人α2a干扰素酵母工程菌高产培养条件的研究

研究了摇瓶培养条件对人α2 a干扰素酵母工程菌生长及表达的影响 ,结果表明 ,当基础料中腺嘌呤含量为 2 0 μg/m L,在发酵进行至 1 2 h时再加入 2 0 μg/m L腺嘌呤时 ,IFN- α2 a生物活性及比活分别达到 7.3× 1 0 6IU/m L及 6.77× 1 0 7IU/mg。发酵过程中后期补入适量萄萄糖 ,且维持低糖水平 ,有利表达。维持总碳源含量不变 ,使培养基中葡萄糖与蔗糖的比例为 1∶ 0 .1 ,结果 IFN-α2 a生物活性及比活分别比对照增加了一倍以上。在发酵进行至 1 2 h时 ,加入 2 g/L谷氨酸 ,IFN-α2 a生物活性及比活分别比对照提高了 1 .76倍及 1 .94倍 ,而添加 0 .2 5～ 1 .0 g/L赖氨酸也能显著提高表达水平。培养基初始 p H对产物表达有较大影响 ,初始 p H为 6.5时 ,对表达最有利。利用上述摇瓶培养优化条件 ,在 2 .6L生物反应器中进行补料分批培养 ,人 α2 a干扰素生物活性达到 1 .3×1 0 7IU/m L ,为原工艺的 3倍。     

普鲁布考等药物对溶血磷脂酰胆碱引起的牛脑基底动脉条收缩的影响

目的 :研究溶血磷脂酰胆碱 (L PC)对牛脑基底动脉条收缩的影响及普罗布考等药物的保护作用。方法 :通过描记基底动脉条的张力变化 ,测定 L PC对基底动脉条收缩的影响。结果 :L PC能剂量依赖性 (1× 10 - 9～ 1× 10 - 5 mol/ L )促进基底动脉条收缩 ,在 1× 10 - 5 mol/ L时 ,收缩达最大 ,为 (15 1.0± 18.4) %。当用 Triton X- 10 0 (0 .1% )破坏血管内皮层后 ,L PC诱导的血管收缩作用消失。银杏叶提取物 (EGb)、普罗布考 (Pro)和维生素 E(Vit E)能剂量依赖性地减弱 L PC诱导的牛脑基底动脉条收缩。 结论 :药物 EGb,Pro和 Vit E能拮抗 L PC诱导的牛脑基底动脉条收缩。     

Short-Term Toxicity of Bitumen Upgrading Products in the Rat Following Repeated Dermal Exposure

Light gas oil (B-LGO), heavy gas oil No. 1 (B-HGOI), and heavygas oil No. 2 (B-HGOII) fractions of bitumen upgrading products(BUPs) were applied on the dorsal skin of rats at 25 mg/kg bw/day(low dose), 100 mg/kg bw/day (intermediate dose), and 400 mg/kgbw/day (high dose) for 4 weeks. Control animals received normalsaline while positive controls received a medium boiling coalliquefaction product (CLP) at 100 and 400 mg/kg bw/day. Reducedfood consumption and growth suppression were observed in malesand females treated with B-HGOI, B-HGOII, and CLP, but onlyin males receiving B-LGO. Increased relative spleen, kidney,and liver weights were observed in animals treated with B-HGOI,B-HGOII, and CLP, but not in control or LGO groups. A dose-relatedincrease in absolute and relative liver weight was most markedin animals receiving B-HGOII where a significant increase wasobserved starting at the low dose, followed by those receivingB-HGOI and CLP. Appearance of pale foci on the splenic capsuleand increases in spleen/body weight ratio were limited to animalsreceiving B-HGOI and B-HGOII. Decreases in hematocrit and RBCand increase in percentage of reticulocytes were observed inanimals of both sexes receiving B-HGOI and B-HGOII. Female ratsappeared to be more severely affected because significant decreasesin hemoglobin and RBC were observed in animals receiving thelow dose of B-HGOII and the intermediate dose of B-HGO-I. Increasedserum cholesterol was observed in B-HGOII-treated females atall dose levels, and in males starting at the intermediate dose.Histological changes were observed in the thymus gland, wheremoderate to marked cortical atrophy was noted in male and femalerats receiving the high dose of B-HGOI and B-HGOII, and in thebone marrow, where the most significant abnormality was thepresence of focal myelofibrosis in some male rats treated withB-HGOI and B-HGOII. Mild to moderate histological changes werefound in the thyroid, liver, and spleen of rats of all treatmentgroups. Changes in the skin included moderate hyperkeratosisin fe males receiving high doses of B-LGO and in animals ofboth sexes receiving high doses of B-HGOI, and moderate to markedepidermal hyperplasia in rats receiving high doses of B-HGOI.Based on these multiple endpoints, the severity of systemictox icity was B-HGOII > B-HGOI > CLP B-LGO. The NOEL wasabout 25 mg/kg bw/day for B-LGO and lower than 25 mg/ kg bw/dayfor B-HGOI and B-HGOII.     

