Chronic Inhalation Toxicity and Carcinogenicity Testing of Respirable Fibrous Particles

On May 8–10, 1995, a workshop on chronic inhalation toxicity and carcinogenicity testing of respirable fibrous particles was held in Chapel Hill, North Carolina. The workshop was sponsored by the Office of Pollution Prevention and Toxics, U.S. Environmental Protection Agency (EPA), in collaboration with the National Institute of Environmental Health Sciences (NIEHS), the National Institute for Occupational Safety and Health (NIOSH), and the Occupational Safety and Health Administration (OSHA). The goal of the workshop was to obtain input from the scientific community on a number of issues related to fiber testing. Major issues for discussion were: (i) the optimal design and conduct of studies of the health effects of chronic inhalation exposure of animals to fibers; (ii) preliminary studies which would be useful guides in designing the chronic exposure study; (iii) mechanistic studies which would be important adjuncts to the chronic exposure study to enable better interpretation of study results and extrapolation of potential effects in exposed humans; and (iv) available screening tests which can be used to develop a minimum data set for (a) making decisions about the potential health hazard of the fibers and (b) prioritizing the need for further testing in a chronic inhalation study. After extensive discussion and debate of the workshop issues, the general consensus of the expert panel is that chronic inhalation studies of fibers in the rat are the most appropriate tests for predicting inhalation hazard and risk of fibers to humans. A number of guidances specific for the design and conduct of prechronic and chronic inhalation studies of fibers in rodents were recommended. For instance, it was recommended that along with other information (decrease in body weight, systemic toxicity, etc.), data should be obtained on lung burdens and bronchoalveolar lavage fluid analysis to assist in establishing the chronic exposure levels. Lung burden data are also important for quantifying aspects of risk assessment related to dosimetric adjustments before extrapolation. Although mechanistic studies are not recommended as part of the standard chronic inhalation studies, the expert panel stressed the need for obtaining mechanistic information as far as possible during the course of subchronic or chronic inhalation studies. At present, no single assay and battery of short-term assays can predict the outcome of a chronic inhalation bioassay with respect to carcinogenic effects. Meanwhile, several short-termin vitroandin vivostudies that may be useful to assess the relative potential of fibrous substances to cause lung toxicity/carcinogenicity have been identified.     

光照疗法对新生儿红细胞谷胱甘肽还原酶活性的影响

作者对光照疗法（光疗）前及光疗后于口服维生素Ｂ＿２（４３例）和不予口服维生素Ｂ＿２（１７例）的黄疸新生儿的红细胞谷胱甘肽还原酶（ＧＲ）的活性进行了动态观察。结果显示，接受短期光疗的黄疸新生儿其红细胞ＧＲ活性较光疗前的ＧＲ活性有显著下降，光疗后予口服维生素Ｂ＿２可使下降的红细胞ＧＲ活性回升，而不予补充维生素Ｂ＿２者的红细胞ＧＲ活性继续下降。光疗的时间越长，红细胞ＧＲ活性的下降越明显，补充维生素Ｂ＿２使红细胞ＧＲ活性回复到正常水平所需的时间也越长。短期光疗也可引起体内维生素Ｂ＿２的降解，导致红细胞ＧＲ活性的下降，为避免因红细胞ＧＲ活性下降引起的红细胞额外破坏，对接受光疗的黄疸新生儿常规补充维生素Ｂ＿２的是必要的。     

Lack of biliary excretion of Cd linked to an inherent defect of the canalicular isoform of multidrug resistance protein (cMrp) does not abnormally stimulate accumulation of Cd in the Eisai hyperbilirubinemic (EHB) rat liver

