2005～2007年我国非甾体抗炎药市场应用分析

目的：以骨骼肌肉系统使用非甾体抗炎药物为例，分析该类药物在2005～2007年的销售数量、销售金额及生产厂家风云榜。方法：采用药物分类累加的方法统计2005～2007年非甾体抗炎药的销售数量和金额排序，并对前10位药品销售数量和金额对比，及前10位厂家对比。结果：双氯芬酸稳居销售榜首，美洛昔康、布洛芬等药物位居其后。结论：新一代的非甾体抗炎药已经占据主要市场，各类药物各有特色，但是仍需注意其消化系统及心血管系统的不良反应。     

慢性乙型病毒性肝炎治疗新方法

就当前慢性乙肝治疗的新方法、新进展作一综述。     

派立明与贝特舒联合应用对降眼压的临床观察

目的评价1.00%派立明(AZOPT)与0.25%贝特舒点眼液每日两次点眼对原发性开角型青光眼、高眼压症及抗青光眼术后高眼压的降眼压效果及安全性。方法31例患者51只眼纳入为期2个月的前瞻性研究。在停用其他抗青光眼药物足够长的时间后测量基础值,用药后每2周复查一次共4次,同时观察眼局部及全身副作用。结果用药前眼压为23.85±1.80 mmHg,4次随访眼压下降均值6.55 mmHg(6.06～7.04),眼压下降率27.50%(26.62～28.59%)。少数病例出现烧灼感、视物模糊、口苦等症状,均为轻度能耐受,对视力、眼底无影响。结论派立明与贝特舒联合用药具有稳定的降眼压效果,具良好耐受性。     

Synthesis of [3H] vardenafil,Levitra®, using a new labeling technique

Tritium was introduced into the new orally active, selective phosphodiesterase type V (PDE V) inhibitor vardenafil (Levitra^®), by reduction of a suitable amide precursor with freshly prepared lithium aluminum tritide. A specific activity of 52.7 Ci/mmol (1.95 TBq/mmol) was achieved. In order to overcome the usual technical difficulties during the preparation of complex tritides a new and easy labeling technique which has considerable potential for various tritia‐tion procedures, was developed. Copyright © 2003 John Wiley & Sons, Ltd.     

Improvement in Wound Healing by Epidermal Growth Factor (EGF) Ointment. I. Effect of Nafamostat,Gabexate, or Gelatin on Stabilization and Efficacy of EGF

The healing effect of human epidermal growth factor (hEGF) on open wounds was studied in rats. No improvement in wound healing was found by topical application of EGF alone to open wound sites. We found an ointment containing EGF and a protease inhibitor, nafamostat mesilate or gabexate mesilate, or gelatin accelerated the healing rate of open wounds. Significant increases in the dry weight of the wound site granulation tissue, uronic acid (as an index of acid mucopolysaccharide) and hydroxyproline (as an index of collagen) were observed by treatment with EGF ointment containing nafamostat compared with the controls. The effects of the protease inhibitor on wound healing were dose dependent. Nafamostat was more efficient than gabexate or gelatin on wound healing. The degradation of ¹²⁵I-EGF in wound tissue homogenate was significantly decreased in the presence of a protease inhibitor, such as nafamostat or gabexate, or gelatin. These findings indicate that the stabilization of EGF at the wound site is an important factor in permitting the expression of its healing effects and suggest that the ointment containing EGF and a stabilizing agent would be a suitable dosage form for acceleration of wound repair.     

Characterization of Latent Transforming Growth Factor-β From Human Seminal Plasma

