Effects of manipulating catecholamines on the incidence of the preovulatory surge of of luteinizing hormone and ovulation in the rat: evidence for a necessary involvement of hypothalamic adrenaline in the normal or 'midnight' surge

The preovulatory surge of luteinizing hormone reaches a maximum at 18.00 h on the day of pro-oestrus in female rats maintained with regular lighting from 06.00 to 20.00 h. This surge is initiated by a discharge of luteinizing hormone-releasing hormone into hypophysial portal blood. In this study, drugs which affect catecholamine-mediated neurotransmission were administered on the day of pro-oestrus and the effects on serum concentrations of luteinizing hormone and on subsequent ovulation were observed. alpha-Methyl-p-tyrosine, diethyldithiocarbamate and SKF 64139 inhibit catecholamine synthesis at the level of tyrosine hydroxylase, dopamine beta-hydroxylase and phenylethanolamine N-methyltransferase, respectively. Although alpha-methyl-p-tyrosine suppressed ovulation, it had a negligible effect on the incidence of the preovulatory surge. In contrast, the various treatments with diethyldithiocarbamate and SKF 64139 resulted in a minimal occurrence of the 18.00 h surge; at relatively low doses, however, these drugs frequently elicited a surge at 22.00 or 24.00 h which invariably resulted in ovulation. The failure of the surge after diethyldithiocarbamate or SKF 64139 was not associated with a loss of pituitary sensitivity to luteinizing hormone-releasing hormone. In terms of the hypothalamic concentration of dopamine, noradrenaline, adrenaline and 5-hydroxytryptamine at 18.00 h on pro-oestrus, the only common effect of diethyldithiocarbamate and SKF 64139, given in a dose which blocks the surge, was a severe depletion of adrenaline; alpha-methyl-p-tyrosine failed to produce this effect despite inducing a marked depression of dopamine and a moderate loss of noradrenaline. Neither the increase in hypothalamic dopamine after diethyldithiocarbamate, nor the alpha 2 receptor blocking properties of SKF 64139 appear to be relevant in this context since injections of L-dopa or piperoxane, an alpha 2 receptor antagonist, were without effect on the surge or ovulation. The failure of the surge after prazosin, an alpha 1 receptor antagonist, indicates that the function of adrenaline may be mediated postsynaptically by alpha 1 receptors. Clonidine, an alpha 2 receptor agonist which reduces the turnover rate of hypothalamic adrenaline, had effects of the surge and ovulation which were comparable to those of diethyldithiocarbamate and SKF 64139, the relatively low doses causing some of the surges to occur at 24.00 instead of 18.00 h and higher doses suppressing the surge at both times and thus preventing ovulation.(ABSTRACT TRUNCATED AT 400 WORDS)     

改良Mini-CEX联合DOPS评价体系在麻醉科住院医师规培中的实践效果

目的探索以改良迷你临床演练评估(Mini-CEX)联合操作技能直接观察评估(DOPS)评价体系在麻醉科住院医师规培中的实践效果。方法以2017年与2018年进入某院麻醉科住院医师规范化培训基地的32名学员为研究对象,随机分为对照组和试验组各16名。对照组采用麻醉科传统规培模式,仅在年终考核时进行Mini-CEX、DOPS考核;试验组在传统规培模式基础上采用改良Mini-CEX联合DOPS评价模式,每月进行1次改良Mini-CEX、DOPS考核,包括年终考核共6次考核。对比2组学员年终考核成绩、首次考核成绩及教学满意度。结果试验组年终考核成绩的改良Mini-CEX评分、DOPS评分显著高于对照组,且试验组年终考核成绩明显优于首次考核成绩。试验组住院医师对教学满意度较对照组有明显提高。结论改良Mini-CEX联合DOPS评价体系有助于提高麻醉科住院医师规培的临床综合能力和操作技能水平,提升教学满意度和临床麻醉教学质量,值得推广与应用。     

