生物熵在医学研究中的应用

从熵的角度解释生命体状态变化的物理本质,生命体的各系统在不同的状态下,都对应着一定的熵值。疾病状态时,体内微生态平衡发生变化,相应的熵值也就发生改变。     

熵指数监测在胆囊手术中的应用

目的观察全身麻醉下胆囊切除手术应用七氟醚复合舒芬太尼、丙泊酚麻醉中熵指数—反应熵和状态熵的变化。方法ASAⅠ～Ⅱ级,择期行胆囊切除手术的患者30例。麻醉诱导:丙泊酚2～2.5 mg/kg,舒芬太尼0.3μg/kg,罗库溴铵0.8 mg/kg。麻醉维持:七氟醚吸入,维持在2.0%～3.5%的有效浓度,必要时追加丙泊酚。麻醉全程中监测熵指数,记录诱导前(基础值)、诱导即刻、气管插管即刻、切皮即刻、牵拉胆囊、胆囊切除、恢复期吸痰及拔管各时间点所对应的状态熵、反应熵、收缩压、舒张压和心率的值。结果状态熵的基础值低于反应熵,诱导后状态熵、反应熵均显著下降,恢复期明显回升,但未能回到基础值。结论熵指数能够及时反映麻醉期间患者意识水平变化,也能反映插管、拔管的最佳时机。     

ICU患者的心理反应及护理干预措施探讨

目的 探讨心理护理对ICU患者康复的作用.方法 针对ICU患者常见的不良心理状态,采取相应的护理对策.结果 ICU患者在经过有针对性的心理护理后,心理障碍逐渐消除,情绪稳定,能够积极配合治疗和护理,促进了疾病早日康复.结论 良好的心理状态能够增强患者战胜疾病的信心,提高机体的抗病能力,因此做好ICU患者的心理护理可以促进机体早日康复.     

肾小球疾病的凝血象(附74例报告)

近年来很多研究均提示凝血过程的变化对肾小球疾病的发生、发展具有十分重要的影响。为进一步了解发生肾小球疾病时机体的凝血状态,我们观察了74例肾小球疾病的凝血象,现将结果报告如下。     

关于亚健康状态的问答

什么是亚健康状态? 答:亚健康状态是近年来医学界提出的一个新概念,一般指机体无明显疾病却呈现出活力降低,适应能力呈不同程度减退的一种生理状态,是由于机体各系统的生理功能低下所致,是介于健康与疾病之间的一种生理功能低下的状态.     

妊娠高血压疾病孕妇围生期凝血系统指标及血小板活化状态的变化探究

<正>妊娠高血压疾病是导致孕产妇死亡的重要原因,而围生期是产妇机体多系统状态负荷较重的阶段,也是相对危险的阶段,因此围生期机体的变化波动状态研究有助于干预措施的制定。妊娠高血压疾病作为循环系统疾病,凝血系统的变化明显,同时血小板活化状态也是血流状态的重要影响因素~([1]),上述血液指标在妊娠高血压疾病孕妇中多呈现高表达状态,     

肝功能不全患者的临床用药

在临床疾病的治疗过程中,患者有时不仅患有某种药物所治疗的疾病,还常常同时伴有肝脏疾病,肝功能不良。肝脏器质性病变会造成患者机体内环境和各系统脏器功能失调,一方面会使机体对药物的吸收、分布、代谢、排泄等发生变化,导致药动学改变;另一方面会使某些组织器官的受体数目和功能发生变化,改变机体对相应药物的反应性,导致药效学改变。对这类患者的用药应当引起重视。     

烧伤患者夜间睡眠护理

<正>在疾病的治疗和修复过程中,患者机体所处的最佳状态是睡眠状态。若患者的睡眠发生异常或长期不能保证夜间睡眠,中枢神经系统和各组织器官的生理机能则得不到足够的休息而处于低能状态,降低机体的抵抗力和战胜疾病的能力,不利于机体的恢复。因此,患者夜间睡眠的护理不可忽视。     

肌松药对麻醉诱导意识消失期间熵指数的影响

目的 探讨肌松药对麻醉诱导意识消失期间熵指数的影响.方法 30例行腹腔镜胆囊切除术的患者,随机分为2组:试验组给予单次维库溴铵,而对照组给予生理盐水.全麻诱导:2组均接受了目标浓度的丙泊酚输注直到病人意识消失.意识消失后的2分钟,试验组给予单次维库溴铵0.1mg/kg,对照组给予生理盐水.记录脑电双频指数及状态熵和反应熵指数.结果 在意识消失时的两组间结果相似.病人意识消失后对照组用药后较意识消失时的脑电双频指数(P＜0.002),状态熵(P＜0.05),反应熵(P＜0.01)均下降.试验组在脑电双频指数(P＜0.0001),状态熵(P＜0.0001),反应熵(P＜0.0001)下降.试验组在双频指数(P＜0.05)和反应熵(P＜0.01)方面的下降较对照组显著.结论 浅麻醉病人给予肌松剂时双频指数和反应熵下降,而状态熵则变化不明显.     

