小鼠眼球中脂肪酸组成分析

用气相色谱法分析了小鼠眼球中脂肪酸的组成及百分含量。分离是在２５ｍ×０．２５ｍｍＰＥＧ－２０Ｍ熔融石英毛细管柱内进行，眼球中１２种主要饱和及不饱和脂肪酸得到了定性和定量。本实验可为有关眼疾病的治疗、预防及生化方面的深入研究提供有意义的信息。     

Influence of hydrophobicity on the ion exchange selectivity coefficients for aromatic amines

Hydrophobic effects could play an important role in determining the selectivity of organic ions for ion-exchange resins in aqueous solutions. We used the octanol-water partition coefficient (P) and the chromatographic capacity factor (K') as indices of hydrophobicity of a series of primary and secondary amines, and examined their relationships with the amine selectivity coefficient (K) in binding to the Amberlite IRP-69 ion-exchange resin. Good correlations were found between log K versus log P and log K versus log K', but the relationship appears to be dependent on the degree of substitution at the amino nitrogen. These relationships may be useful for the estimation of selectivity coefficients of various amine drug candidates when they are considered for incorporation with ion-exchange resins in potential controlled-release systems.     

C-terminal modifications of nonpeptide renin inhibitors: improved oral bioavailability via modification of physicochemical properties.

We describe the development of a series of soluble, potent, and bioavailable nonpeptide renin inhibitors. These inhibitors derived from a series of novel nonpeptide renin inhibitors which were recently identified in our laboratories, by alteration of the nature of the C-terminus (P2') of the molecules. Introduction of basic substituents into modified hydroxyethylene dipeptide isosteres gave inhibitors with improved solubility as well as improved potency against human plasma renin. In addition, these modifications produced inhibitors which displayed markedly improved intraduodenal bioavailability in both the ferret and cynomolgus monkey. We also present data which demonstrate excellent efficacy in the monkey for A-74273 (65), with an intraduodenal bioavailability of 16 +/- 4% in the monkey, compared to 1.7 +/- 0.5% for the dipeptide renin inhibitor enalkiren (A-64662, 75). A-74273 is an example of a nonpeptide inhibitor which possesses a good balance of the desirable properties of potency, solubility, and lipophilicity and which is well absorbed into the intestine.     

The effect of bile duct ligation and bile diversion on FK506 pharmacokinetics in dogs.

Mongrel or beagle dogs were submitted to bile duct ligation, or to extraenteric biliary diversion by means of choledochoureterostomy. The kinetics of intravenously administered FK506 was not changed from control status two weeks after bile duct ligation, but the bioavailability of orally administered FK506 was nearly quadrupled. Following oral administration, the absorption of FK506 was highly variable. The results indicate that in dogs FK506 is absorbed from the intestine just as efficiently in the absence of enteric bile and in presence of exogenous bile salt supplement when compared with its absorption in presence of normal bile drainage. These findings with FK506 are different from those with cyclosporine after biliary obstruction or diversion and will have important practical as well as experimental ramifications.     

Preparation and identification of monoclonal antibodies against Penicillium marneffei]

OBJECTIVE: To prepare and identify monoclonal antibodies (mAbs) against Penicillium marneffei. METHODS: Recombinant mannoprotein1 (MP1) of Penicillium marneffei was used to immunize BALB/c mice, and anti-MP1 mAbs were obtained by means of hybridoma. Screening and identification of the mAbs were subsequently performed with indirect enzyme-linked immunosorbent assay and Western blotting, respectively. RESULTS: Four hybridomas producing antibodies against Penicillium marneffei were obtained, and the IgG isotypes of the 4 mAbs were identified as IgG1 with affinity constants (K) of 8.2x10(-9), 4.7x10(-9), 6.5x10(-9) and 2.7x10(-9), respectively. Western blotting demonstrated specific recognition of Aspergillus fumigatus MP1 by the obtained mAbs. CONCLUSION: The 4 hybridomas producing anti-MP1 mAbs with high specificity and affinity can be of significant value in the diagnosis of Penicilliosis marneffei infections.     

