地塞米松对犬视网膜超微结构的影响

目的：观察地塞米松对犬视网膜超微结构的影响。方法：取犬4只,右眼玻璃体和房水内注射盐水(为盐水组),左眼玻璃体和房水内注射地塞米松(为激素组),24h后处死,电镜观察视网膜超微结构有无改变,并与对照组进行比较。结果：盐水组和激素组与对照组比较视网膜超微结构无改变。结论：地塞米松对犬视网膜超微结构无影响。,Objective:To observe the influence of dexamethasone on dog＇s retina ul-trastructure. Methods:We injected normal saline into the vitreous body and aqueous humor ofthe right eyes while injecting dexamethasone into the left eyes in four dogs. After 24 hours, wekilled the dogs to observe ff their retina ultrastructure had altered, and compared with the re-sults of the control group. Results :In comparision with the control group,there was any changein retina ultrastructure in neither the normal saline group nor the hormone group. Conclusion:Dexamethasone has no influence on the retina uitrastructure of dogs.     

地塞米松·葡聚糖的合成及其肠内容物中的转释特性

目的　探讨地塞米松·葡聚糖 (平均相对分子质量 5× 10 5 )作为结肠定位地塞米松前体药物的可能性 .方法　以琥珀酸酐为交联剂 ,合成地塞米松前体药物 .将前体药物与大鼠胃肠道不同部位内容物一起孵育 ,检测地塞米松的释放情况 .结果　经高效液相色谱 (HPL C)分析 ,10 0 mg所合成的前体药物中载有地塞米松 9.2 mg.在 16 0 min的孵育时间内 ,前体药物在大鼠结肠及盲肠内容物中释放出地塞米松的量是其在小肠近端及小肠远端内容物中释放量的 2 .7倍 ,在胃内容物中无地塞米松的释放 .结论　地塞米松前体药物能在盲肠、结肠内容物中特异地释放出地塞米松 ,因此地塞米松·葡聚糖 (平均相对分子质量 5× 10 5 )可以作为结肠定位地塞米松前体药物 ,有选择性地将地塞米松运送到结肠     

地塞米松诱导幼龄大鼠胸腺细胞凋亡模型

目的：建立一个比较实用且成型时间短的地塞米松诱导大鼠胸腺细胞凋亡模型。方法：给幼龄大鼠（４周￣５周）腹腔注射地塞米松（０．０２ｇ／ｋｇ）采用形态学（光镜和电镜）、ＤＮＡ琼脂糖凝胶电泳、流式细胞光度分析等方法研究３、６、９、１５、２４ｈ等不同注射时间胸腺细胞凋亡变化。结果：在１５ｈ内,地塞米松诱导的大鼠胸腺细胞凋亡百分率随时间延长,凋亡发生率从６．２％逐渐增至５８．５％,注射地塞米松１５ｈ,在光镜和     

Inhibition of neutrophil and monocyte recruitment by endogenous and exogenous lipocortin 1