幽门螺杆菌感染与自身免疫性疾病的关系研究进展

自身免疫性疾病（autoimmune disease）是机体对自身成分发生免疫应答而导致的疾病状态。人体对外来抗原免疫应答的结局通常是外来抗原的清除,如细菌毒素的清除。在对自身细胞或组织抗原发生免疫应答时,机体的免疫系统不能或不易清除自身的细胞或组织成分,而是持续不断地对其进行免疫攻击,结果引起自身免疫性疾病。     

Structural Relaxation of Acetaminophen Glass

Purpose The aim is to determine the structural stability of acetaminophen glass with time and temperature change, and to examine the merits of adapting the structural relaxation models of the glassy state for pharmaceuticals. Methods Differential scanning calorimetry technique has been used to study the acetaminophen glass after keeping the samples for various periods at fixed temperatures and after keeping at various temperatures for fixed periods. Results A general formalism for thermodynamic changes during storage in a temperature fluctuating environment is given and the kinetics of the enthalpy and entropy decrease determined. At a fixed temperature, the decrease occurs according to a non-exponential kinetics. For the same storage time, but at different temperatures, the enthalpy and entropy decrease rises to a maximum value at a certain temperature and then declines. The peak appears at the temperature at which the internally equilibrated state of the sample is reached for a fixed storage time. The change in the normalized heat capacity during the heating of acetaminophen has been analysed in terms of a non-exponential, non-linear enthalpy relaxation model. Conclusion A single set of parameters that fit the data for unannealed acetaminophen glass does not fit the calorimetric data for annealed glass. Since acetaminophen molecules form intermolecular hydrogen-bonds in the crystal state and likely to form such bonds more easily in the disordered state, effect of such bonds on structural relaxation is likely to be significant.     

生命过程与生物熵

利用耗散结构理论通过生物熵在生命过程的变化分析,建立了正常生命过程的生物熵变数学模型,并对模型的数值变化进行了分析,探讨了生命过程中负熵流与熵增的变化趋势以及原因。     

频谱熵用于神经外科围手术期意识水平监测的临床观察

目的:探讨频谱熵用于神经外科围手术期意识水平监测的临床效果.方法:选择神经外科择期手术患者66例,随机分为:对照组(Ⅰ组,30例)和观察组(Ⅱ组,36例),切割硬脑膜均采用频谱熵和血流动力学监测.对照组依据血流动力学监测指标的变化,调整意识水平;而观察组则根据切割硬脑膜频谱熵指数调节意识水平.记录2组麻醉诱导前、插管后3 min、切皮、切割硬脑膜和手术结束前10 min平均动脉压(MAP)、心率(HR)、状态熵(SE)和反应熵(RE)值,麻醉复苏各项指标及麻醉药剂量.结果:插管后3min、切皮、切割硬脑膜、手术结束前10min,观察组SE和RE值均高于对照组.差异有统计学意义(P＜0.05或P＜0.01);而对照组MAP和HR明显低于观察组,差异有统计学意义(P＜0.05或P＜0.01).观察组的麻醉复苏指标,包括自主呼吸、睁眼指令、拔管时间均较对照组显著缩短,且对照组麻醉剂用最高于观察组,差异有统计学意义(均P＜0.01).结论:频谱熵用于神经外科围手术期意识水平监测的临床效果优于血流动力学监测指标.     

Using entropies of reaction to predict changes in protein stability: tyrosine-67-phenylalanine variants of rat cytochrome c and yeast Iso-1 cytochromes c

