Carbamazepine-Valnoctamide Interaction in Epileptic Patients: In Vitro/In Vivo Correlation

Six patients stabilized with carbamazepine (CBZ) therapy received an 8-day “add-on” supplement of valnoctamide (VCD), a tranquilizer available over the counter (OTC) in several European countries that exhibits promising anticonvulsant activity in animal models. During VCD intake, serum levels of the active CBZ metabolite, carbamazepine-10,ll-epoxide (CBZ-E), increased fivefold from 1.5 ± 0.7 μg/ml at baseline to 7.4 ± 4.4 μg/ml after 4 days of VCD therapy and 7.7 ± 3.1 ^g/ml after 7 days of VCD therapy (means ± SD, p < 0.01). In 4 patients, the increase in serum CBZ-E levels was associated with clinical signs of CBZ intoxication. CBZ-E levels returned to baseline after VCD therapy was discontinued. Serum CBZ levels remained stable throughout the study. The interaction observed in this study is similar to that described in patients treated with CBZ and valpromide (VPD, an isomer of VCD). In a mechanistic study, therapeutic concentrations of VCD inhibited hydrolysis of styrene oxide in human liver mi-crosome preparations. Thus, VCD is a potent inhibitor of microsomal epoxide hydrolase (IC₅₀ 15 μM). There was a striking similarity between in vitro and in vivo inhibition potencies. In this study, VCD clearance was higher in epileptic patients (treated with CBZ) than in healthy subjects.     

Concepts of Hemopoietic Cell Amplification. Synergy, Redundancy and Pleiotropy of Cytokines Affecting the Regulation of Erythropoiesis

Hemopoietic cell amplification in vivo is regulated by various mechanisms which appear to be under control of many hemopoietic growth factors. Quiescent stem cells can be activated into cell cycle, dividing progenitor cells can reduce their cell cycle time, the differentiation velocity (i.e. transit-time) can be manipulated, apoptosis can be prevented, and finally, at least in the murine system, migration of cells between the microenvironments in marrow and spleen may take place. Perturbations of any of the parameters by which these mechanisms are defined, will affect in vivo blood cell production. In this review the consequences of these perturbations, and the role of growth factors herein, are discussed. These fundamental aspects of the regulation of hemopoiesis are illustrated with recent data showing the synergistic, redundant and pleiotropic effects of SCF, IL-11, EPO and G-CSF on the in vivo formation of erythrocytes. Given the overwhelming number of growth factor-related studies that are now appearing, a re-evaluation of data, available in the literature, in the context of the mechanistic approach of growth factor-dependent hemopoiesis which is presented in this paper, seems to be useful and warranted.     

造血因子治疗中子急性放射病的实验研究

目的通过观察造血生长因子-重组人白细胞介素-11(rhIL-11)和重组人粒细胞集落刺激因子(rhG-CSF)联合应用的方法对中子急性放射病狗的治疗效果,探讨中子损伤治疗的救治方法。方法14只雄性成年比格狗随机分为照射对照和rhIL-11+rhG-CSF治疗组。所有动物均接受90%裂变中子照射,治疗组于照后当天开始每天1次皮下注射rhG-CSF10μg·kg-1·d-1和rhIL-1150μg·kg-1·d-1,给药时间分别为14和21d。照射后观察动物的外周血象、外周血CD4+/CD8+比值变化、骨髓CFU-E及组织病理学改变。结果照射后早期对照组动物全部发生不同程度的呕吐,治疗组仅1只动物呕吐。照射后30d照射对照组死亡3只,治疗组动物全部存活。照后治疗组外周血白细胞数和恢复期血小板数明显高于照射对照组。照射后1、21和33d治疗组外周血CD4+/CD8+比值分别为照射对照组1·24、1·55和2·15倍。照射后1和33d治疗组动物骨髓CFU-E分别为照射对照组的5·25和2·34倍(P<0·01)。结论rhIL-11+rhG-CSF联合给药可明显促进中子照射所致骨髓型急性放射病狗的造血和免疫功能恢复,为细胞因子应用于中子急性放射病的临床治疗提供了实验依据。     

重组人白介素11对豚鼠血小板减少的治疗作用

应用抗血小板血清造成豚鼠血小板减少症动物模型 ,观察人重组白细胞介素 11(rHuIL 11)对豚鼠血小板减少症的治疗作用 ,结果显示rHuIL 112 0 0 ,10 0 ,5 0 μg·kg-1均可明显升高豚鼠的血小板计数 ,增加骨髓巨核细胞集落生成单位 (CFU Meg)细胞集落数 ,与生理盐水对照组比较有明显差异。说明rHuIL 11对豚鼠血小板减少症有明显的治疗作用     