Subchronic Toxicity of 3,3',4,4',5-Pentachlorobiphenyl in the Rat: I. Clinical, Biochemical, Hematological, and Histopathological Changes

The systemic, toxicity of 3,3',4,4',5-pentachlorobiphenyl (PCB126) following subchronic dietary exposure was investigatedin Sprague-Dawley rats. PCB 126 was administered to rats ofboth sexes at concentrations of 0.1, 1.0, 10, or 100 ppb intheir diet for 13 weeks. Another group of rats received a loadingdose of 5 µg PCB/kg body wt at the start of the feedingperiod followed by exposure to 10 ppb PCB diet for the sameperiod of time as the other groups. Growth suppression and decreasedfood consumption were observed in the highest dose groups ofboth sexes. Increased organ/body weight ratios for the liveroccurred in the 10 and 100 ppb groups of both sexes. Rats ofboth sexes exposed to the highest dose of the PCB also exhibitedincreased relative kidney, spleen, and brain weights. Hematologicaland most serum biochemical changes were confined to the 100ppb groups. These included elevated alkaline phosphatase, bilirubin,cholesterol, and aspartate aminotransferase, and decreased serumglucose, hemoglobin, erythrocytes, hematocrit, and platelets.A dose-dependent increase in liver ethoxyre-sorufin-O-deethylaseactivity was observed in rats of both sexes starting at 0.1ppb. A dose-dependent increase in liver uroporphyrin levelswas observed in both sexes and significant changes occurredin the female rats at 1.0 ppb and higher dose groups. Decreasedliver vitamin A was observed in the 10 ppb group and higherin both sexes. Kidney vitamin A was elevated in the 100 ppbgroup. No statistically significant changes were noted in concentrationsof brain biogenic amines. PCB 126 residues were 10-fold higherin liver than in fat. Treatment-related histopathological changeswere observed in the thymus, thyroid, bone marrow, and liverof rats exposed to the 10 ppb diet, but increased frequencyof mild changes was observed in most of these tissues at the1.0 ppb level. Based on the above data, the no adverse effectlevel was judged to be 0.1 ppb in the diet or 0.01 µg/kgbody wt/day.     

高度近视眼白内障手术疗效观察

目的　分析高度近视眼白内障手术效果。方法　高度近视合并白内障病例共１９１ 例（２７９ 只眼）,行白内障术后３ｍｏ以上,随访视力、眼屈光度及并发症,计算测量误差及ＳＲＫ－ＩＩ公式误差。结果　术后矫正视力０ ．５ 者２００ 只眼,占７１．７ ％ ;矫正视力＜ ０．１ 者１３ 只眼,占４ ．７ ％ － 眼轴越长,近视性眼底病变越重。术后发生视网膜脱离２ 只眼（０ ．７％） 。眼轴长度测量误差值平均为０．５３ｍｍ ,ＳＲＫ－ＩＩ公式计算的平均绝对屈光误差值为１．１２Ｄ。结论　高度近视眼白内障手术效果较一般人群差,且眼轴越长效果越差。     

