尼群地平固体分散体微丸稳定性的初步研究

目的考察尼群地平固体分散体微丸的稳定性。方法通过影响因素试验和加速试验,考察尼群地平固体分散体微丸的外观,药物和有关物质的含量,以及药物溶出速度（T80）的变化。结果该固体分散体微丸对温度和湿度稳定,对光不稳定,模拟上市包装后稳定性良好。结论尼群地平固体分散体微丸经包装后稳定性较好。     

Pharmacokinetics and pharmacodynamics of a sustained-release biodegradable pellet containing imidapril, a new angiotensin-converting enzyme inhibitor in spontaneously hypertensive rats

The pharmacokinetics and pharmacodynamics (PK/PD) of a sustained-release biodegradable pellet containing imidapril, a new angiotensin-converting enzyme (ACE) inhibitor, were investigated in comparison with those of an osmotic pump in male spontaneously hypertensive rats (SHRs). A pellet was prepared from copolymer of -lactic acid and glycolic acid by the melt-pressing technique. Imidapril was released in vitro from the pellet at an approximately zero-order rate and the release profile was similar to that of the osmotic pump. Imidapril was administered subcutaneously via a pellet or an osmotic pump implanted under the skin in the back of SHRs. Plasma concentrations of imidaprilat as an active metabolite of imidapril, plasma ACE activity and systolic blood pressure (SBP) were determined periodically. The plasma concentration of imidaprilat during the administration of a pellet was maintained for 4 weeks, and the plasma concentration profile was close to that of the osmotic pump. Both groups of pellet and osmotic pump significantly inhibited plasma ACE activity and reduced SBP for 4 weeks, and these action profiles were similar in both groups. In addition, in vivo release profile of the pellet was close to the in vitro release profile, and the in vivo release profiles of the pellet and the osmotic pump were similar to each other. From these results, it was found that the PK/PD of a biodegradable pellet were close to those of the osmotic pump, and it was shown that the pellet may be a useful system to maintain the plasma concentration of imidaprilat for a long time.     

Naloxone effects on schedule-controlled behavior in morphine-pelleted rats

The effects of morphine pellet implantation and naloxone administration were examined in rats lever pressing under inter-response time schedules of food presentation. Subcutaneous implantation of a morphine pellet initially decreased lever-pressing rates. Tolerance to this effect developed within 3–4 days. Naloxone (0.25–1.0 mg/kg) decreased response rates in morphine-pelleted rats in a dose-dependent and time-dependent manner. All doses of naloxone severely decreased rates of lever pressing on days four to nine post-pellet. This rate-decreasing effect persisted 7–17 days for 0.25 mg/kg naloxone, 9–22 days for 0.50 mg/kg, and 13–28 days for 1.0 mg/kg. Decreases in response rate were due to an increased frequency of long pauses and not to marked shifts in the temporal patterning of those lever presses that did occur. Changes in response rate after naloxone were accompanied by body weight loss. Area values summarizing the naloxone-induced changes in response rate or body weight over time after pellet implantation increased as a function of naloxone dose. Naloxone (0.25–1.0 mg/kg) did not alter performance by placebo-pelleted rats.     

小金丸加减抗肿瘤的实验研究

本实验用小金丸加减治疗S_(180)小鼠。主要观察指标有全血粘度和瘤重。结果显示:小金丸加减能明显降低S_(180)小鼠的全血粘度,显著抑制肿瘤生长,而对小鼠体重增长无明显抑制作用。提示小金丸加减具有良好的改善血瘀状态和抑制肿瘤生长的作用,且有副作用小的优点。这为血瘀是肿瘤的主要病机之一的理论提供了实验依据。     

Airgun Pellet Appendicitis

A rare case in which an airgun pellet was present in an inflamed appendix is reported. The significance of foreign bodies seen in the appendix on abdominal radiographs is discussed.     

Sister chromatid exchange in vivo in mice: I. The influence of increasing doses of bromodeoxyuridine

Bromodeoxyuridine (BrdUrd) pellets weighing either 20, 25, 30, 35, 40, 45, or 53 mg were implanted subcutaneously in strain DBA/2J male mice. Femoral bone marrow cells were analyzed for sister chromatid exchange (SCE) and chromosome aberration frequencies, mitotic indices, and cellular replication kinetics. Small but statistically significant BrdUrd dose-dependent increases of SCEs were observed, whereas chromosome aberrations were induced at low frequencies and occurred independently of BrdUrd dose. The mitotic index remained relatively constant for all doses. A slight inhibition of cellular replication, as manifested by a reduction in third division cells at the 40- and 45-mg doses, was observed. The use of an intense fluorescent light source in the fluorescence-plus-Giemsa technique provided consistently good sister chromatid differentiation at pellet doses substantially lower than those previously used by other investigators.     

Synergistic antiinflammatory effects of pinitol and glucosamine in rats

This study evaluated the antiinflammatory activities of pinitol and glucosamine either alone or in combination against carrageenan- and cotton pellet-induced acute and subacute inflammation in rats. Five groups were included in each of the acute and subacute inflammation studies: the vehicle control group, positive control group (aminopyrine 100 mg/kg), pinitol group (20 mg/kg), glucosamine group (25 mg/kg) and a pinitol (20 mg/kg) and glucosamine (25 mg/kg) combination group. When 20 mg/kg of pinitol was administered to the rats, paw edema induced by the carrageenan injection was significantly suppressed and the level of granuloma formation induced by the cotton pellet implantation was slightly reduced. When 25 mg/kg of glucosamine was administered, paw edema caused by the acute inflammation was slightly reduced and the level of granuloma formation caused by the subacute inflammation was strongly suppressed. Although the combined application of pinitol and glucosamine did not have an additional antiinflammatory effect on the paw edema caused by acute inflammation, it did have an increased antiinflammatory effect on the formation of granuloma induced by subacute inflammation. Therefore, pinitol and glucosamine have an antiinflammatory effect on acute and subacute conditions. Moreover, a synergistic antiinflammatory effect against subacute inflammation was observed when the two chemicals were administered in combination.     