白细胞介素－11基因治疗促进放射损伤小鼠造血恢复的实验研究

白细胞介素－１１（Ｉｎｔｅｒｌｅｕｋｉｎ－１１，ＩＬ－１１）是一种新的造血生长因子，体内、外实验结果显示ＩＬ－１１具有显著的造血促进作用，它能作用于早期的造血干细胞及祖细胞，促进其增殖和分化。为了探讨ＩＬ－１１基因治疗放射损伤后造血恢复的促进作用，我们构建了含人ＩＬ－１１ｃＤＮＡ的逆转录病毒载体，并转染小鼠成纤维细胞系ＮＩＨ－３Ｔ３，经筛选获得３株高表达ＩＬ－１１的转染细胞亚克隆，用高表达ＩＬ－１１的转染细胞作为载体细胞，进行了ＩＬ－１１基因治疗对放射损伤小鼠造血系统影响的实验研究。结果表明ＩＬ－１１基因治疗能明显缩短亚致死量放射损伤小鼠白细胞降低的时间，促进外周血白细胞、血小板和红细胞压积的恢复。提示ＩＬ－１１基因治疗对放射损伤造成的造血功能低下具有潜在的应用价值。     

Unusual segregation of t(11;22) resulting from crossing-over followed by 3:1 disjunction at meiosis I

Reciprocal translocation t(11;22)(q23;q11) is of particular interest because the unbalanced offspring of the translocation carriers usually present with a supernumerary derivative chromosome 22. This common unbalanced karyotype is the result of 3:1 chromosome segregation during meiosis. We report the third case of a rare segregation pattern of a paternal 11; 22 translocation. The proband's karyotype revealed the presence of a der(11) and two copies of a der(22), i.e. 47, XX, t(11; 22)(q23;q11), +der(22) t(11;22)pat. The karyotype is the result of paternal 3:1 segregation after crossing-over involving the derived and the normal chromosome 22, as revealed by chromosome polymorphism analysis. Contrary to the preferential maternal transmission of this common unbalanced translocation, the data from the literature, including our case, may suggest preferential paternal transmission of this rare type of unbalanced translocation.     

Effect of brucine on mouse nonspecific immune responses

目的：观察镇痛有效剂量的布鲁生（Ｂｒｕ）对正常小鼠及Ｃｙｃ所致免疫低下小鼠非特异免疫功能的影响．方法：测定小鼠碳粒廓清能力、免疫器官重量及外周血ＷＢＣ，小鼠ＰＭ吞饮中性红及产生ＩＬ１能力．结果：Ｂｒｕ对正常鼠碳粒廓清能力、免疫器官重量、外周血ＷＢＣ、ＰＭ吞噬功能及产生ＩＬ１能力仅有轻微促进作用（Ｐ＞００５），而对被Ｃｙｃ降低的上述非特异免疫反应，Ｂｒｕ呈剂量依赖性的增强作用（Ｐ＜００５或Ｐ＜００１），作用以１０ｍｇ·ｋｇ－１时最好．结论：Ｂｒｕ在镇痛有效剂量ｉｐ时，对小鼠非特异免疫功能有剂量依赖性及功能依赖性的调节作用．     

CD11/CD18在烧伤早期中性粒细胞对内皮细胞粘附中的作用及变化

为了解烧伤早期病人中性粒细胞(PMN)膜表面 CD11a/CD18和 CD11b/CD18变化规律及其在烧伤早期 PMN 对内皮细胞(EC)粘附及损伤中的作用,为临床抗白细胞粘附治疗提供依据。将烧伤早期 PMN 与体外培养的人脐静脉内皮细胞(HUVEC)孵育24小时后,观察烧伤早期 PMN 与 EC 粘附百分率和烧伤早期 PMN 引起内皮细胞单层流出液生成速度(Jv)和滤过系数(kf)变化,CD11/CD18单抗(mAb)对烧伤早期 PMN-EC 粘附和内皮单层 kf、Jv 值影响。并应用流式细胞术检测烧伤病人伤后1周内 PMN 膜表面 CD11a/CD18和 CD11b/CD18的数量变化。结果显示严重烧伤病人伤后第1天 PMN细胞膜表面 CD11a/CD18和 CD11b/CD18明显升高达峰值,并在1周内仍维持于高水平。烧伤早期PMN 与 EC 粘附增加并可致内皮单层 kf、Jv 值明显升高,CD11a/CD18mAb 和 CD11b/CD18mAb 可降低粘附百分率70%～80%,并降低烧伤早期 PMN 诱导增高的内皮单层 kf、Jv 值(P<0.01)。提示烧伤后 PMN 迅速表达 CD11a/CD18和 CD11b/CD18,加强与 EC 间粘附,并可使内皮单层通透性增高,CD11a/CD18mAb 和 CD11b/CD18mAb 降低烧伤早期 PMN 与 EC 粘附,减轻烧伤早期 PMN 所导致的内皮单层通透性增高,从而保护内皮细胞。