鸡甲胺磷中毒性神经肌病电生理测定及地塞米松干预研究

目的了解甲胺磷中毒迟发性神经病的电生理变化特点，探讨地塞米松对有机磷中毒迟发性神经病（OPIDN）的保护作用。方法莱亨母鸡随机分为3组，A组：不染毒；B组：染毒，盐水；C组：染毒，地塞米松治疗。甲胺磷经消化道染毒，从染毒后第2天开始B、C组分别每天给盐水和地塞米松1周（2ml／kg），染毒后1、2、3、4、周取鸡坐骨神经进行电生理检测。结果甲胺磷致迟发性神经病早期以轴索损害,为主（波幅降低），8继之出现脱髓鞘改变（运动神经传导速度减慢），但各组间比较差异无显著性，P〉0．05。结论（1）利用甲胺磷染毒莱亨鸡可成功构建迟发性神经病模型。（2）电生理检测阳性率高，且早于临床体征的出现，是诊断迟发性神经病的客观指标之一。（3）地塞米松不能防止OPIDN的发生。     

地塞米松与庆大霉素交替湿敷治疗诺维苯化疗性静脉炎的疗效观察

目的：探讨地塞米松与庆大霉素交替湿敷治疗诺维苯化疗性静脉炎的临床疗效。方法：对20例由诺维苯所致化疗性静脉炎的患者，根据其不同的血管毒性反应采用地塞米松与庆大霉素交替湿敷。结果：20例患者中，治愈率为100％。其中4～7d内痊愈14例，占总治愈率的70％，7～12d内痊愈的有5例，占总治愈率的25％，15d内痊愈的有1例(5％)，占总治愈率的5％。结论：地塞米松及庆大霉素交替湿敷可有效地治疗诺维苯化疗性静脉炎，并有积极的预防作用，本方法简便易行，价格低廉，疗效较好，值得临床推广应用。     

窒息新生儿肾上腺皮质激素水平的变化及临床意义分析

[目的] 了解窒息新生儿激素水平在应激状态下的改变，探讨地塞米松对窒息新生儿体内激素水平的影响。[方法] 分别对38例足月窒息儿(A组、B组)、20例足月健康儿(C组)，于生后第1、2、3、5、10d抽血检测血浆儿茶酚胺(CA)、皮质醇(Cor)、醛固酮(A1d)，观察其水平变化。[结果] ①C组血浆Cor、A1d随日龄增长而下降，CA水平较稳定；②A组生后第1d三个指标均明显高于C组(P＜0．01)，第10d与C组比较差异无显著意义(P＞0．05)；②B组地塞米松治疗后3-5d，上述三指标均有不同程度下降，但仅血浆CA较A组相应日龄值明显降低(P＜0．01)，而血浆Cor、A1d值下降无统计学意义(P＞0．05)，第10d恢复至正常组水平。[结论] 新生儿生后CA、Cor、Ald的正常值应依日龄而定；窒息应激时，易发生内分泌失衡。而短期Dex应用对内分泌系统仅产生短暂轻度抑制。     

The dexamethasone suppression test in dementia

The dexamethasone suppression test (DST) was performed on 13 patients with multi-infarct dementia (MID), 5 patients with primary degenerative dementia (PDD) and 18 elderly controls. Abnormal lack of suppression was found in 7 demented patients (3 with PDD, 1 mild and 2 severe, and 4 with MID, 1 mild and 3 severe), and in 2 of the controls. Only one demented patient was depressed. The value of DST in the differential diagnosis of dementia from the major depressive disorders is discussed.

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Sommario Il test di soppressione al desametazone (DST) è stato applicato a 13 pazienti con demenza multi-infartuale (MID), a 5 pazienti affetti da demenza degenerativa primaria (PDD), e a 18 controlli (anziani). Una nonsoppressione è stata ritrovata in 7 pazienti affetti da demenza (3 di tipo PDD, in 1 caso di grado moderato ed in 2 casi severo, e 4 di tipo MID, in 1 caso moderato ed in 3 casi severo). Solo uno dei pazienti affetti da demenza si presentava contemporaneamente affetto da depressione. Viene discussa l’utilità del DST nel giudizio diagnostico-differenziale tra la demenza ed il disturbo depressivo maggiore.

     

地塞米松对大鼠睾丸间质细胞睾酮分泌的影响及机理研究

目的 观察地塞米松(dexamethasone，DEX)以及DEX和RU486共同作用时对hCG诱导的大鼠间质细胞睾酮分泌的影响和间质细胞中原癌基因c-myb表达的情况，从而探讨DEX的作用机制。方法 用放射免疫方法测定离体大鼠间质细胞的睾酮分泌量；用S-P免疫组织化学方法观察离体大鼠间质细胞中c-Myb蛋白表达的变化。结果 10^-8mol／L的DEX可降低hCG诱导的离体大鼠间质细胞睾酮分泌．并使间质细胞c-Myb蛋白免疫组织化学染色明显下降。上述DEX作用可被糖皮质激素受体功能阻断剂RU486(10μmol／L)所阻断。结论 DEX很可能通过降低间质细胞中c-Myb蛋白表达而抑制hCG诱导的间质细胞睾酮分泌。     

In vivo pharmacokinetic study for the assessment of poly(L-aspartic acid) as a drug carrier for colon-specific drug delivery

