EEG and the nocturnal secretion of growth hormone and cortisol in ten normal male controls, who were given flumazenil either alone or in combination with the BDZ agonist midazolam, placebo and midazolam alone. Flumazenil prompted an increase in sleep onset latency, a decrease in slow wave sleep and an increase in wakefulness. Plasma cortisol concentrations after flumazenil administration were lower than after midazolam. Both flumazenil and midazolam decreased nocturnal growth hormone secretion. After simultaneous application of both BDZ receptor ligands the growth hormone blunting was amplified. Our study demonstrates that at the level of the sleep EEG and neuroendocrine activity flumazenil is capable of exerting both agonistic and inverse agonistic or antagonistic effects.Parts of this study were presented at the 69th Meeting of the Deutsche Physiologische Gesellschaft, Freiburg, 6–8 March, 1991     

汤岗子矿泉浴对大鼠血液皮质醇及甲状腺素日生物周期节律影响的实验观察

本文报告大鼠分别在6时、12时、18时、24时接受汤岗子矿泉38～39℃浸浴15分钟后,立即断头取血测定血液皮质醇及甲状腺素(T_4)。在6时、24时的矿泉浸浴组大鼠血浆皮质醇比对照组明显升高。在12时、18时矿泉浸浴组大鼠血清T_4比对照组明显升高。说明肾上腺皮质及甲状腺功能对全身矿泉浸浴热刺激的反应也遵循日周期节律。为矿泉治疗的时间生物学理论提供依据。     

抑郁患者血清皮质醇与血压在应激前后的变化

目的研究抑郁患者血清皮质醇浓度、血压在应激前后的变化以及它们之间的关系。方法分别在安静状态、心理应激状态和心理应激后 (恢复状态 )测量抑郁组和对照组的血清皮质醇浓度、血压 ,比较两组上述指标的差异 ,以及心理应激前后的变化。心理应激以规定时间内的计算试验模拟 ,血清皮质醇以酶联免疫试验检测 ,血压为常规检测。结果 1.皮质醇 :抑郁组在安静状态、应激状态、恢复状态的皮质醇浓度显著高于对照组 (P <0 .0 5 ) ,抑郁组应激前后皮质醇浓度的波动显著小于对照组 (P <0 .0 5 )。2 .收缩压 :安静状态和恢复状态时抑郁组的收缩压显著高于对照组 (P <0 .0 5 ) ,应激状态时两组无统计学差异 ;应激前后收缩压的波动两组无统计学差异。 3 .舒张压 :抑郁组在安静状态时舒张压显著高于对照组(P <0 .0 5 ) ,在应激状态和恢复状态时两组无统计学差异 ;应激前后舒张压的波动两组无统计学差异。结论抑郁患者存在基础血压升高 ,此现象可能与抑郁患者血清皮质醇浓度升高有关。     

The relations among putative biorisk markers in schizotypal adolescents: minor physical anomalies, movement abnormalities, and salivary cortisol.

BACKGROUND: Evidence suggests that prenatal insult may play a role in the etiology of psychotic disorders. Minor physical anomalies (MPA) are an indicator of abnormal fetal development and are elevated in individuals at genetic and behavioral risk for psychosis. Yet, there has been little empirical research on the relationships between MPAs and other neurobiological risk indicators. We hypothesized that the frequency of MPAs (an external marker of prenatal central nervous system [CNS] disruption) would be associated with two other biomarkers suggestive of disruptions in fetal neurodevelopment: movement abnormalities (an indicator of striatal abnormalities) and heightened cortisol secretion (an indicator of hypothalamic-pituitary-adrenal [HPA]/hippocampal function). METHODS: Participants with schizotypal personality disorder (SPD; n = 39) and both normal (n = 47) and other personality disorders (n = 28) control subjects were administered structured diagnostic interviews and assessed for MPAs, movement abnormalities, and salivary cortisol. RESULTS: Schizotypal personality disorder participants showed significantly greater MPAs and movement abnormalities and higher cortisol than both the normal and other personality disorders groups. Hierarchical linear regression analyses revealed that higher rates of MPAs were linked with greater movement abnormalities and salivary cortisol. CONCLUSIONS: The findings suggest that MPAs serve as a marker of neurodevelopmental abnormalities that affect striatal and hippocampal regions.     

危重新生儿血糖、胰岛素及皮质醇的初步研究

本文通过对３８例危重新生儿血糖、胰岛素及皮质醇的研究，发现在危重新生儿组血糖与皮质醇的均植高于对照组（分别为Ｐ＜０．０５与Ｐ＜０．０１），且危重新生儿组高血糖的发生率（３４．２％）也明显高于对照组（６％），而血胰岛素在各组之间无显著差异（Ｐ＞０．０５），研究表明危重新生儿易发生高血糖，其发生的机理与血皮质醇的升高及新生儿胰β细胞功能不良有关。     

Aldosterone and its mechanism of action: more questions than answers

The physiology of the steroid hormone, aldosterone is well defined. The molecular events that mediate this response remain to be elucidated. Aldosterone binds to a specific mineralocorticoid receptor (MR) in sodium transporting epithelia. The structural determinants of ligand-binding have been explored through the analysis of steroid resistance syndromes, however, the molecular basis of resistance to aldosterone, pseudo-hypoaldosteronism remains an enigma. Cortisol also binds MR, access is however restricted by the enzyme 11β-hydroxysteroid dehydrogenase. The MR induces specific genes which regulate apical amiloride-sensitive epithelial sodium channels; the finding of activating mutations in Liddles syndrome (pseudoaldosteronism) has emphasised their key role. Such mechanisms may apply not only to the peripheral effects of aldosterone but also to the central regulation of blood pressure.