Drugs affecting coagulation

The clotting cascade is a complex process and is an important survival mechanism. Major haemorrhage and thromboembolic events remain major causes of increased morbidity and mortality. Drugs affecting coagulation have primarily been utilized to treat or reduce the risk of thromboembolic events. However, the recent progress in the management of major trauma and treating coagulopathy has resulted in further research and development of drugs that improve clotting function. Knowledge of drugs used for both clinical circumstances is now required when working in anaesthesia or intensive care.     

Enzyme activities associated with the demyelinating phase of canine distemper

Summary Canine distemper, a naturally occurring viral disease of dogs which often terminates in parainfectious demyelination, was used as a model to study the role of acid proteinase, neutral proteinase and beta-glucuronidase in demyelination. These enzymes were higher in cerebella of dogs with distemper-associated demyelination than in age-matched controls. The highest elevations corresponded with the most severely demyelinated cerebella. The source of the increased enzymes activities was apparently unrelated to the lymphocytes present in areas of demyelination.The direct effect of distemper virus and serum on these enzymes was tested in canine glial monolayers. Virus infection resulted in lower enzyme activities in cells concomitant with the appearance of cellular lesions. There was a relative increase of beta glucuronidase activity in the media suggesting that distemper virus released pre-formed lysosomal enzymes. Serum which was obtained from dogs with distemper-associated demyelination and had previously demyelinated cerebellar explants, also decreased activities of all 3 enzymesin vitro.The 3 enzymes were measured in gerbil brains at various time intervals following unilateral cerebral infarction to determine if processes other than demyelination also caused these enzymes to be increased. Uncomplicated ischemic necrosis (24 h post infarction) did not alter the activities of these enzymes. Invasion of macrophages to ingest and digest necrotic tissue 10 days after infarction resulted in greatly increased acid proteinase and beta-glucuronidase, but unchanged neutral proteinase, activities.It was concluded that the increased activities of acid proteinase and beta-glucuronidase in demyelinated tissue probably are derived from macrophages ingesting damaged tissue. Neutral proteinase may be more specifically involved in the demyelinating process since this is partially located within myelin and can degrade the basic protein of myelin.Supported in part by Research grant Nos. GM 1052 and Al-09022 from National Institutes of Health Service, U.S. Public Health Service.     

反义核酸对肿瘤细胞多药抗性的抑制：作用靶点及作用方？…

为了用反义寡聚ＤＮＡ调控要霉素肿瘤细胞ＫＢ－Ａ－１的多药抗性,对反义核酸的预作用位点、作用方式和硫代化类似物进行了研究。筛选得到两段对应于翻译起始区（３）和Ｐ－糖蛋白ＡＴＰ结合位点（９）的２０聚反义片段,发现反义核酸的使用次数对结果的检测有很大影响,采用５μｍｏｌ／Ｌ５μｍｏｌ／Ｌ的反义片段９连续处理４ｄ,实现了将近５０％抑制效果,而其正义和错义链在１０μｍｏｌ／Ｌ沈度的同样处理条件下则没有检测到     

The Effect of different interventional treatment on P-Glycoprotein in different histopathological types and grades of primary hepatocellular carcinoma

Primary hepatocellular carcinoma( PHC) isvery common in China and chemotherapy has beenone of the classic and important methods for treatingPHC. Transcatheter arterial chemoembolization( TACE) has been one of main non- surgicaltherapiesfor PHC. The intrinsic or acquired multidrug resis-tance( MDR) has been an important problem inchemotherapy for PHC,because MDR tend to resultin cancer cells of PHC either failing to respond tochemotherapy or relapsing quickly after remission.Some stud…     

结肠癌P糖蛋白和p53蛋白表达的关系

目的 探讨Ｐ糖蛋白（Ｐ－ｇｐ０和Ｐ５３蛋白在结肠腺癌中的表达意义。方法 应用免疫组织化学方法检测术前进行化疗的１４０例结肠癌组织中的多药耐药基因产物Ｐ－ｇｐ和Ｐ５３蛋白的表达。结果 Ｐ－ｇｐ和Ｐ５３在结肠癌中的表达为２３．５７％（３３／１４０）和４０％（５６／１４０）。Ｐ－ｇｐ表达与结肠癌的组织学类型,浸润深度和淋巴结转移状况无关（Ｐ〉０．０５）,而Ｐ５３除与淋巴结转移状况有关外（Ｐ〈０．０５）,     

