Formulation and in Vitro-in Vivo Evaluation of Sustained-Release Lithium Carbonate Tablets

The release of lithium carbonate incorporated into polymethylmethacrylate, poly vinyl chloride, hy-drogenated vegetable oil, and carbomer matrix tablets was studied in vitro. The formulation containing 10% carbomer showed a sustained-release profile comparable to that of a standard, commercially available, sustained-release preparation containing 400 mg lithium carbonate embedded in a composite material. In vivo the newly formulated and standard sustained-release lithium carbonate tablets were compared to an oral solution and conventional lithium carbonate tablets in 12 healthy subjects. These crossover studies showed that the sustained-release tablets produced a flatter serum concentration curve than the oral solution and conventional tablet, without loss of total bioavailability.     

浅谈电子文档的原始性和真实性及法律证据作用

该文针对电子文件或档案的原始性真实性与电子档案的法律证据作用,参考了最新的研究结果,并提出了自己的思考,逐步探讨了它们的涵义及关系.     

肝癌组织中HOXA9 mRNA的表达及其临床意义

目的研究肝癌病例癌组织、癌旁组织及非癌肝组织中HOXA9 mRNA的表达及其临床意义.方法标本经10%中性福尔马林固定后常规制作石蜡包埋切片,HOXA9 mRNA行原位杂交检测.结果临床分析发现术后血清AFP值、AFU值、Glo值、PAB值及SHCSP阳性率均有明显减少.癌组织HOXA9mRNA阳性表达评分(1.94±1.69)明显低于非癌肝组织(3.17±1.70),两者有显著差异;癌旁组织HOXA9mRNA阳性表达评分(2.54±1.20)与非癌肝组织及癌组织无显著差异.癌组织、癌旁组织及非癌肝组织三者HOXA9mRNA阳性表达率(54.84%、76.92%、83.33%)无显著差异.除HCC中HOXA9RNA阳性表达评分(1.81±1.78)显著低于MHC(2.75±0.50)外,HOXA9mRNA表达阳性率及阳性评分与癌分化程度、AFP值、SHCSP是否阳性、AFU值、肝硬化有无、转移情况、有无癌栓、大体形态及肿块最大径等临床病理特征均无明显关系.结论本研究结果显示HOXA9mRNA可能与肝癌的发生有密切关系.临床上检测HOXA9mRNA的表达情况对肝癌的早期发现和早期诊断可能有较重要的临床意义,值得深入研究.     

Highly resolved in vivo 1H NMR spectroscopy of the mouse brain at 9.4 T.

An efficient shim system and an optimized localization sequence were used to measure in vivo 1H NMR spectra from cerebral cortex, hippocampus, striatum, and cerebellum of C57BL/6 mice at 9.4 T. The combination of automatic first- and second-order shimming (FASTMAP) with strong custom-designed second-order shim coils (shim strength up to 0.04 mT/cm2) was crucial to achieve high spectral resolution (water line width of 11-14 Hz). Requirements for second-order shim strengths to compensate field inhomogeneities in the mouse brain at 9.4 T were assessed. The achieved spectral quality (resolution, S/N, water suppression, localization performance) allowed reliable quantification of 16 brain metabolites (LCModel analysis) from 5-10-microL brain volumes. Significant regional differences (up to 2-fold, P < 0.05) were found for all quantified metabolites but Asp, Glc, and Gln. In contrast, 1H NMR spectra measured from the striatum of C57BL/6, CBA, and CBA/BL6 mice revealed only small (<13%, P < 0.05) interstrain differences in Gln, Glu, Ins, Lac, NAAG, and PE. It is concluded that 1H NMR spectroscopy at 9.4 T can provide precise biochemical information from distinct regions of the mouse brain noninvasively that can be used for monitoring of disease progression and treatment as well as phenotyping in transgenic mice models.     

还原型谷胱甘肽和L-NAME对体外培养的脊髓运动神经元的影响

目的 :探讨还原型谷胱甘肽 (GSH)和L NAME对体外培养的脊髓运动神经元的保护作用。方法 :不同浓度的GSH和L NAME作用于脊髓运动神经元 ,3d后计算存活率。并测量存活率高的两组和对照组的免疫细胞化学标本的神经元形态学指标。结果 :GSH 10mmol·L-1和L NAME 1× 10 -3 mol·L-1组存活率最高。两实验组轴突长度、树突总长度、树突分叉点数目和胞体面积高于对照组。结论 :抗氧化剂和NOS抑制剂可以提高脊髓运动神经元的存活率 ,促进神经元生长     

Influence of different preservation solutions and intentional hemodilution of recipient on viability of preserved and transplanted rat kidneys

Abstract. A total of 81 rat kidney grafts, flushed out and cold stored in either Sacks' or University of Wisconsin (UW) solution, were transplanted into hemodiluted (Hct = 30%± 4%) or untreated (Hct = 43%± 3%) recipients. The cold ischemia times (CIT) used were 24 and 36 h. One week after transplantation, the surviving recipients ( n = 67) were contralaterally nephrectomized. The experiment was terminated after a total period of 4 weeks, and the percentage of surviving animals was determined for each treatment. Data was pooled and the results show that grafts cold stored in UW solution were viable to a significantly greater extent and after longer CIT than grafts cold stored in Sacks' solution (47% vs 23%; P < 0. 05). Recipient hemodilution did not improve graft viability (39% vs 32%; NS). Kidneys cold stored for 24 h were viable to a greater extent than kidneys with a CIT of 36 h (50% vs 15%; P < 0. 01).     

