INTRA- AND INTERINDIVIDUAL VARIATION IN THE PHARMACOKINETICS OF TACROLIMUS (FK506) IN KIDNEY TRANSPLANT RECIPIENTS—IMPORTANCE OF TROUGH LEVEL AS A PRACTICAL INDICATOR

Background: Tacrolimus (FK506) is currently used as the primary immunosuppressant in clinical kidney transplantation in some centers. The purpose of this study was to evaluate the pharmacokinetics of this drug and to see if trough level, which has been used widely in therapeutic drug monitoring, can be used as an appropriate substitute for other pharmacokinetic measurement tests. Methods: The blood concentration-time curve was studied in 10 kidney transplant recipients on 26 Occasions after oral dosage of 2 to 18 mg every 12 hours. Whole blood concentration was measured by two-step irnmunoabsorption assay. Methylprednisolone was used as a concomitant immuno-suppressive drug. Results: The blood concentration-time curves showed remarkable interindividual variation. lntraindividual variation was also found, but the degree of variation was slight compared with interindividual variation. On 17 occasions of measurement in one patient, the dose was significantly correlated with trough (r = 0.684). C_max (r = 0.838) and AUC_0–12 (r = 0.817). In nine patients on nine occasions, however, the dose was not significantly correlated with trough (r = 0.351), C_max (r = 0.270) or AUC_0–12 (r = 0.355). t_max ranged from one to four hours (mean + SD; 2.8 + 1.3) and fluctuated in both intra- and interindividual measurements. In spite of a wide variation in the blood concentration-time-curve patterns, a highly significant linear relationship between trough and C_max or AUC_0–12 was observed in both intraindividual (C_max, r = 0.876; AUC_0–12, r = 0.926) and interindividual (C_max, f = 0.943; AUC_0–12, r = 984) measurements. Concluslons: We conclude that trough level is a practical acceptable indicator of the blood levels of tacrolimus, and can be used to monitor blood concentration.     

Lymphocyte β-adrenergic receptor binding in panic disorder

Lymphocyte beta adrenergic receptor binding using [¹²⁵I]CNP was determined in patients with panic disorder (N=4) or agoraphobia with panic attacks (N=17) and age- and sex-matched healthy subjects (N=22). The patients showed a significantly lower number of -adrenergic receptor binding sites and a significantly higher affinity of binding than healthy subjects. A past or present history of major depression in the patients did not alter these findings. These results are consistent with a growing body of knowledge implicating noradrenergic dysfunction in the pathophysiology of panic anxiety.     

快速康复外科理念在膀胱癌患者根治性全膀胱切除术围术期护理中的应用效果

目的 分析快速康复外科(FTS)理念在膀胱癌(BC)患者根治性全膀胱切除术围术期护理中的应用效果。方法 回顾性收集我院147例BC患者,均接受根治性全膀胱切除术治疗,将2017年1月～2018年10月在围术期接受常规护理干预的73例作为对照组,将2020年1月～2021年10月在围术期接受FTS理念干预的74例作为观察组,比较两组围术期情况、不同时间点(术前1d、术后1h、1d)疼痛程度、并发症。结果 观察组术后首次下床活动、术后首次排气以及住院时间均短于对照组(P＜0.05);两组不同时间、组间、交互作用下视觉模拟疼痛评分(VAS评分)比较,差异具有统计学意义(P＜0.05),两组术前1d VAS评分比较,无明显差异(P＞0.05);而与对照组术后1h、1d VAS评分相比,观察组均较低(P＜0.05);观察组、对照组并发症发生率分别为31.08%、41.10%,组间比较,无明显差异(P＞0.05)。结论 FTS理念应用于BC患者,能减轻疼痛程度,缩短术后首次下床活动、术后首次排气时间,促进术后恢复。     