Using the voltammetric method of square-wave voltammetry, a direct electrochemical examination was made of the wild type and Tyr67Phe mutant of both rat cytochrome c and yeast iso-1-cytochrome c. In addition to determining the equilibrium reduction potential (E0') for each cytochrome, the entropy of reaction, deltaS0'(Rxn)(deltaS0'(Rxn) = S0'(Red) - S0'(Ox)), for the reduction process was determined via the non-isothermal method. Having determined deltaS0'(Rxn) and E0', deltaH0' was calculated. For rat cytochrome c, it was found that deltaS0'(Rxn) = -43 J mol(-1) K(-1) for the wild type and -53 J mol(-1) K(-1) for the Tyr67Phe variant, with the deltaH0' for both the wild type and variant nearly identical, indicating that the changes in reduction potential and probably stability are due to changes in deltaS0'(Rxn). In contrast the measured deltaS0'(Rxn) for yeast iso-1-cytochrome c demonstrated significant changes in both entropic and enthalpic contributions in going from wild type to mutant cytochrome c. The entropy of reaction provides information regarding the relative degree of solvation, and very likely the degree of compactness, of the oxidized state versus the reduced state of the redox protein. A thermodynamic scheme and stability derivation are presented that show how the entropies of reaction of wild type versus variant cytochromes contribute to and predict changes in stability in going from oxidized to reduced protein. For yeast iso-1-cytochrome c, the thermodynamically predicted change in stability was very close to the experimentally observed value, based on previous differential scanning calorimetric stability measurements. While such data is not available for rat cytochrome c, consideration of the enormously increased local stability of the rat oxidized cytochrome c variant predicts that the reduced rat variant will be even more stable than the already stabilized oxidized variant.     

Serotonergic Psychedelics Temporarily Modify Information Transfer in Humans

Background:

Psychedelics induce intense modifications in the sensorium, the sense of “self,” and the experience of reality. Despite advances in our understanding of the molecular and cellular level mechanisms of these drugs, knowledge of their actions on global brain dynamics is still incomplete. Recent imaging studies have found changes in functional coupling between frontal and parietal brain structures, suggesting a modification in information flow between brain regions during acute effects.

Methods:

Here we assessed the psychedelic-induced changes in directionality of information flow during the acute effects of a psychedelic in humans. We measured modifications in connectivity of brain oscillations using transfer entropy, a nonlinear measure of directed functional connectivity based on information theory. Ten healthy male volunteers with prior experience with psychedelics participated in 2 experimental sessions. They received a placebo or a dose of ayahuasca, a psychedelic preparation containing the serotonergic 5-HT_2A agonist N,N-dimethyltryptamine.

Results:

The analysis showed significant changes in the coupling of brain oscillations between anterior and posterior recording sites. Transfer entropy analysis showed that frontal sources decreased their influence over central, parietal, and occipital sites. Conversely, sources in posterior locations increased their influence over signals measured at anterior locations. Exploratory correlations found that anterior-to-posterior transfer entropy decreases were correlated with the intensity of subjective effects, while the imbalance between anterior-to-posterior and posterior-to-anterior transfer entropy correlated with the degree of incapacitation experienced.

Conclusions:

These results suggest that psychedelics induce a temporary disruption of neural hierarchies by reducing top-down control and increasing bottom-up information transfer in the human brain.     

脑电非线性分析监测在异丙酚靶控输注中的应用

目的:本研究采用脑电非线性分析监测技术,研究异丙酚靶控麻醉对不同脑区的作用,并探讨其临床意义。方法:选择40例择期行腹部手术的患者,随机分为异丙酚3μg/mL靶控输注组(A组)、异丙酚4μg/mL靶控输注组(B组),每组20例。麻醉方法采用全凭静脉异丙酚靶控麻醉,监测患者清醒时、诱导、术中、苏醒、出室时的脑电非线性参数—近似熵(ApEn)、关联维数(D2)和复杂度(Cx),以及血压(BP)、心率(HR)、脉搏血氧饱和度(SpO2)变化。结果:异丙酚镇静下患者各个脑区的非线性参数值均下降,差异有统计学意义(P<0.05);组内患者,术中与清醒时、苏醒相比较,ApEn、D2和Cx下降差异有统计学意义(P<0.05);A组与B组之间,同一阶段ApEn、D2、Cx下降幅度差异无统计学意义(P>0.05);异丙酚达到靶控浓度过程中脑区从额叶和顶叶区向颞叶和枕叶逐渐被抑制,停药以后脑区又从颞叶和枕叶区向额叶和顶叶逐渐恢复兴奋。结论:在麻醉的不同阶段、不同脑区监测到的脑电非线性参数不同;异丙酚3μg/mL靶控输注与异丙酚4μg/mL靶控输注,两组浓度对脑区的抑制在非线性监测下差异无统计学意义。     

