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.     

Evaluation of the sites of opioid influence on anterior pituitary hormone secretion using a quaternary opiate antagonist.

Studies were conducted to determine the effects of a potent narcotic antagonist, nalmefene methyliodide, which does not cross the blood-brain barrier (BBB), on the secretion of anterior pituitary hormones and on the anterior pituitary hormonal response to morphine sulfate. Since the localization of opiate receptor responses to inside or outside the BBB depended upon the relative ability of nalmefene HCl and nalmefene methyliodide to penetrate the BBB, initial studies were conducted to document that nalmefene methyliodide does not block opiate receptors inside the central nervous system. While nalmefene HCl blocked morphine-induced antinociceptive responses at doses as low as 10 micrograms/kg, nalmefene methyliodide was ineffective in this regard at doses as high as 500 micrograms/kg. The luteinizing hormone (LH) suppression and prolactin (PRL) secretion induced by morphine was blocked by both nalmefene HCl and its methyliodide analogue, indicating that the opioid receptor type which mediates both responses is located outside the BBB. We observed that basal PRL levels were reduced by nalmefene HCl but not by nalmefene methyliodide indicating that basal PRL secretion is influenced by opioid neurons inside the BBB. While nalmefene HCl blocked morphine-induced suppression of thyroid-stimulating hormone (TSH) release, nalmefene methyliodide was less effective, suggesting that opiate-induced TSH suppression may be mediated by receptors located both within and outside the BBB. Nalmefene HCl caused a growth hormone (GH)-secretory response by itself, but nalmefene HCl and nalmefene methyliodide were ineffective in blocking morphine-induced GH secretion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Changes in the molecular structure of mouse fetal astrocyte nucleosomes produced in vitro by methylmercuric chloride

The fluorescent probe N-(3-pyrene)maleimide, which specifically labels the cysteine residues of histone H3 within the nucleosome, was used to monitor changes in the nucleosomal structure of mouse fetal astrocytes exposed to varying concentrations of methylmercuric chloride. Methylmercuric chloride treatment (10 microM) for 6 hr produced a significant decrease in the degree of fluorescence of the probe. The decrease was much smaller following a 4-hr incubation period. These results correlate with recent observations showing that significant changes in the thymidine labeling index occur following 4-6 hr of exposure to methylmercury (MeHg). It is hypothesized that MeHg enters the cells during the growth phase and attaches to the protein moiety of the nucleosome in or near the cysteine groups of histone H3, thus diminishing the binding capacity of the fluorescent probe. Addition of a detergent (sodium dodecyl sulfate) resulted in only a small increase in the degree of fluorescence of the treated nucleosomes as compared to controls, showing that the interaction of MeHg with the nuclear proteins was not dissociated by detergent. In view of the strong interaction between DNA and the histone dimer H3-H4 and the potential importance of the latter in gene regulation, these results suggest an additional means by which MeHg may exert its toxic effects.     

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。     

The interaction of platinum antitumour drugs with mouse liver mitochondria.

A study was undertaken to determine if cis-DDP and its second generation derivatives produced effects on mouse liver mitochondria, and if any of the observed effects could be correlated with the nephrotoxicity of the drugs. Although changes were observed in mitochondrial morphology, enzyme activity, Ca2+ influx, terbium binding and surface potential, no specific effect was correlated with nephrotoxicity. cis-DDP produced marked changes in mitochondrial morphology; electron probe analysis showed binding of the drug to the mitochondria. Inhibition of complex I and II activity of the respiratory chain and an ionic-strength-dependent effect on Tb3+ (a Ca2+ analogue) fluorescence were observed. The non-nephrotoxic derivatives, CHIP and tetraplatin, also produced significant changes in morphology. Treatment with these derivatives also produced decreases in mitochondrial enzyme activity, but the effect on terbium binding had an ionic-strength dependence which was inverse to that observed with cis-DDP. The tetravalent compounds also had a notable effect on mitochondrial surface potential. Carboplatin had an effect on morphology and Ca2+ influx and it inhibited the respiratory enzymes, although in a manner different from that observed with cis-DDP. Carboplatin had a minimal effect on terbium binding. It is evident that if the platinum drugs enter a cell to exert their action at the nuclear level, they will also depress mitochondrial function. The observed effects did not correlate with nephrotoxicity but, since all four compounds significantly altered mitochondrial structure and function, they may be related to the cytotoxicity of the drug.     

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。