The membrane potential of vascular smooth muscle appears to modulate uptake2 of 3H-isoprenaline

Summary Segments of the rabbit main pulmonary artery and of its two branches were exposed for 10 min to 50 nmol/l ³H-(±)-isoprenaline, and the accumulation of tritium in the tissue was determined; COMT was inhibited in all experiments. 1. The accumulation of the tritium label was sensitive to 3-O-methyl-isoprenaline (OMI), showing that this vascular smooth muscle possesses uptake₂. 2. In the presence of 0.01 to 1 mol/l (–)-noradrenaline, the accumulation of tritium was depressed (in a concentration-dependent manner). This decline involved the OMI-sensitive accumulation of ³H-isoprenaline. 3. The presence of any one of three selective alpha₁-adrenoceptor antagonists (1 gmol/l prazosin, 1 mol/l WB4101, 10 gmol/l corynanthine) prevented the effect of 1 mol/l (–)-noradrenaline on the accumulation of tritium. However, in the absence of (–)-noradrenaline, the three antagonists failed to affect the accumulation of tritium. 4. 10 mol/l nicorandil caused the accumulation of tritium to increase. 5. As stimulation of alpha₁-adrenoceptors is known to result in depolarization, and as nicorandil is known to hyperpolarize this smooth muscle, it is concluded that the resting membrane potential modulates uptake₂. Send offprint requests to U. Trendelenburg at the above address     

Prostaglandins: Antiproliferative effect of PGD 2 on cultured human glioma cells

Summary Five cultured human glioma cell lines were investigated for their reaction to prostaglandin (PG) D 2 and E 2. In all cases a suppressive effect on DNA synthesis as assessed by³H-thymidine incorporation was seen with all test substances as early as six hours after the addition of the compounds in doses of usually 10^–5 M. A dose response curve was generated in four cases and showed an estimated ED 50 of about 5 · 10^–6 M. The effect was most pronounced at 12 hours after which the cultures began to recover except those which had been incubated with PGD 2. In those cultures which had been exposed to PGD 2 virtually no thymidine incorporation was seen after 24 hours and as long as 72 hours.In another set of experiments, the effect of PGD 2, PGE 2, two synthetic PGD 2 analogues, with a chlorine substitution in position 9 (DACl) or with a fluoride substitution in position 9 (DAF) and a synthetic prostacyclin-analogue (Iloprost) was investigated after single and repeated addition of the compounds. A second administration after 12 hours of incubation did not result in a further decrease in³H-thymidine incorporation like that observed during that first incubation period. In general the cells recovered after 24 hours total incubation time except those which had received PGD 2 or repeated doses of PGE 2. Only in those cells which had been treated with PGD 2, an almost complete blockade of³H-thymidine incorporation was seen even after the single administration. Parallel evaluation of the cells by flow cytometry showed effects on cell cycle distribution at different times of the incubation. After 12 hours cells began to accumulate in G2/M at levels of approximately twice control, the effect being the least pronounced for PGD 2. For this compound we observed a threefold increase in cells in the S phase. After 24 hours the cell cycle distribution had normalized for all compounds except PGD 2 where the arrest of cells in G2/M persisted to be about 2–3-fold control level until the end of the experiment.Our data suggest, that also in cultured human glioma cells, prostaglandins are effective in suppressing cellular DNA synthesis.Although the effect of PGD 2 can be achieved to some extent by PGE 2 and the analogues which are more stable to dehydrogenases and the metabolic conversion into other biologically active homologues, PGD 2 appears to have a unique quality of action, becoming apparent 24 hours after administration.Abbreviations PG prostaglandin - DME Dulbecco's modified Eagle medium - STV trypsin in phosphate buffered saline EDTA (versene) - PBS phosphate buffered saline - ICP impulse cytophotometry - TCA trichloroacetic acid - DACl 9-chloro-15-cyclohexyl-11,15-dihydroxypentanor-5,13-prostadienoic acid- and DAF=9-Fluoro-15-cyclohexyl-11,15-dihydroxypentanor-5,13-prostadienoic acid Dedicated to Prof. Dr. Friedrich Loew on the occasion of his 65th birthday and the 25th anniversary of the Homburg Neurosurgical University Clinic, which has been founded and built up by him.     