羧酸酯酶1和羧酸酯酶2基因表达量与体质量指数的关系及其基因多态性分析

目的 通过检测健康志愿者的羧酸酯酶1 (carboxylesterase 1,CES1)和羧酸酯酶2 (carboxylesterase 2,CES2)的基因多态性和基因表达水平,探索CES1和CES2在代谢中的作用。方法 从48例健康志愿者获得血样并提取DNA,对DNA进行二代基因测序,并提取总RNA检测基因表达量。使用多元线性回归分析CES1和CES2基因表达量与性别、年龄、体质量指数(body mass index, BMI)的关系。结果 CES1的基因表达量为141.8(72.7,237.8),CES2的基因表达量为74.4(30.8,133.6)。多元线性回归分析中,BMI与CES2的基因表达有关,性别、年龄和BMI与CES1的基因表达无关。发现CES1 20个基因变异,其中10个会引起氨基酸序列改变;发现CES2 6个基因变异,其中2个引起氨基酸序列改变。结论 发现CES2的表达水平与BMI相关,CES1的表达水平与BMI无明显相关,基因预测结果提示CES1的遗传变异可能影响其功能表达。     

新疆维吾尔自治区精神障碍流行病学调查及影响因素研究

背景经济社会的发展、生活方式的转变及新型冠状病毒感染疫情的发生都对人群心身健康水平产生影响,进而可能使精神障碍的患病情况发生变化。然而,目前新疆维吾尔自治区的精神障碍流行病学调查资料尚不完善。目的 调查新疆维吾尔自治区北部（简称北疆）≥15岁人群的常见精神障碍患病率及影响因素,并同新疆维吾尔自治区南部（简称南疆）相关资料进行汇总与对比,得出全疆常见精神障碍患病情况,为制定相应的精神卫生规划提供科学依据。方法 于2021年11月至2022年7月,采用多阶段分层随机抽样法在北疆选取居民3 853例为研究对象。以社会人口学调查表、自评量表（12项一般用健康问卷、心境障碍问卷、90项症状清单等）及他评量表（汉密尔顿抑郁量表、贝克-拉范森躁狂量表、简明精神病量表等）作为调查工具,以国际疾病分类第10版（ICD-10）中的精神与行为障碍分类为诊断标准,由两名具有≥5年工作经验的精神科医师对纳入居民进行精神障碍诊断,诊断不一致者由精神科主任或副主任医师进行二次诊断。结果 北疆地区常见精神障碍时点患病率为9.71%(374/3 853),年龄调整率为10.07%;全疆常见精神障碍时点患病率为9.69%...     

Neuroendocrine aspects of the serotonergic hypothesis of depression

This review examines the role of serotonin (5-HT) in depression. Dysfunction of serotonergic neurons has been implicated as one of the causes of endogenous depression. Since serotonergic neurons innervate the hypothalamus and these neurons send collaterals to several other brain areas, it is possible that hypothalamic sites which control hormone secretion receive the same serotonergic afferents that innervate other limbic areas in the brain. Several investigators have devised neuroendocrine challenge tests measuring the effect of 5-HT agonists on plasma cortisol and prolactin in depressed patients. These tests help to identify dysfunctional 5-HT neurons, and are a "window into the brain." The secretion of cortisol and prolactin is increased predominantly by 5-HT1 receptors. However, changes in 5-HT2 receptors have also been implicated in depression. Results from our laboratory and by others suggest that brain serotonergic neurons stimulate renin and vasopressin secretion by activation of 5-HT2 receptors. Therefore, the renin and vasopressin response to 5-HT agonists should be included in neuroendocrine tests of serotonergic function in affective disorders. Since antidepressants produce a decrease in the density of 5-HT2 receptors, renin and vasopressin could be used to evaluate the antidepressant potential of new drugs.     