脑梗死患者急性期血小板膜糖蛋白表达的研究

目的　探讨脑硬死患者急性期血小板膜P -选择素 (CD6 2p)的表达及其与临床神经功能缺损程度的关系。方法　用流式细胞术测定 41例急性期脑梗死患者血小板膜CD6 2 p的表达。 结果　轻、中、重型脑梗死患者CD6 2 p的表达分别为 (1.38± 0 .2 9) %、(3.15± 1.5 8) %、(10 .46± 5 .0 7) % ,与正常对照组 (1.5 6± 0 .17) %比 ,轻型脑梗死患者CD6 2p的表达无显著性差异 (P >0 .0 5 ) ,中、重型脑梗死患者CD6 2 p的表达显著升高 (P <0 .0 5和0 .0 1)。结论　脑梗死患者急性期血小板膜CD6 2 p的表达与临床神经功能缺损程度有关。     

Autosomal recessive hypermyelinating neuropathy

We studied three patients from two kinships, affected by early onset hereditary motor and sensory neuropathy with probable autosomal recessive inheritance (HMSN type III). Morphological studies of sural nerve biopsies revealed an abnormal myelin proliferation. Two adult patients with long-term follow up, lost ability to walk at 28 and 22 years and showed severe involvement of the cranial nerves. Our observations suggest that hypermyelination neuropathy with early onset is a progressive disease with poor long-term prognosis. In one kinship the occurrence of the disease in two sibs of both sexes but not in parents, is consistent with an autosomal recessive inheritance. Familial cases of hypermyelination neuropathy have not been described in previous reports. Morphological aspects of this condition are compared with other forms of hypermyelination neuropathy.Supported by Telethon-Italy for the project: Chronic inflammatory polyradiculoneuropathy: electrophysiological and immunopathological studies     

A Simple and Rapid Fluorometric Determination Method of α1-Acid Glycoprotein in Serum Using Quinaldine Red

We examined different fluorescent probes suitable for fluorometric determination of ₁-acid glycoprotein (AGP) in serum. Quinaldine red (QR) was shown to bind strongly and selectively to AGP. Taking advantage of the enhanced fluorescence of QR in the presence of AGP, we developed a direct method for the determination of serum AGP without removal of other serum proteins such as albumin. AGP concentrations in serum of healthy volunteers and patients correlated well with results from the conventional single radial immunodiffusion (SRID) method (r = 0.93, slope = 1). The newly developed method is faster and has a larger analytical concentration range than the SRID method. This method can also be used to determine AGP in serum of experimental animals, and it can serve to monitor AGP serum concentrations for pharmacokinetic evaluation of basic drugs.     

Effect of platelet-activating factor on secretion of mucous glycoprotein from chinchilla middle ear epithelial cells in vitro

Platelet-activating factor (PAF) is a naturally occurring phospholipid that acts as a pleiotropic mediator and mediates cell-cell reactions under physiological and pathological conditions. Recently, it has been shown that PAF is a strong secretagogue of mucous glycoprotein in the airways, suggesting its role in mucous glycoprotein secretion and the pathogenesis of otitis media with effusion. In the current study, we examined the effect of PAF on mucous glycoprotein secretion in cultured chinchilla middle ear epithelial cells. PAF at 1 M significantly stimulated mucous glycoprotein secretion from cultured chinchilla middle ear epithelial cells. This action was concentration-dependent, with secretions reaching near maximum when the cells were incubated with PAF at 100 M. In a time-dependent study, PAF demonstrated an initial rapid stimulation of mucous glycoprotein secretion, followed by a gradual increase thereafter. A six-fold increase was seen in the first 2 h compared with controls. Cycloheximide, a protein synthesis inhibitor, demonstrated an inhibitory effect on PAF-stimulated mucous glycoprotein secretion in this study. These findings suggest that PAF plays an important role in the pathogenesis of otitis media with effusion by stimulating mucous glycoprotein secretion in vitro.Supported by NIH grant P0I-D000133 from the National Institute on Deafness and Other Communication Disorders.