Reduction of nerve growth factor receptor immunoreactivity in ischaemic gerbil hippocampal CA1 neurons after treatment with L-threo-3,4-dihydroxyphenylserine (DOPS)

Abstract

Nerve growth factor (NGF) synthesis in cultured mouse L-M fibroblast and astroglial cells can be increased after the treatment with L-threo-3,4-dihydroxyphenylserine (DOPS). Since the increase of NGF is not blocked by the treatment with decarboxylase inhibitor, DOPS may have direct effect to increase the NGF content. NGF and its receptor (NGFR) are suggested to play an important role in the neuronal survival and regeneration under pathologic conditions. In this study, we studied a possible protective effect of DOPS against the hippocampal CA1 cell death after transient forebrain ischaemia in gerbils in relation to the change of NGFR immunoreactivity. We found that treatment with DOPS (300 mg kg^–1) in combination with a decarboxylase inhibitor (benserazide, 10 mg kg^–1) protected ischaemic hippocampal CA1 cell against delayed neuronal death (neuronal density = 125 ± 24 mm^–1) as compared to the treatment with vehicle (49 ± 11 mm^–1) (p < 0.01). The immunoreactivity for NGFR was scarcely present in the sham-control CA1 area but was induced from 1 h and markedly expressed at 7 days after recirculation in the vehicle group. However; it was slightly and transiently induced from 8 h to 2 days in the DOPS plus benserazide treated group. These data suggest that the protective role of DOPS on the ischaemic hippocampal CA1 cells may act through the NGF and its receptor system. [Neurol Res 1994; 16: 201–204]     

Interaction of resveratrol with membrane glycerophospholipids in model system in vitro

Resveratrol is a polyphenol that among other sources occurs in grapes and for this reason, red wines also contain considerable amounts of this compound. Interactions of resveratrol with pure molecular species of phosphatidylcholine (PC), phosphatidylethanoloamine (PE) and phosphatidylserine (PS) were studied with the Langmuir technique on monolayers and with differential scanning calorimetry on unilamellar liposomes. Resveratrol caused a modest increase in the mean molecular area (MMA) of dipalmitoyl-PC (DPCC) and PE (DPPE) monolayers, but profoundly increased the MMA of dipalmitoyl-PS (DPPS). The resveratrol-induced increase in MMA was enlarged in PS species containing stearolyl and oleoyl acyls suggesting that increase in the acyl chain length and unsaturation enhanced the resveratrol–phospholipid interaction. In liposomes resveratrol lowered T_m (main transition temperature) and increased T_C1/2 (transition interval) in DPPE, DPPS and 1-palmitoyl-2-oleoyl-PS (POPS), suggesting that resveratrol causes an increase in the anisotropy of these liposomes. In DPPE and POPS liposomes resveratrol caused a lowering of ΔH, further substantiating a pure enhancement of anisotropy for these molecular species. However, resveratrol caused a marked increase of ΔH in DPPS liposomes, indicating that, in addition to increase anisotropy, DPPS and resveratrol attracted each other specifically. This study has clearly shown interactions between resveratrol and glycerophospholipids on a molecular level and that these interactions are influenced by the acyl chain length, degree of unsaturation and head group of the lipids.     

DDC-induced retrograde amnesias prevented by injections of dl-DOPS.

Injection of a dopamine beta-hydroxylate inhibitor, diethyldithiocarbamate (DDC) in rats 30 min prior to training of a step-down passive avoidance task impaired performance of the task 24 hr later. Similarly, injection of DDC 30 min prior to testing blocked retrieval of a passive avoidance habit trained in normal rats the previous day. Injection of a direct norepinephrine (NE) precursor, dl-thero 3,4-dihydroxyphenylserine (DOPS) 60 min before DDC prevented both amnesias. These data support the hypothesis that reduced levels of NE are responsible for DDC-induced amnesias.     

