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.     

Changes in the Eeg Background Activity of Children with Acute Lymphoblastic Leukemia During Cytotoxic Therapy

Thirteen children with acute lymphoblastic leukemia (ALL) were investigated before and during cytotoxic therapy. EEG findings were correlated with the clinical course and the therapy protocol and compared with normal data obtained from 295 healthy children. Frequency analysis of the background activity of the EEG revealed an initial slowing of the background activity prior to therapy and further slowing each time a combination of vincristine (VCR), daunorubicine (DAU) or adriblastine (ADR), prednisone (FRED), and L-asparaginase (L-ASP) was administered. The slowing of the background activity correlated only with the administration of these drugs. DAU, ADR, and FRED are not known to influence the EEG; therefore, VCR and L-ASP remain the primary candidates responsible for the central nervous system alteration.     

婴幼儿癫痫的外科治疗

目的探讨婴幼儿癫痫外科的手术意义。方法从2002-2005年有12例婴幼儿因海绵状血管瘤(4例)、发育不良神经上皮肿瘤(DNTs)(2例)、Sturge.weber综合征(1例)、半侧巨脑病(2例)、外伤后脑膜脑疤痕(1例)、脑脓肿疤痕组织(1例)、脉络丛乳头瘤(1例);由分别位于额(2例)、颞(4例)、顶(2例)、枕(2例)与额顶及颞顶(各1例)病变所致均为灾难性癫痫。当年龄在9—32(平均21.5)个月龄时做了病变及致痫灶切除/功能性大脑半球切除。癫痫开始于出生后5～20 (平均11.8)个月,每天或每周发作多次,抗痫药物治疗无效。患儿做手术评估是6—22(平均12.8)个月。3例患儿有偏瘫,7例显示有缓慢发展的认知功能减低表现。MRI、PET及V-EEG都证实了病灶及致痛灶。结果手术后无死亡及新的神经症状缺失。8例解除了癫痫(EngelⅠ级);2例罕有发作(EngelⅡ级);2例有值得的(worthwhile)改善(EngelⅢ级),7例认知功能也有改善,3例偏瘫者2例有改善。结论灾难性癫痫婴幼儿仔细选择手术病例,外科可以减轻、解除癫痫的疾苦。     

用Alabama分析法比较安氏Ⅰ类错中国人与美国白人颅颌面结构差异

目的:研究中国安氏Ⅰ类错成人与美国安氏Ⅰ类错白人牙颌颅面形态结构的差异。方法:从西安市11所大学2098名新生中选取符合标准的101名(男53名、女48名)安氏Ⅰ类错样本。拍摄头颅定位X线片,用第四军医大学口腔医学院头影测量软件测量,用Alabama分析法与美国安氏Ⅰ类错白人颅颌面测量结果进行比较分析。结果:中国西安地区安氏Ⅰ类错成人上下颌突度大,面型较突;平面倾斜度、上下中切牙倾斜度及下中切牙至NB线距均较大;Y轴相对SN平面夹角增大,生长方向为后下。结论:与美国安氏Ⅰ类错白人比较,中国西安地区安氏Ⅰ类错成人颅面结构呈现颌骨突度大、下切牙唇倾及下颌趋向后下等特征。     

活体顺序性荧光标记技术在实验性骨折愈合研究中的应用

目的介绍实验性骨折愈合研究中活体顺序性荧光标记的技术与方法。方法以成年兔胫骨骨折外固定为模型，术后分别以Tetracydin(TC，黄色，25mg／kg)、Calcein(CG，绿色，10mg／kg)、Xylenal(XO，桔色，90mg／kg)、Alizarin—complen(AE，红色，30mg／kg)四种荧光染料于兔颈部皮下定期注射；并于术后第3、6、12及24周活杀动物，解剖出胫骨，梯度乙醇脱水、脱脂，甲基丙烯酸甲脂包埋，切片厚度40～100μm，打磨，荧光显微镜下观察、摄像；同时通过组织学观察、X线摄片了解骨愈合速度与质量。结果顺序性荧光标记显示，加压组中钙化的内、外骨痴均于术后第2周出现于截骨处的远、近断端，但尚未形成骨性连接。亦无骨皮质的改建。外骨痴增生停止于术后12周，且骨皮质的改建至12周已渐减少．至术后24周已基本完成；对照组：内骨痴于术后第3周出现于截骨处远、近断端，无钙化的外骨痴形成，亦无骨皮质的改建；外骨痂增生停止于术后12周，骨皮质改建至24周尚未完成，其结果与组织学观察、X线摄片具有一致性。结论活体顺序性荧光标记技术可以从细胞水平判断新骨的开始时间、骨生长速度及生长方向，并能节约实验动物数量，是实验性骨折愈合研究中较为理想的研究手段。