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 selective actions of dopamine D-1 and D-2 receptor agonists and antagonists on opioid antinociception

The effect of the selective dopamine receptor agonists SKF 38393 (D-1) and quinpirole (D-2) on nociception was studied in the mouse tail immersion test. The D-1 receptor agonist induced mild hyperalgesia whereas the D-2 agonist produced antinociception. Pretreatment with either the selective D-1 receptor antagonist SCH 23390 or the D-2 receptor antagonist (-)-sulpiride converted the hyperalgesia produced by the D-1 agonist into an antinociceptive response whereas the effect of the D-2 receptor agonist was significantly antagonised. The antinociceptive response of selective opioid agonists was also studied in combination with selective dopamine receptor agonists and antagonists. Sufentanil (mu-opioid) antinociception was enhanced in animals pretreated with (-)-sulpiride but not SCH 23390. In animals co-administered sufentanil with SKF 38393 there was a reduced antinociceptive effect whilst quinpirole enhanced the action of sufentanil. Likewise, antinociception induced by the kappa-opioid agonist U50,488H was unaltered in animals pretreated with SCH 23390, increased by (-)-sulpiride, and reduced by SKF 38393. delta-Opioid antinociception induced by [D-Ala2,D-Leu5]enkephaline remained unmodified following pretreatment with either (-)-sulpiride or SCH 23390 but was potentiated in animals which received both the delta-agonist and the D-2 receptor agonist. It is concluded that D-2 receptor agonists not only have intrinsic antinociceptive activity, but can also potentiate opioid-induced antinociception. Similarly, dopamine D-2 receptor antagonists appear to potentiate opioid-induced antinociception in this nociceptive model.     

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。     

Atrophoderma of Pasini and Pierini. An immunopathologic case study.

Atrophoderma of Pasini and Pierini (APP) is a rare and distinctive form of dermal atrophy of uncertain origin. In only one previous report have immunopathologic methods been used to study a case of atrophoderma of Pasini and Pierini, and on the basis of the results obtained it was concluded that immunologic mechanisms were relevant to the pathogenesis of the condition. A detailed investigation of a case of atrophoderma of Pasini and Pierini was conducted using immunofluorescence and immunoperoxidase techniques. The epidermal Langerhans cells were abundant and expressed polyclonal immunoglobulin M on the cell-surface membrane. Biopsy of the same lesion was repeated 6 months later and revealed staining for immunoglobulins A and M and also for C3. This pattern of staining could not be reproduced in a range of other atrophic or scarring cutaneous lesions. Immunophenotypic analysis of the mild perivascular mononuclear cell infiltrate revealed an aberrant T-cell phenotype of uncertain significance.     

Comparison of the inhibitory action of aminobeclamide and beclamide on socially offensive behaviour

The inhibitory effects of aminobeclamide (N-(p-aminobenzyl)-beta-chloropropionamide) on socially offensive behaviour has been studied and compared with those of the parent drug beclamide (N-benzyl-beta-chloropropionamide). Following oral administration in mice which had been individually housed for a 28 day period then paired with normal group-housed opponents, aminobeclamide and beclamide both produced significant and dose-related inhibition of socially offensive behaviour. Aminobeclamide (20-150 mg kg-1 p.o.) and beclamide (50-250 mg kg-1 p.o.) gave increased offense onset latency whilst at the same time they reduced the incidence of offense encounters/animal and decreased the group percentage of animals displaying offense behaviour. It is likely that both drugs have similar monoamine modifying effects though this animal study suggests that aminobeclamide is 1.5 to 2.7 times more potent than beclamide against socially offensive behaviour.     

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。     

Optimizing Suicide Gene Therapy for Head and Neck Cancer

An effective “suicide gene” therapy strategy in experimental studies has been the use of the herpes simplex virus thymidine kinase gene(HSV-tk) to sensitize tumors to the cytotoxic effects of ganciclovir administration. Previous studies using this model have focused on utilizing maximal viral titers and high levels of ganciclovir that are not compatible with human dosing. Because of the high ganciclovir doses and the maximal viral titers, this strategy has limited application to actual clinical scenarios. In the following studies the authors investigate tumor regression in an oral squamous cell carcinoma animal model as a function of variable adenoviral titers and more physiologic ganciclovir dosing. Using adenoviral titers ranging from 1 × 10⁸ to 2 × 10⁹ plaque forming units(pfu) to treat oral tumors, they found no statistical difference in tumor regression among the different viral doses, despite differences in mitotic activity. Each treatment group, however, demonstrated a significant effect on tumor regression when compared with controls. Furthermore, the authors were able to reduce the level of ganciclovir administration to 10 mg/kg twice daily from established levels of 100 to 150 mg/kg twice daily while maintaining significant tumor responses to the HSV-tk therapy. Mean survival of animals treated with this lower ganciclovir dose was significantly higher than in controls and was equal to established means based on previous studies using higher ganciclovir doses. The optimization of this suicide gene therapy strategy is imperative in order to minimize theoretical and known viral and ganciclovir toxicities while establishing a foundation upon which to design appropriate and effective clinical trials.