结构优化的焓与熵

多参数的先导物优化可归纳为两部分：从微观结构上提高化合物的活性强度和选择性,从宏观性质上优化其物化性质、吸收和药代以及安全性质等,这些集中反映于药理活性和成药性中。内涵于化学结构中的这两部分是相互关联的,例如对靶标的高活性和高选择性的药物可容许物化、代谢和安全性质有更宽泛的表现。药物对靶标的亲和力（如平衡状态下的离解常数Ki）与体外活性（如EC50或IC50）是密切相关的,因而在初期优化中成为衡量化合物质量的主要指标。配体与靶标的亲和力或离解常数可转换为结合自由能,进而可用热力学实验方法将结合能＂化解＂成焓和熵的贡献,这样,在结构优化过程中,测定化合物自由能、焓和熵变,可从原子和基团的性质、取向、位置和距离的变化等更加微观的层面上,理解对活性的影响和量变的规律。配体的这些热力学特征与配体-蛋白复合物的结构生物学特征相结合,可深入揭示配体-受体的结合本质和呈现活性的内涵,从焓-熵的量变中把握结构变换对活性的影响,这是解析药物的作用机制和指导分子设计的有用方法,本文将以实例讨论热力学在结构优化中的应用。     

Thermodynamic analysis of antagonist and agonist interactions with dopamine receptors

The binding of [3H]spiperone to dopamine D-2 receptors and its inhibition by antagonists and agonists were examined in microsomes derived from the sheep caudate nucleus, at temperatures between 37 and 1 degree C, and the thermodynamic parameters of the binding were evaluated. The affinity of the receptor for the antagonists, spiperone and (+)-butaclamol, decreased as the incubation temperature decreased; the affinity for haloperidol did not further decrease at temperatures below 15 degrees C. The binding of the antagonists was associated with very large increases in entropy, as expected for hydrophobic interactions. The enthalpy and entropy changes associated with haloperidol binding were dependent on temperature, in contrast to those associated with spiperone and (+)-butaclamol. The magnitude of the entropy increase associated with the specific binding of the antagonists did not correlate with the degree of lipophilicity of these drugs. The data suggest that, in addition to hydrophobic forces, other forces are also involved in the antagonist-dopamine receptor interactions, and that a conformational change of the receptor could occur when the antagonist binds. Agonist binding data are consistent with a two-state model of the receptor, a high-affinity state (RH) and a low-affinity state (RL). The affinity of dopamine binding to the RH decreased with decreasing temperatures below 20 degrees C, whereas the affinity for the RL increased at low temperatures. In contrast, the affinity of apomorphine for both states of receptor decreased as the temperature decreased from 30 to 8 degrees C. A clear distinction between the energetics of high-affinity and low-affinity agonist binding was observed. The formation of the high-affinity complex was associated with larger increases in enthalpy and entropy than the interaction with the low-affinity state was. The results suggest that the interaction of the receptor with the G-proteins, induced or stabilized by the binding of agonist, leads to an increase in entropy and to negative heat capacity changes in the system.     

Some binding-related drug properties are dependent on thermodynamic signature

The binding affinity is determined by the Gibbs energy of binding (ΔG) which is the sum of enthalpic (ΔH) and entropic (?TΔS) contributions. Because the enthalpy and entropy contribute in an additive way to the binding energy, the same binding affinity can be achieved by many different combinations of enthalpic and entropic contributions; however, do compounds with similar binding affinities but different thermodynamic signatures (i.e., different ΔH, ?TΔS combinations) exhibit the same functional effects? Are there characteristics of compounds that can be modulated by modifying their thermodynamic signatures? In this paper, we consider the minimization of unwanted conformational effects arising during the development of CD4/gp120 inhibitors, a new class of HIV‐1 cell entry inhibitors. Competitive inhibitors of protein/protein interactions run the risk of triggering the very same signals that they are supposed to inhibit. Here, we show that for CD4/gp120 inhibitors, the magnitude of those unwanted effects is related to the proportion in which the enthalpy and entropy changes contribute to the binding affinity. The thermodynamic optimization plot (TOP) previously proposed to optimize binding affinity can also be used to obtain appropriate enthalpy/entropy combinations for drug candidates.     

Limitations of the maximum entropy principle in devising drug input rate

A computer program applying the principle of maximum entropy to the analysis of drug absorption rate has been developed. Plasma concentrations of amoxicillin obtained after oral and intravenous dosing have been analysed, together with simulated data corresponding to a complex input.Amoxicillin absorption rates devised by the program were similar to those obtained by a standard deconvolution method, although they were displayed as an almost continuous profile. However, improbable fluctuations were obtained with some data sets and the fraction absorbed was underestimated by 13%. With the simulated data, the maximum entropy program did not provide a better solution than the standard deconvolution procedure, and it was sensitive to the addition of random error and to the number of samples.The maximum entropy principle, as implemented in our computer program, may not have a better performance than standard deconvolution procedures, especially in human experiments where the number of blood samples is usually limited.