重组人内皮抑素DOPS胶束的制备及抑瘤效应研究

目的:本研究采用二油基磷脂酰丝氨酸(DOPS)制备包裁重组人内皮抑素的胶束,并考察其体内外抑瘤效应.方法:研究DOPS制备胶束的理化性质,考察重组人内皮抑素DOPS胶束对肿瘤细胞生长、鸡胚绒毛尿囊体内血管生长的影响及对H22肝癌荷瘤小鼠的肿瘤抑制效果.结果:制备的重组人内皮抑素DOPS胶束的粒径为(117.7±21.4)nm,Zeta电位为+18.1 mV,包封率为96.54%.该胶束明显抑制MCF-7肿瘤细胞的生长和增殖,抑制率为32.02%;对鸡胚绒毛尿囊血管新生也有明显的抑制作用,剂量越大,抑制作用越强.与单独使用重组人内皮抑素相比,该胶束抑制H22肝癌荷瘤小鼠肿瘤生长,抑制率达到55.42%.结论:以DOPS胶束作为药物载体可有效地增强重组人内皮抑素的抑瘤效应.     

DOPS在外科实习医师技能操作考核中的应用探讨

目的探讨临床操作技能直接观察评估考核(DOPS)在外科实习医师"换药"操作考核中的应用价值。方法以徐州医科大学2017届和2018届在我院实习的临床医学专业46名本科实习医师为研究对象,将其随机分为研究组和对照组。研究组在第1周末、第2周末、第3周末、第4周末进行DOPS评估操作考核;对照组在第1周末、第2周末、第3周末进行传统操作考核,第4周末进行DOPS操作考核。比较研究组和对照组第4周末DOPS考核的平均分数及教师、实习医师对考核的满意度。结果研究组第4周末DOPS考核平均分高于对照组(85.25±2.57)分vs.(76.64±4.96)分;研究组教师满意度为高于对照组教师满意度(7.42±0.41)分vs.(5.76±1.12)分;研究组实习医师满意度为高于对照组实习医师满意度为(7.43±0.85)分vs.(6.17±1.26)分;差异均有统计学意义(P<0.05)。结论DOPS评价系统应用于外科实习医师的操作考核中,可有效提高实习医师的操作水平,增加教师与实习医师的满意度。     

DOPS和Mini-CEX在临床技能考评中的联合应用研究

临床技能培养是临床医学专业教育的重要一环,具体带教中需要选择适宜的评估工具。现阶段多应用临床操作直接观察评估（direct observation of procedural skills,DOPS）和迷你临床演练评估（mini clinical evaluation exercise,Mini-CEX）,但单独运用其中之一进行评估具有一定缺陷。本研究基于国内外DOPS和Mini-CEX在临床技能考评中的应用情况,提出联合应用方案,拟将该方案用于本科临床教学和住院医师规范化培训中,以获得更为全面、系统的学习情况评价,提升教育培养质量。     

应用DOPS评价翻转课堂结合TBL在眼科实习教学中的效果

目的:应用临床操作技能直接观察评估(DOPS)探索翻转课堂结合小组合作学习(TBL)在眼科实习教学中的效果。方法:自2021-06-15/11-14在眼科实习的临床医学“5+3”一体化和临床医学五年制学生54人,分为传统教学组(A组)和翻转课堂结合TBL组(B组),通过DOPS评分比较A组、B组裂隙灯显微镜和直接眼底镜的教学效果,采用Mann-Whitney U检验进行统计分析。结果:A组学生裂隙灯显微镜DOPS总评分为59(58.00,60.00)分,B组学生总评分为63(61.00,65.00)分,A组评分显著低于B组(P<0.001)。A组学生直接眼底镜DOPS评分为63(61.00,63.75)分,B组评分为66(63.75,66.25)分,A组评分显著低于B组(P<0.001)。在“适应证、相关解剖结构的了解及操作步骤的熟练程度”“执行操作前的准备工作”“操作的技术能力”等方面,两项操作B组学生单项评分均显著高于A组(P<0.05)。结论:在眼科实习教学中采用翻转课堂结合TBL,较传统教学可以显著提升眼科实习生的临床操作技能水平。