Morphological and biochemical correlates of chemical induced injury in the lung

We have reviewed some of the factors which contribute to lung damage by various toxicants. These include disposition of the chemical, its metabolism, individual cell type susceptibility and the potential for the tissue to repair. We have discussed the use of biochemical parameters to measure the functional activity of individual cell types in order to predict the damage to specific cell types and concluded that careful morphological analysis of lung tissue is likely to provide a more sensitive and informative measure of specific cell type injury. However, in order to investigate the mechanism of toxicity of pulmonary toxicants it is essential to establish the primary biochemical event that leads to cell damage and morphological change. The importance of separating the relevant biochemical change(s) from the cascade of biochemical events associated with dead and dying cells and the reparative response of the lung is emphasised.This report results from a discussion sponsored and organised by the Advisory Subgroup in Toxicology (AST) of the European Science Foundation's Standing Committee for the European Medical Research Councils and held at the Medical Research Council Toxicology Unit, Carshalton, U. K. Those taking part were: W. N. Aldridge (AST; as above); J. Bignon (Unit for Research in Renal and Pulmonary Pathology, University of Paris, Creteil, France); P. H. Burri (Section of Developmental Biology, Institute of Anatomy, University of Berne, Switzerland); G. M. Cohen (as above); D. Dinsdale (MRC Toxicology Unit, Carshalton U. K.); P. Hedqvist (Dept. of Physiology, Karolinska Institute, Stockholm, Sweden); D. Henschler (AST; Dept. of Toxicology and Pharmacology, University of Wurzburg, FDR); G. J. Laurent (Biochemistry Unit, Cardiothoracic Institute, University of London, London, U. K.); R. Lauwerys (AST Industrial and Medical Toxicology Unit, University of Louvain, Brussels, Belgium); F. Lembeck (AST; Dept. for Experimental and Clinical Pharmacology, University of Graz, Austria); N. Lery (AST; Poison Control Centre, Lyon, France); P. Moldeus (Dept. of Forensic Medicine, Karolinska Institute, Stockholm, Sweden); B. Nemery (MRC Toxicology Unit, Carshalton, U. K.); A. Saria (Dept. for Experimental and Clinical Pharmacology, University of Graz, Austria); L. L. Smith (as above);B. Terracini (AST; Dept. of Pathology and Cancer Epidemiology, University of Turin, Italy)     

Familial Mitochondrial Encephalomyopathy with Stroke-like Episodes and Episodic Disturbances of Consciousness: A Study of Pedigree Including Three Generations with Multisystemic Abnormalities

Abstract: We report here two cases in a family with pleomorphic clinical features which include mitochondrial myopathy, encephalopathy, stroke-like episodes, episodic disturbances of consciousness and other multisystemic abnormalities. The other signs observed in multisystemic abnormalities were ophthalmoplegia, short stature, diabetes mellitus, diabetes insipidus, renal dysfunction, optic atrophy, retinal degeneration, impairment of hearing and mental retardation or deterioration. A symptomatological variation was observed in cases in the same family. It is suggested that these widely varying symptoms may be expressions caused by a common biochemical defect which involves different tissuesin different individuals in the family. The syndromes observed in the present cases were compared with other possibly-related mitochondrial encephalomyopathies.     

Zero-Order Release Formulation of Oxprenolol Hydrochloride with Swelling and Erosion Control

Zero-order release of oxprenolol hydrochloride was obtained by controlling the swelling and erosion of the matrix. This formulation involves only mixing of drug, hydroxypropylmethylcellulose (HPMC), and sodium carboxymethylcellulose (Na CMC) at the ratio of 1:0.4:1.6, respectively, and compressing the mixture directly into tablets. The in vitro release pattern from this optimized matrix tablet was reproducible. Accelerated stability studies revealed that the optimized formulation remains stable for an approximately 2-year shelf life. This sustained-release (SR) tablet was evaluated in dogs, and for comparison a conventional (CV) formulation was also given at the same dose level. Plasma oxprenolol levels were monitored by a sensitive and specific high-performance liquid chromatographic (HPLC) method. Significant differences in the pharmacokinetic parameters, i.e., lower C _max, higher values of t _max, MRT, AUC, and plasma concentration at 24 hr, and nearly constant plasma levels over 12 hr, indicated that the SR matrix tablet is superior to the CV rapid-releasing formulation. The in vitro release parameters and in vivo pharmacokinetics correlated well.