Glucocorticoids remain one of the mainstays of therapy for acute attacks of inflammatory bowel disease despite systemic side effects that limit their use. Prodrugs that selectively deliver glucocorticoids to the colon may lower the required dose and side effects. Because enzymes of gut microflora are able to cleave certain peptide and ester bonds, the ability of an ester prodrug consisting of dexamethasone (DX) as model drug and poly(L-aspartic acid) (weight-average mol wt=30,000) as drug carrier was investigated to selectively release the drug in the large intestine. Prodrug and drug solutions (1.18 mg DX/ml DMSO) were administered to two groups of male Sprague-Dawley rats by intragastric infusion using an ALZET^® osmotic pump. All rats were infused for sufficient time to achieve steady state in both blood and GI-tract tissues. DX concentrations in blood and tissue samples were measured with HPLC. The steady state DX concentrations at these sites were used to calculate a drug delivery index (DDI). DX blood concentrations were significantly lower (p<0.05) after intragastric administration of the prodrug. Moreover, prodrug administration resulted in significantly higher DX concentrations in the cecum and colon mucosa and the cecum muscle tissue compared to DX administration (p<0.05). The prodrug led to an increase of the DX concentration in the large intestinal tissues by factors of 1.3–2.0 and to an 1.3-fold decrease of DX blood concentrations. Thus, this novel conjugate should both increase efficacy and reduce toxicity to some extent.     

地塞米松治疗急性脑血管病对下丘脑─垂体─肾上腺皮质轴功能改变的效应观察

对68例基底节区急性脑血管病者应用地塞米松观察治疗，结合地塞米松抑制试验，探讨其对H／P／A功能改变的相关效应。结果显示应用地塞米松后血清ACTH、皮质醇水平均减低，以脑梗塞着为明显。提示外源性皮质激素反馈性抑制H／P／A分泌机能，其程度与脑血管病病情有关。     

Glucocorticoid receptor properties and glucocorticoid regulation of glutamine synthetase activity in sensitive C6 and resistant C6H glial cells

The relationship between induction of glutamine synthetase activity by dexamethasone and binding of the steroid to cytosolic glucocorticoid receptors was examined in sensitive C6 and resistant C6H glial cell cultures. Glutamine synthetase activity increased 3-4-fold when C6 cultures were exposed to 7.6 x 10(-6) M dexamethasone. This inductive response was reversible, dose-dependent (ED50 approximately 2 x 10(-8) M), required de novo protein and RNA synthesis, and was elicited only by glucocorticoid steroids. Progesterone, but not epicortisol, antagonized the dexamethasone-induced enzyme increase. In contrast, only a slight inductive effect was observed in dexamethasone-treated C6H cells. Competitive binding assays demonstrated that specific binding of [3H]-dexamethasone to cytosolic receptors was also dose-dependent. The ED50 was approximately 10(-8) M for both C6 and C6H cells. Scatchard analysis revealed that each C6 cell contained approximately 10,800 receptor sites and that the equilibrium dissociation constant (Kd) was 4.5 x 10(-9) M. Each C6H cell possessed approximately 12,200 sites, and the Kd was 6.7 x 10(-9) M. Unlabeled dexamethasone and cortisol (but not epicortisol) competed effectively with [3H]-dexamethasone for binding to cytosolic receptor sites and nuclear sites of both cell types. These results suggest that induction of glutamine synthetase activity in dexamethasone-treated C6 cells is a glucocorticoid-directed response. Since C6H cells are refractory in this regard but contain functional cytosolic receptors which interact with cell nuclei, the basis for their resistance appears to involve some step beyond these cellular processes.     

Recovery of Fertility Following Vasovasotomy

Wiederherstellung der Fertilität nach Vasovasostomie
Bericht über einen 29jährigen Mann, der 3 Jahre nach einer Vasektomie refertilisiert wurde. Während die Spermatozoendichte 2 Jahre später 28–50 Mill./ml betrug, lag der Motilitätsgrad nur bei 1%. Die morphologische Qualität war normal. 5 Monate später wurde der erste Spermatozoenpenetrationstest durchgeführt, der keine Penetration der Hamster-Eier ergab. Die Motilität war zu diesem Zeitpunkt ohne jede Therapie auf 50% angestiegen; der Isojima-Agglutinationstest zeigte einen Titer von 1:128, der Postcoitaltest ergab Kopf-Kopf-Agglutinationen (4+). Eine Behandlung mit Dexamethason (1 mg 2 × täglich peroral für 1 Monat) ergab, daß die Ehefrau nach 2 Monaten schwanger wurde; zu dieser Zeit fand man im Penetrationstest 16% positive Befunde, keine Agglutination mehr.     

HPA axis dysregulation in mice overexpressing corticotropin releasing hormone.

BACKGROUND: Hypersecretion of corticotropin-releasing hormone (CRH) in the brain has been implicated in stress-related human pathologies. We developed a transgenic mouse line overexpressing CRH (CRH-OE) exclusively in neural tissues to assess the effect of long-term CRH overproduction on regulation of the hypothalamic-pituitary-adrenal (HPA) axis. METHODS: Male transgenic CRH-OE(2122) mice on a C57BL/6J background were used. Littermate wildtype mice served as control animals. Basal plasma corticotropin and corticosterone concentrations were measured, and adrenal gland weight was determined. A dexamethasone suppression test measured the effects of long-term CRH hypersecretion on negative feedback control. Additionally, we measured plasma corticosterone concentrations in reaction to stress. RESULTS: CRH-OE(2122) mice showed elevated basal plasma corticosterone concentrations, hypertrophy of the adrenal gland, and dexamethasone nonsuppression. Basal plasma ACTH concentrations of wildtype and CRH-OE(2122) mice did not differ significantly. In reaction to stress, CRH-OE(2122) mice showed a normal corticosterone response. CONCLUSIONS: The HPA axis abnormalities observed in CRH-OE(2122) mice suggest that long-term hypersecretion of CRH in the brain can be a main cause of HPA axis dysregulation. The alterations in HPA axis regulation are reminiscent of changes reported in major depressive disorder. As such, these CRH -OE(2122) mice may model the neuroendocrine changes observed in major depressive disorder.