Fluorine-19 or phosphorus-31 NMR spectroscopy: a suitable analytical technique for quantitative in vitro metabolic studies of fluorinated or phosphorylated drugs

Fluorine-19 or phosphorus-31 NMR (¹⁹F NMR or ³¹P NMR) spectroscopy provides a highly specific tool for identification of fluorine- or phosphorus-containing drugs and their metabolites in biological media as well as a suitable analytical technique for their absolute quantification. This article focuses on the application of in vitro ¹⁹F or ³¹P NMR to the quantitative metabolic studies of some fluoropyrimidine or oxazaphosphorine drugs in clinical use. The first part presents an overview of the advantages (non-destructive and non-selective direct quantitative study of the biological matrices) and limitations (expensive cost of the spectrometers, limited mass or concentration sensitivity) of NMR spectroscopy. The second part deals with the criteria to be considered for successful quantification by NMR (uniform excitation over the entire spectral width of the spectrum, resonance signals properly characterised by taking into account T₁ values and avoiding NOE enhancements, optimisation of the data processing, choice of a suitable standard reference). The third and fourth parts report some examples of quantification of 5-fluorouracil, its prodrug capecitabine, 5-fluorocytosine and their metabolites in bulk solutions (biofluids, tissue extracts, perfusates and culture media) and heterogeneous media (excised tissues and packed intact cells) as well as cyclophosphamide and ifosfamide in biofluids. These two parts emphasise the high potential of in vitro ¹⁹F or ³¹P NMR for absolute quantification, in a single run, of all the fluorine- or phosphorus-containing species in the matrices analysed. The limit of quantification in bulk solutions is 1–3 μM for ¹⁹F NMR and approximately 10 μM for ³¹P NMR. In heterogeneous media analysed with ¹⁹F NMR, it is 2–5 nmol in excised tissues and cell pellets.     

Anti-inflammatory activity of Justicia prostrata gamble in acute and sub-acute models of inflammation

In this study, the aqueous (AQJP) and alcoholic (ALJP) extracts of the whole plant of Justicia prostrata Gamble (Acanthaceae) were screened for their acute and subacute anti-inflammatory activities using carrageenan-induced acute inflammation and cotton-pellet-induced granuloma (subacute inflammation), respectively, in rats. In the carrageenan-induced rat paw oedema model, both extracts were found to exhibit maximum reduction in paw volume at the first hour in a dose-dependent manner. At the dose of 500 mg/kg p.o., both extracts AQJP and ALJP showed maximum inhibition (51.39% and 62.5%, respectively) in rat paw oedema volume at the first hour of carrageenan-induced acute inflammation. In the cotton pellet granuloma assay, AQJP and ALJP at the dose of 500 mg/kg p.o. suppressed the transudative, exudative and proliferative phases of chronic inflammation. These extracts were able to (i) reduce the lipid peroxide content of exudates and liver and (ii) normalize the increased activity of acid and alkaline phosphatases in serum and liver of cotton pellet granulomatous rats. Preliminary phytochemical screening revealed the presence of lignans, triterpenes and phenolic compounds in ALJP, whereas phenolic compounds and glycosides in AQJP. The anti-inflammatory properties of these extracts may possibly be due to the presence of phenolic compounds. The anti-inflammatory effects produced by the extracts at the dose of 500 mg/kg, p.o. was comparable with the reference drug diclofenac sodium (5 mg/kg p.o.).     

生长分化因子5诱导人骨髓间充质干细胞微团成软骨分化的研究

[目的]探讨应用生长分化因子5(growth differentiation factor 5,GDF-5)诱导人骨髓间充质干细胞(human bone marrow mesenchymal stem cells,hMSCs)微团成软骨分化的可行性及效果。[方法]体外分离培养hMSCs,取第3代细胞实验。将hMSCs分别用无血清H-DMEM和含10、20、50、100 ng/ml GDF-5的软骨诱导液(chondrogenic medium,CM)诱导,显微镜下观察细胞形态变化,MTT法检测各组细胞的增殖情况。诱导2周后重悬细胞,以5×106/ml的细胞密度离心构建微团,继续诱导2周。RT-PCR检测两组细胞Ⅱ型胶原mRNA的表达。免疫组化、甲苯胺蓝染色检测Ⅱ型胶原和蛋白多糖表达。[结果]hMSCs呈梭形、漩涡状生长。100 ng/ml GDF-5诱导的hMSCs呈圆形或多角形。五组微团分别由无血清H-DMEM、含10,20,50,100 ng/ml GDF-5的软骨诱导液诱导2周后,除H-DMEM组无Ⅱ型胶原mRNA、Ⅱ型胶原蛋白和蛋白多糖的表达外,其他各组Ⅱ型胶原mRNA、Ⅱ型胶原蛋白和蛋白多糖的表达呈...