1. The role played by endogenous lipocortin 1 in the anti-migratory action exerted by dexamethasone (Dex) on monocyte recruitment in an in vivo model of acute inflammation was investigated by use of several neutralizing polyclonal antibodies raised against lipocortin 1 or a lipocortin 1-derived N-terminus peptide (peptide Ac2-26). The efficacy of peptide Ac2-26 in inhibiting monocyte and polymorphonuclear leucocyte (PMN) recruitment was also tested.
2. Intraperitoneal (i.p.) injection of zymosan A (1 mg) produced a time-dependent cell accumulation into mouse peritoneal cavities which followed a typical profile of acute inflammation: PMN influx was maximal at 4 h post-zymosan (between 15 and 20×10⁶ cells per mouse), and this was followed by an accumulation of monocytes which peaked at the 24 h time-point (between 10 and 15×10⁶ cells per mouse).
3. Dex administration to mice reduced zymosan-induced 4 h PMN infiltration and 24 h monocyte accumulation with similar efficacy: approximately 50% of inhibition of recruitment of both cell types was achieved at the dose of 30 μg per mouse (∼1 mg kg⁻¹, subcutaneously (s.c.)). Maximal inhibitions of 64% and 67% on PMN and monocyte recruitment, respectively, were measured after a dose of 100 μg per mouse (∼3 mg kg⁻¹, s.c.).
4. Dex (30 μg s.c.) inhibited monocyte (53%) and PMN (69%) accumulation in response to zymosan application in mice which had been treated with a non-immune sheep serum (50 μl s.c.). In contrast, the steroid was no longer active in reducing cell accumulation in mice which had been passively immunized against full length human recombinant lipocortin 1 (serum LCS3), or against lipocortin 1 N-terminus peptide.
5. Treatment of mice with vinblastine (1 mg kg⁻¹, intravenously (i.v.)) produced a remarkable leucopenia as assessed 24 h after administration. This was accompanied by a 60% reduction in 4 h-PMN influx, and by a 27% reduction in 24 h-monocyte accumulation, measured after zymosan administration. The inhibitory effect of Dex on monocyte recruitment was not significantly modified in vinblastine-treated mice, with 36% and 57% of inhibition calculated at the dose of 30 μg Dex, and 70% and 60% of inhibition at 100 μg Dex, in vehicle- and vinblastine-treated mice, respectively.
6. Treatment of mice with peptide Ac2-26 dose-dependently attenuated PMN influx at 4 h post-zymosan with a significant effect at 100 μg per mouse (45% of inhibition, n=9, P<0.05) and a maximal effect of 61% inhibition at the highest dose tested of 200 μg s.c. (n=14, P<0.05). No effect of peptide Ac2-26 (200 μg s.c.) was seen on zymosan-induced 24 h monocyte recruitment. In contrast, administration of 200 μg peptide Ac2-26 every 6 h was effective in reducing the number of monocytes harvested from the inflamed peritoneal cavities at 24 h post-zymosan: 9.40±0.58×10⁶ monocytes per mouse (n=13) and 5.74±0.34 monocytes per mouse (n=14) in vehicle- and peptide Ac2-26-treated mice, respectively (P<0.05).
7. Finally, peptide Ac2-26 produced a concentration-dependent inhibition of the rate of phagocytosis of mouse resident peritoneal macrophages as measured by flow cytometry, with a maximal reduction of 34% at the highest concentration tested of 100 μg ml⁻¹ (n=8 experiments performed in duplicate; P<0.05).
8. In conclusion, this study suggests that in vivo monocyte recruitment during acute inflammation is, at least in part, under the negative modulatory control of endogenous lipocortin 1 (as seen after administration of Dex by using the specific antisera) and exogenous lipocortin 1 mimetics (as observed with peptide Ac2-26). In addition to the neutrophil, we can now propose that the monocyte also can be a target for the in vivo anti-inflammatory action of lipocortin 1.

     

Dexamethasone effects on cerebral protein synthesis prior to and following hypoxia-ischemia in immature rat

We hypothesized that the neuroprotection against cerebral hypoxic-ischemic damage observed with dexamethasone treatment in immature rats is related to a change in cerebral protein synthesis. Six-day-old Wistar rats were injected with either vehicle (10 ml/kg) or dexamethasone (0.1 mg/kg) 24 h prior to cerebral hypoxia-ischemia. Local cerebral protein synthesis (incorporation of 14C-leucine into proteins) was measured in 7-day-old rats during normoxia, during hypoxia-ischemia, and after hypoxia-ischemia which was produced with right carotid artery ligation and 2-h exposure to 8% O2. In normoxic controls, cerebral protein synthesis was similar in dexamethasone and vehicle-treated animals. During hypoxia-ischemia, local cerebral protein synthesis decreased markedly (p < 0.0001) in ischemic regions ipsilateral to the occlusion, irrespective of treatment. After hypoxia-ischemia, protein synthesis declined even further in vehicle-treated animals. Reductions in protein synthesis were substantially more severe in vehicle- than dexamethasone-treated animals, particularly after hypoxia-ischemia (p < 0.0001). Thus, neuroprotection with dexamethasone is not related to a reduction in basal levels of cerebral protein synthesis, but is associated with an improved protein synthesis during and following hypoxia-ischemia.     