Cervical tissue uptake of all-trans-retinoic acid delivered via a collagen sponge-cervical cap delivery device in patients with cervical dysplasia

The present study was undertaken to evaluate the systemic absorption and cervical tissue uptake of all-transretinoic acid (TRA), delivered via a collagen spongecervical cap delivery device in patients with intraepithelial cervical dysplasia. Ten patients with histologically proven mild or moderate cervical dysplasia were included in this pharmacologic study. The two TRA concentrations (0.05% and 0.372%) selected for study represent the starting and maximally tolerated doses used in phase I clinical trial. All-trans-retinoic-11-³H acid (³H-TRA, 500 Ci) was used to facilitate cervical tissue uptake studies. Cervical biopsies and post-treatment blood samples were obtained from each patient after TRA exposure. The uptake of TRA into cervical tissues four hours after drug administration was significantly increased at the maximally tolerated TRA dose. There was a rapid decrease in cervical tissue concentration of TRA at the 0.372% dose between 4 and 24 h after drug exposure, suggesting a relatively short elimination half-life of TRA in cervical tissues. HPLC analysis of post-treatment blood samples indicate that there was no systemic absorption of TRA after local cervical administration.     

Effects of antidepressants on the uptake and release of norepinephrine from rat cerebral cortex

The effects of several antidepressants on the release of (³H)-norepinephrine (NE) from homogenates of rat cerebral cortex were studied. A continuous superfusion collection system was used in order to differentiate these effects from effects on reuptake. Amitriptyline, maprotiline, mianserin, and trazodone produced a statistically significant decrease in spontaneous tritium efflux when present in the superfusion medium at a concentration of 1.0 M. The other antidepressants studied had no effect. We used a buffer with the K⁺ concentration raised to 56 mM as a model of depolarization-induced release. Desipramine, fluoxetine, and iprindole (again at 1.0 M) caused a significant decrease in this measure. These results indicate that some of both the tricyclic and atypical antidepressants may alter spontaneous or depolarization-induced release of NE.This work was supported in part by a grant from the Pharmaceutical Manufactures Association Foundation-Medical Student Research Fellowship     

In vitro H-serotonin (5-HT) synthesis and release in BALBc and C57BL mice. I. Terminal areas

"In vitro," 3H-5-HT and 3H-5-HIAA newly synthesized from 3H-TRP are measured in the caudate nucleus and the hippocampus of C57BL and BALBc mice. Higher synthesis, utilization and release are to be found in C57BL than in BALBc strain. In the hippocampus of C57BL this higher synthesis is due both to higher tryptophan hydroxylase activity and to higher tryptophan uptake ability. But in the caudate nucleus the initial accumulation of tryptophan is similar in both strains. Finally the two forms of monoamine oxidase (A and B) show also similar activities in both strain. These data will be compared to those obtained at the nerve cell body level in the paper (II).     

硒补充剂对妊娠期糖尿病患者血糖和血脂代谢及妊娠结局的影响分析

目的探讨硒补充剂对妊娠期糖尿病患者血糖、血脂代谢和妊娠结局的影响。方法将2018年7月-2019年6月盘锦市中心医院收治的45例妊娠期糖尿病患者随机分为对照组21例和硒酵母组24例。两组患者均给予健康教育、饮食指导、运动指导等常规治疗,硒酵母组在常规治疗基础上给予硒酵母片治疗。比较两组治疗前后空腹血糖、胰岛素抵抗指数、总胆固醇、甘油三酯、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇水平及妊娠结局。结果治疗后两组空腹血糖和胰岛素抵抗指数均较治疗前下降,且硒酵母组两项指标均低于对照组,差异均具有统计学意义(P<0.05)。治疗后两组孕妇总胆固醇、甘油三酯、低密度脂蛋白胆固醇水平较治疗前下降,且硒酵母组三项指标水平低于对照组,差异均具有统计学意义(P<0.05)。治疗后硒酵母组高密度脂蛋白胆固醇水平高于治疗前,差异具有统计学意义(P<0.05)。对照组治疗前后以及两组治疗后高密度脂蛋白胆固醇水平差异均无统计学意义(P>0.05)。硒酵母组新生儿高胆红素血症发生率和新生儿住院率均低于对照组,差异均具有统计学意义(P<0.05)。两组其他不良妊娠结局差异均无统计学意义(P>0.05)。结论硒补充剂能够进一步改善妊娠期糖尿病患者的血糖和血脂代谢,同时,也能降低新生儿高胆红素血症发生率和住院率,值得推广使用。     