PROBLEM : Human seminal plasma is known to exhibit immunosuppressive activity. Transforming growth factor β (TGF-β) has been identified as an immunosuppressive factor in human seminal plasma. Biologically active TGF-β represents a family of 25-kDa homodimeric proteins linked with disulfide bonds. TGF-β associates with high molecular weight proteins noncovalently to form a type of latency that is biologically inactive. Quantitative distribution of active form of TGF-β versus inactive latent form of TGF-β, and mechanism of the TGF-β activation in human seminal plasma remain to be elucidated. PURPOSE : To characterize seminal plasma latent form of TGF-β, including its concentration, and the mechanism underlying the activation of TGF-β. METHOD : Gel filtrations on ACA-34 and Biogel P-60 were used to fractionate seminal plasma. TGF-β was measured by enzyme immunoassay using antibodies specific for TGF-β₁ and TGF-β₂, respectively. Radioreceptor assay with recombinant human [¹²⁵I]-TGF-β₁ was applied to qualitatively identify TGF-β₁. Kinetic experiments with various pH, temperature and time, along with protease inhibitors, were performed to delineate the activation mechanism of latent TGF-β. RESULTS : Human seminal plasma contained both TGF-β₁ and TGF-β₂, predominantly in latent form. The total concentration of TGF-β₁ averaged 238 ng/ml versus an average of 18 ng/ml for TGF-β₂. The in vitro activation or release of TGF-β₁, from latent TGF-β₁ was achieved only at acidic pH of <4.0, and was time and temperature dependent. At pH 3.7 and 37°C, a significant activation of latent TGF-β₁ was achieved after an incubation of only 15 min, reached the maximum at 120 min, and the activated TGF-β₁ remained relatively stable for at least 24 h. The activation was not inhibitable by a series of protease inhibitors examined, alone or in combination (e.g., phenylmethylsulfonyl fluoride, E-64, pepstatin, leupeptin, ethylenediamine tetraacetic acid). Competitive radioreceptor assay established the functional identity of TGF-β₁ in human seminal plasma with recombinant human TGF-β₁. CONCLUSION : Human seminal plasma TGF-β is biologically activated from high molecular weight latent TGF-β by acid pH. The acidic environment of female lower genital tract could represent an in vivo physiological condition for activation of seminal plasma TGF-β that may immunologically protect the integrity of sperm.     

Changes in the ratio of urinary α1-microglobulin to ulinastatin levels in patients with Alzheimer-type dementia and vascular dementia

Abstract Relationships between urinary levels of α1-microglobulin (α1M) and ulinastatin (UT) in patients with dementia were investigated. There were no significant differences in α1M and UT levels and α1M: UT ratios among three groups: age-matched control subjects, patients with either Alzheimer-type senile dementia (ATD) or vascular dementia (VD). Although a positive correlation was established between α1M and UT levels in these groups, the regression of the demented patients differed significantly from that of controls ( P <0.05). A tendency towards a negative correlation between α1M: UT ratios and the levels of severity or duration of the disease was displayed in the ATD group, whereas a tendency toward a positive correlation between α1M: UT ratios and the levels of severity was observed in the VD group. These results suggest that changes in the relationships between urinary levels of α1M and UT may provide a useful biochemical index for diagnoses of ATD and VD.     

Dose-response differences in the ability of ramipril to improve retention in diabetic mice

Ramipril blocks the conversion of angiotensin I to II. The literature indicates that diabetes is often associated with mild impairment of learning and memory. The study reports the effects of ramipril on memory retention in diabetic and non-diabetic mice. Mice were made diabetic by an injection of streptozocin. After overt signs of diabetes were present, diabetic or vehicle-treated mice were partially trained on a footshock active avoidance task. Immediately after training, ramipril (0.5–1.5 mg/kg s.c.) was administered and retention was tested by continuing training one week later until mice avoided footshock on five out of six trails. The results indicate that ramipril enhanced retention of both diabetic and control mice but it required about 5 times as much ramipril in diabetic as control mice to achieve the same effect on retention. Increased sensitivity to angiotensin II may play a role in cognitive impairment in diabetes.     

夹竹桃甙对Na~+、K~+-ATP酶抑制的动力学研究

本文对夹竹桃甙抑制Na~+、K~+-ATP酶的动力学作了探讨,并与乌本甙的作用进行了比较。结果表明:夹竹桃甙抑制Na~+、K~+-ATP酶,在Na~+、K~+浓度改变对均为非竞争性抑制,Na~+/K~+比例6:1时,为混合性抑制,而ATP对夹竹桃甙的作用几无影响。     

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。