Anti-conflict efficacy of buspirone following acute versus chronic treatment

In many animal studies, acute treatment with the novel anxiolytic agent buspirone exhibits only minimal anxiolytic efficacy (i.e., increases in punished responding) when compared to benzodiazepines and barbiturates. The present studies examined the effects of acute pre-test challenges with buspirone in subjects receiving chronic post-test buspirone or saline treatments. Chronic post-test treatment with buspirone (4 mg/kg/day for 4 weeks, followed by 8 mg/kg/day for 12 weeks) did not significantly affect CSD behavior. Consistent with previous reports, acute pre-test administration of buspirone (0.125–2 mg/kg, IP) to subjects receiving chronic post-test saline treatment resulted in only a modest anti-conflict effect in the CSD paradigm (approximately ten shocks over control). In contrast, subjects chronically treated with buspirone exhibited a dramatically greater anti-conflict effect following acute challenge with buspirone (up to 40 shocks over control). These data are consistent with the hypothesis that the full anxiolytic efficacy of buspirone requires repeated administration.     

An evaluation of the elevated plus-maze test using the novel anxiolytic buspirone

Previous work suggests that the elevated plusmaze test of anxiety is insensitive to the anxiolytic effects of the novel anxiolytic buspirone, which shows an anxiogenic-like profile in this test. This paper examines some of the possible reasons for this and the role that buspirone's agonist activity at 5-HT_1A receptors plays in this effect. A variety of 5-HT_1A receptor agonists (p-aminophenylethylm-trifluromethylphenyl piperazine, (+)- and (-)-MDL 72832) showed similar activity to buspirone, as did the related compound ipsapirone. (-)-MDL 72832 was more potent than (+)-MDL 72832, in keeping with its stereoselective action at 5-HT_1A receptors. The ₂-adrenoceptor antagonist properties of 1-pyrimidinyl piperazine, a metabolite of buspirone, did not appear to be relevant to this action of buspirone as neither it nor idazoxan showed an anxiogenic-like profile. Neither chronic treatment with buspirone (1 mg/kg SC twice a day for 16 days) nor depletion of 5-HT withp-chlorophenylalanine changed the anxiogenic-like activity of buspirone in the elevated plus-maze test. These results suggest that an agonist action at postsynaptic 5-HT_1A receptors mediates the anxiogenic-like effects of buspirone in the elevated plus-maze test and that this test may either be insensitive to certain classes of anxiolytics or is measuring something unrelated to human anxiety states.     

神经症的性压抑与心理因素的相关性研究

研究神经症患者潜在人格与性压抑和情绪的相关性.方法:对124例神经症患者进行了婚姻质量问卷(性生活、婚姻质量部份)、抑郁自评量表(以下简称SDS)、焦虑自评量表(以下简称SAS)及自编的性生活调查问卷、主题统觉测验(以下简称TAT)测评.结果:1、神经症伴性障碍组TAT潜在人格与对照组相比,在支配、性、援助、躯体社会攻击、财产破坏欲求、自我攻击、情绪变化欲求和情绪言语攻击性、躯体社会攻击、引诱、缺乏、丧失、灾害、丧失支持、躯体伤害压力上均较对照组显著增高,而成就欲求下降(P<005-001);与神经症无性障碍组相比,神经症伴性障碍组的成就、支配、教养、性欲求得分显著增高,情绪言语攻击欲求得分下降(P<001～005);2、神经症伴性障碍组的性生活质量低,性频度、性后快感均低.3、SDS、SAS与TAT中的负性欲求呈明显的相关性,性行为调查与婚姻质量量表中的性行为呈正相关.结论:神经症的性压抑与其潜在人格有密切的相关性.     

父母文化程度与高师学生心理健康问题研究

目的 了解高师学生心理健康现状和父母文化程度对高师学生心理健康水平的影响。方法 对河南省部分高师学生进行问卷调查。结果 河南省大部分高师学生心理健康状况是好的和比较好的；15.13%的高师学生心理健康状况不良，教师、咨询人员和家长应高度重视，密切配合，正确地对他们进行引导和教育。结论 父母文化程度不同对高师学生心理健康水平的影响有差异。但差异不显著。