术前无创正压通气治疗对脊柱侧凸患者围手术期肺功能的影响

目的:研究术前使用呼吸机无创正压通气治疗对脊柱侧凸患者围手术期肺功能的影响。方法:将40例Cobb角≥60°、肺功能存在中度以上限制性通气功能障碍、行脊柱侧凸矫形术的脊柱侧凸患者,随机分成A组和B组,每组20例。A组在术前采用BiPAP呼吸机,经用面罩无创正压通气(NIPPV)治疗1个月;B组常规术前准备。观察A组患者治疗前后肺功能的改善及两组患者围手术期肺功能的差异。结果:两组患者性别、年龄、身高、体重、Cobb角度、手术时间、手术径路、融合椎体数等基本情况比较无统计学差异(P>0.05);A组患者经NIPPV治疗后肺活量(VC)、肺活量占预计值的百分比(VC%)、用力肺活量(FVC)、第一秒最大呼气量(FEV1.0)、最大通气量(MVV)和最大通气量占预计值的百分比(MVV%)较治疗前明显改善(P<0.01);两组患者术中氧合指数、术后拔管时间、拔管后15min动脉血气PO2、PCO2比较有显著性差异(P<0.05)。结论:术前无创正压通气治疗可改善脊柱侧凸患者围手术期的肺功能,可缩短手术后气管插管的拔管时间,改善术后通气功能,有助于脊柱侧凸患者手术后早期恢复。     

舒芬太尼用于全凭静脉麻醉40例研究

目的：探讨舒芬太尼全凭静脉复合麻醉时对听觉诱发电位指数、血流动力学和术后复苏的影响.方法：40例美国标准协会（ASA）Ⅰ～Ⅱ级病人择期行胆囊切除手术,随机分为Ⅰ组（舒芬太尼组）和Ⅱ组（芬太尼组）,记录两组病人麻醉期间各时间点的听觉诱发电位指数（AEPI）值、收缩压、舒张压、心率和SpO2.结果：Ⅱ组插管后1 min、2 min的收缩压较Ⅰ组升高,而插管后1 min的心率较Ⅰ组降低（P＜0.05）;Ⅰ组插管后1 min、2 min和3 min时的AEPI值低于Ⅱ组（P＜0.05）;Ⅰ组拔管后至定向力恢复的时间较Ⅱ组长（P＜0.05）;Ⅰ组丙泊酚的用量较Ⅱ组少（P＜0.05）.结论：等效剂量的舒芬太尼较芬太尼的全凭静脉复合麻醉可以使病人达到更为合适的麻醉深度,并能使血流动力学更加稳定,同时可减少丙泊酚用量.     

Mycophenolate Mofetil Is Associated with Altered Expression of Chronic Renal Transplant Histology

Mycophenolate mofetil (MMF) reduces acute rejection in controlled trials of kidney transplantation and is associated with better registry graft survival. Recent experimental studies have demonstrated additional antifibrotic properties of MMF, however, human histological data are lacking. We evaluated sequential prospective protocol kidney biopsies from two historical cohorts treated with cyclosporine (CSA)-based triple therapy including prednisolone and either MMF (n = 25) or azathioprine (AZA, n = 25). Biopsies (n = 360) were taken from euglycemic kidney-pancreas transplant recipients. Histology was independently assessed by the Banff schema and electron microscopic morphometry. MMF reduced acute rejection and OKT3 use (p < 0.05) compared with AZA. MMF therapy was associated with limited chronic interstitial fibrosis, striped fibrosis and periglomerular fibrosis (p < 0.05-0.001), mesangial matrix accumulation (p < 0.01), chronic glomerulopathy scores (p < 0.05) and glomerulosclerosis (p < 0.05). MMF was associated with delayed expression of CSA nephrotoxicity, reduced arteriolar hyalinosis, striped fibrosis and tubular microcalcification (p < 0.05-0.001). The beneficial effects of MMF remained in recipients without acute rejection. Retrospective analysis shows that MMF therapy was associated with substantially reduced fibrosis in the glomerular, microvascular and interstitial compartments, and a delayed expression of CSA nephrotoxicity. These outcomes may be due to a limitation of immune-mediated injury and suggest a direct effect of reduced fibrogenesis.