妊娠期糖尿病患者产后糖代谢异常转归影响因素分析

目的探讨妊娠期糖尿病(GDM)患者产后糖代谢异常(AGM)转归及其影响因素。方法选择2019年1月至12月,于四川大学华西第二医院孕期被诊断为GDM,并于产后4~12周进行75 g口服葡萄糖耐量试验(OGTT)筛查的1175例单胎妊娠产妇为研究对象。根据其产后糖代谢是否正常,将其分为研究组(n=361,产后AGM者)与对照组(n=814,产后糖代谢正常者)。采用回顾性分析方法,收集受试者一般临床资料及孕期与产后4~12周75 g OGTT结果等,并采用成组t检验或χ^(2)检验进行统计学分析。对GDM患者产后AGM转归相关影响因素进行单因素分析与多因素非条件logistic回归分析,探讨其AGM转归的独立影响因素。本研究遵循的程序符合病例收集医院伦理委员会制定的伦理学标准,得到该伦理委员会批准[审批文号:医学科研2021伦审批第(181)号]。结果①24~28孕周时,1175例GDM患者75 g OGTT结果提示,空腹血糖(FPG)及OGTT 1、2 h血糖指标中,1、2、3项升高者分别为639例(54.4%)、373例(31.7%)与163例(13.9%)。②产后4~12周时,1175例GDM患者75 g OGTT结果提示,产后糖代谢正常者为814例(69.3%),AGM为361例(30.7%),包括空腹血糖受损(IFG)为19例(1.6%),糖耐量受损(IGT)为294例(25.0%),IFG+IGT为23例(2.0%),疑似2型糖尿病(T2DM)患者为25例(2.1%)。③产后AGM转归影响因素的单因素分析结果显示,研究组GDM患者年龄、糖尿病家族史发生率,24~28孕周OGTT 1、2 h血糖值,以及2项血糖指标(OGTT 1、2 h血糖)均升高与3项血糖指标(FPG及OGTT1、2 h血糖)均升高者所占比例,均显著高于对照组,而研究组仅1项血糖指标(FPG或OGTT 1 h血糖)升高者所占比例,则显著低于对照组,2组比较,差异均有统计学意义(P<0.05)。④多因素非条件logistic回归分析结果:模型1将受试者年龄、糖尿病家族史及24~28孕周OGTT 1、2 h血糖值进行多因素logistic回归分析结果显示,糖尿病家族史及24~28孕周OGTT 1、2 h血糖值,均为GDM患者产后AGM转归的独立危险因素(OR=1.693、1.205、1.355,95%CI:1.208~2.373、1.088~1.335、1.204~1.524,P=0.002、<0.001、<0.001)。模型2将受试者年龄、糖尿病家族史、24~28孕周OGTT血糖指标升高项目进行多因素logistic回归分析结果显示,糖尿病家族史及24~28孕周OGTT 2项血糖指标(OGTT 1、2 h血糖)升高与3项血糖指标均升高,均为GDM患者产后AGM转归独立危险因素(OR=1.668、1.421、1.747,95%CI:1.192~2.333、1.035~1.952、1.195~2.553,P=0.003、0.030、0.004);24~28孕周仅FPG或OGTT 1 h血糖升高为其独立保护因素(OR=0.401、0.646,95%CI:0.240~0.670、0.418~0.997,P<0.001、=0.048)。结论对于GDM患者产后AGM转归,临床应关注其年龄、糖尿病家族史、孕期OGTT结果等指标。对GDM高危人群进行上述指标持续监测与规范干预,是健全GDM孕前-孕期-产后全程管理的重要环节。     

救脑宁注射液对培养神经细胞缺氧缺糖损伤的保护作用

为了探索“救脑宁”注射液对中风病的疗效机理 ,将原代培养 8～ 12d的新生大鼠皮层神经细胞进行缺氧缺糖处理 ,观察该药对缺氧缺糖损伤神经细胞的影响。结果表明 :缺氧缺糖组细胞上清液中丙二醛 (MDA)含量、乳酸脱氢酶 (LDH)活性较对照组显著升高 ,细胞超氧化物岐化酶 (SOD)活性和细胞生存率则显著降低 ,救脑宁组MDA、LDH显著低于缺氧缺糖组 ,而SOD活性及细胞生存率则高于缺氧缺糖组 (P <0 0 1)。因此 ,抗脂质过氧化损伤、提高神经细胞对缺氧缺糖的耐受性 ,可能是其疗效机理之一。     

妊娠期糖尿病血糖控制水平与妊娠结局的关系

目的探讨妊娠期糖尿病孕妇血糖控制水平与妊娠结局的关系.方法对60例妊娠期糖尿病(gestational diabetes mellitus,GDM)和47例糖耐量损害(impaired glucose