Release of [3H]norepinephrine: alteration by early developmental exposure to diazepam

The effect of prenatal exposure to diazepam (over gestational days 13-20) on the release of tritiated norepinephrine [( 3H]NE) from selected brain regions was analyzed to determine mechanisms whereby such exposure could disrupt functioning in specific NE neurons, as previously observed. Pregnant rats were administered diazepam (DZ) once daily at doses of 1.0, 2.5 or 10.0 mg/kg and the offspring studied as adults at 70-90 days of age and during development at 14, 21, 35 and 56 days of age. Release of [3H]NE was measured during in vitro incubation using 25 mM potassium as the depolarizing stimulus. As noted previously, prenatal exposure to DZ induced an effect only on NE neurons innervating the hypothalamus, sparing the NE innervation to the hippocampus and cerebellum. Prenatal exposure to DZ had no effect on the depolarized release of [3H]NE in the hypothalamus until after 35 days of age, a developmental pattern previously observed with respect to endogenous NE levels. In adult rat offspring, however, the depolarization-induced release of [3H]NE from the hypothalamus decreased 28%, 32% and 64% (relative to uninjected control values) in animals prenatally exposed to DZ at 1.0, 2.5 or 10 mg/kg/day respectively. Concurrent exposure of the pregnant dam to benzodiazepine antagonists (Ro 15-1788 or ethyl-beta-carboline-3-carboxylate) prevented the effects of DZ (2.5 mg/kg/day) on [3H]NE release, demonstrating again the importance of the benzodiazepine binding site to the effects induced by the early DZ exposure. The initial accumulation of the [3H]NE was not altered by the prenatal exposure.(ABSTRACT TRUNCATED AT 250 WORDS)     

CONGENITAL DISLOCATION OF THE KNEE AS A CONSEQUENCE OF PERSISTENT AMNIOTIC FLUID LEAKAGE

SUMMARY A case congenital dislocation of both knees and dislocation of the left hip in an infant whose mother had a chronic amniotic fluid leakage after mid-trimester amniocentesis.     

高效液相色谱法测定右旋儿茶素血浆浓度及药代动力学参数

本文建立了体液中右旋儿茶素的RP-HPLC测定方法。采用C_(18)键合相硅胶为填料的固相提取柱进行样品预处理,右旋儿茶素的提取回收率为79.8%.应用二极管阵列检测器对色谱峰纯度进行鉴定。该法精密度好,方法回收率近100%,日内、日间的变异系数为2.4～5.6%,血浓69.6～1160 ng/ml范围内呈线性关系,r=0.9993。家兔静注右旋儿茶素18mg/kg,其药代动力学过程符合二室模型,分布相半衰期为0.129 h,消除相半衰期为1.19h。     

石杉碱甲类似物的研究II.N-甲基吡啶酮石杉碱甲类似物的合成

石杉碱甲(1)是从中草药石杉属植物千层塔(Lycopodium serratum Thunb.)中分得的一种高效可逆的乙酰胆碱酯酶抑制剂,临床试验证实它对早老性痴呆症有显著疗效。本文报道N-甲基吡啶酮石杉碱甲类似物2和3的合成。2-甲氧基-5-甲氧羰基-11-亚甲基-5,9-甲撑环辛-7-烯并吡啶(9)在乙腈中用三甲基氯硅烷和碘化钠选择性脱保护以定量的产率得吡啶酮10,再用甲醇钠和碘甲烷甲基化得N-甲基吡啶酮11,11经碱性水解,Curtius重排和氨基的脱保护得N-甲基吡啶酮石杉碱甲类似物2。通过类似的途径从中间体2-甲氧基-5-甲氧羰基-7-甲基-11-酮-5,9-甲撑环辛-7-烯并吡啶(14)合成了类似物3。类似物2和3的乙酰胆碱酯酶抑制活性均低于天然石杉碱甲。     

Carboxylic acid replacement structure-activity relationships in suosan type sweeteners. A sweet taste antagonist. 1.

N-(4-Cyanophenyl)-N'-(2-carboxyethyl)urea (2), an analogue of suosan [1,N-(4-nitrophenyl)-N'-(2-carboxyethyl)urea], is a known high-potency sweetener derived from beta-alanine. Sulfonic and phosphonic acid analogues of 2 were prepared to develop structure-activity relationships through modification of the carboxylic acid region of this family of sweeteners. Neither of the carboxylic acid replacements resulted in sweet analogues. However, we found that N-(4-cyanophenyl)-N'-[(sodiosulfo)methyl]urea (7) is an antagonist of the sweet taste response. The bitter taste response to caffeine, quinine, and naringin was also antagonized. Antagonist 7 was found to inhibit the sweet taste perception of a variety of sweeteners. Antagonist 7 had no effect on the sour or salty taste response.