局部药代动力学的药物浓度时空方程初探

目的 建立局部植入给药的药物浓度时空方程。方法 将局部药物浓度时空方程构建为空间分布函数和时间分布函数(药物浓度经时方程)的积函数。并以加权平均及多元分析的数学手段予以证明及推导。结果 四维时空的局部植入给药的药物浓度时空方程的通式为：C(t，X，Y，Z)＝F(X，Y，Z)．C(t)，F(X，Y，Z)＝B0 B1X B2Y B3Z B4r3 B5r2 B6r,C(t)＝A1e^-Ket A2e^-Ket A3c^-Ket.。两维变量的简化的药物浓度时空方程为：C(t,ρ)＝F(ρ)．C(t)F(ρ)＝D0 D1ρ D2ρ2 D3ρ3，C(t)同上。结论 推导基本合理，并在初步的动物试验探索中得以验证。理论有较好科研价值，有助于揭示局部给药的药代动力学规律。     

小剂量尿激酶与低分子肝素钙治疗不稳定性心绞痛

目的观察小剂量尿激酶+低分子肝素钙治疗不稳定性心绞痛(UAP)的临床疗效。方法将80例UAP患者随机分为尿激酶、低分子肝素钙组(A组)43例,尿激酶10万U溶于100ml生理盐水静脉滴注,连续12d,低分子肝素钙5000U皮下注射,1次/d,共12d;常规治疗组(B组)37例,硝酸甘油10mg溶于5%葡萄糖500ml静脉滴注,共12d,复方丹参20ml溶于5%葡萄糖200ml静脉滴注,共12d。观察两组治疗UAP总有效率及出血等不良反应的发生率,治疗前后测定血小板计数(BPC)、激活全血凝固时间(ACT)、纤维蛋白原定量(FB)。结果两组UAP治疗总有效率分别为88.4%和62.2%(P<0.05),轻微出血发生率两组间及治疗前后BPC、ACT、FB均无显著性差异(P>0.05)。结论小剂量尿激酶+低分子肝素钙治疗UAP疗效显著,且用药安全。     

甘糖酯对实验糖尿病大鼠粘附分子-CD54、CD106、CD62p的影响

目的观察糖尿病大鼠肾脏、主动脉等粘附分子的变化及甘糖酯干预的影响,为早期防治糖尿病并发症提供科学依据.方法实验分正常对照、糖尿病对照、高、低剂量甘糖酯共4组,通过免疫组织化学方法观察大鼠肾脏和主动脉CD54和/或CD106的表达,应用流式细胞仪测定血中单个核细胞表面CD54、血小板表面CI)62p的表达水平;应用甘糖酯治疗8周后,观察上述指标的变化.结果(1)血单个核细胞表面CD54测定表明高剂量甘糖酯组有明显降低,(CD54高=36.04±11.01%,VS CD54DM=65.09±14.92%,P＜0.05),而低剂量甘糖酯组降低不明显;甘糖酯时血小板表面CD62P表达影响不大;(2)肾脏和主动脉CD54、CD106免疫组化显示甘糖酯能降低其表达并减轻组织病理变化,且与剂量有关.(3)甘糖酯有降低血糖的作用,并与剂量有关(高剂量组BG治疗前=20.93土4.22mmol@L-1,BG治疗后=15.76±2.39mmol@L-1,P＜0.05;低剂量组BG治疗前=17.35±1.13mm0l@L-1,BG治疗后=13.52±6.24mmol@L-1,P＞0.05).结论糖尿病粘附分子的增加可能是糖尿病肾病和大血管病变的重要发病因素,甘糖酯可降低CD54、CD106对糖尿病并发症有延缓和改善作用.     

藻酸双酯钠注射液细菌内毒素检测

目的:建立藻酸双酯钠注射液的细菌内毒素检查法。方法:参照中国药典2000年版二部细菌内毒素检查法要求进行试验。结果:该药在 0.125g·L~(-1)下无干扰作用。结论:该药采用内毒素检查法进行检查是可行的。