平阳霉素联合地塞米松治疗颌面部大面积海绵状血管瘤

目的：观察平阳霉素（ＰＹＭ）联合地塞米松（ＤＸＭ）治疗颌面部大面积海绵状血管瘤的临床疗效和不良反应。方法：对９例临床确诊的颌面部范围６ｃｍ×７ｃｍ～１０ｃｍ×１２ｃｍ之间的大面积海绵状血管瘤,采用每周１次多点多方向瘤腔内注射药物,比较治疗前后患者的反应和肿瘤的形成变化。结果：全部病例肿瘤消失,无明显不良反应,经８个月～４６个月观察,临床治愈率为１００％。结论：ＰＹＭ联合ＤＸＭ能够治愈颌面部大面积海绵状血管瘤,具有完整保存组织正常形态和功能的特点,克服了单独使用ＰＹＭ带来的不良反应,提示两药在治疗上有协同作用。     

Molecular Motion of Drugs in Hydrocolloids Measured by Electron Paramagnetic Resonance

The effects of a polymer, the Li-salt copolymer of methyl-methacrylic acid, and its methyl ester on the motion of drug molecules in hydrocolloids were studied. The investigation was carried out by means of electron paramagnetic resonance (EPR) using the model nitroxide tempol, and the spin-labeled drugs lidocaine (si-lid) and dexamethasone (sl-dex). Synthesis of sl-dex was performed. Spin-labeled molecules dissolved in hydrocolloids undergo a fast reorientation motion. The decreasing order of rotational correlation times () —sl-dex > si-lid > tempol—suggests that the size and the shape of the molecules strongly affect their motion. The inhibition of motion of larger molecules depends also on their flexibility. The values indicate proportionality of the microviscosity of hydrocolloids to the polymer concentration. Rotational motion is dependent on the local environment conditioned by the free spaces between polymer molecules.     

醋酸地塞米松片含量均匀度紫外测定波长偏离原因考察

目的　寻找醋酸地塞米松片含量均匀度测定时紫外波长偏离的原因。方法　用紫外分光光度法测定含量均匀度测定液的最大吸收波长值 ,对超出药典规定范围的测定液用高效液相色谱法分离 ,观察有无杂质出现。色谱柱为Elit testODS柱 (2 4 0mm× 4 6mm) ,流动相 :甲醇 -水 (70∶30 ) ,检测波长 2 4 0nm。同时用离心法考察辅料对波长偏离的影响。结果　主药中含有的杂质和辅料使醋酸地塞米松片含量均匀度紫外测定波长偏离。结论　用HPLC测定醋酸地塞米松片含量均匀度可避开波长偏离的干扰 ,使结果准确     

火把花根片对哮喘大鼠气管平滑肌细胞L型钙通道的作用

目的　探讨火把花根片对哮喘大鼠气管平滑肌细胞L型钙通道 [L typecalcium (L LCa)channel]的作用。方法　将♂Wistar大鼠分为正常对照组、哮喘组、火把花根片(Huobahuagentablet,HBT)治疗组及地塞米松 (dexametha sone,DXM )治疗组共 4组 ,分别给予相应的处理 ,观测大鼠支气管平滑肌细胞L LCa在正常时 ,哮喘发作时 ,以及给予HBT及DXM治疗后的变化。结果　火把花根片治疗后的哮喘大鼠的L LCa与哮喘组以及正常对照组大鼠通道开放概率相比差异均有显著性 (P <0 0 5 )。哮喘组通道L LCa开放时间常数 (τO1和τO2 )延长 ,关闭时间常数 (τc1和τc2 )缩短 ,与正常对照组相比差异有显著性 (P <0 0 5 )。火把花根片与地塞米松治疗后的哮喘大鼠的L LCa与哮喘组相比通道开放时间常数缩短 ,关闭时间常数延长。结论　哮喘大鼠L LCa的活动明显增强。经火把花根片治疗后L LCa活动有所减弱 ,表现为通道开放时间常数缩短 ,关闭时间常数延长。提示火把花根片与地塞米松均可明显抑制哮喘大鼠的L LCa的活动 ;HBT与DXM均可逆转哮喘大鼠L LCa动力学的改变。