A new mutant, the Eisai hyperbilirubinemic (EHB) rat, shows no inherent expression of the canalicular isoform of the multidrug resistance protein (cMrp) in the liver. It has defective biliary secretion of organic anions such as bilirubin glucuronides, bromosulfophthalein (BSP), cysteinyl leukotrienes, glutathione (GSH) and bile acid sulfate and glucuronides. When rats were injected intravenously with CdCl₂, biliary excretion of Cd over 30 min was 0.28% and 0.004% of the total dose in Sprague-Dawley (SD) and EHB rats, respectively. Six SD rats and five EHB rats were fed a diet containing Cd. Bile Cd was detected at the level of 2 ng/20 min in SD rats, but not in EHB rats. There was no significant difference of hepatic Cd concentration between SD and EHB rats. Furthermore, there were no significant differences of renal and intestinal Cd, and hepatic and renal metallothionein (MT) concentrations between the SD and EHB groups. Biliary excretion of reduced-GSH for 20 min was 1.3 ± 0.3 mg and 3.6 ± 0.9 μg in SD and EHB rats, respectively. Our results suggest that hepatobiliary excretion of exogenous Cd is mediated mainly via carrier transport, including a cMrp or GSH carrier, but that the lack of the transport pathway does not contribute to abnormal accumulation of Cd in the liver. Received: 12 August 1996 / Accepted 7 November 1996     

The future of outcomes measurement: item banking,tailored short-forms,and computerized adaptive assessment

The use of item banks and computerized adaptive testing (CAT) begins with clear definitions of important outcomes, and references those definitions to specific questions gathered into large and well-studied pools, or “banks” of items. Items can be selected from the bank to form customized short scales, or can be administered in a sequence and length determined by a computer programmed for precision and clinical relevance. Although far from perfect, such item banks can form a common definition and understanding of human symptoms and functional problems such as fatigue, pain, depression, mobility, social function, sensory function, and many other health concepts that we can only measure by asking people directly. The support of the National Institutes of Health (NIH), as witnessed by its cooperative agreement with measurement experts through the NIH Roadmap Initiative known as PROMIS (www.nihpromis.org), is a big step in that direction. Our approach to item banking and CAT is practical; as focused on application as it is on science or theory. From a practical perspective, we frequently must decide whether to re-write and retest an item, add more items to fill gaps (often at the ceiling of the measure), re-test a bank after some modifications, or split up a bank into units that are more unidimensional, yet less clinically relevant or complete. These decisions are not easy, and yet they are rarely unforgiving. We encourage people to build practical tools that are capable of producing multiple short form measures and CAT administrations from common banks, and to further our understanding of these banks with various clinical populations and ages, so that with time the scores that emerge from these many activities begin to have not only a common metric and range, but a shared meaning and understanding across users. In this paper, we provide an overview of item banking and CAT, discuss our approach to item banking and its byproducts, describe testing options, discuss an example of CAT for fatigue, and discuss models for long term sustainability of an entity such as PROMIS. Some barriers to success include limitations in the methods themselves, controversies and disagreements across approaches, and end-user reluctance to move away from the familiar.     

大狼毒三萜类化学成分的研究

自大戟科(Euphorbiaceae)植物大狼毒(Euphorbia nematocypha Hand—Mazz)根的乙醇提取物的苯溶解部分,经20%AgNO₃硅胶层析,分离得到七个三萜类成分。根据光谱(IR,EIMS,¹H—NMR和¹³C—NMR)和化学方法,确定其中一个化合物为新化合物,命名为大狼毒醇(nematocyphol,Ⅳa),其它化合物为已知物:印度荆芥醇乙酸酯(nepehinol acetate Ⅰ),日尔曼醇乙酸酯(germanicol acetate Ⅱ),大戟醇(euphol,Ⅲ),蒲公英醇(taraxasterol,Ⅴa),24-亚甲基环阿尔廷醇(24-methylenecycloartanol,Ⅴa)和印度荆芥醇(nepehinol,Ⅶa)。这些化合物均为首次从大狼毒中得到。     

The interleukin-5 messenger RNA expression in a patient with idiopathic hypereosinophilic syndrome

Interleukin-5 has a specific role in various eosinophilic activities. It is the predominant cytokine produces by activated T-lymphocytes isolated from patients with idiopathic hypereosinophilic syndrome. We studied a young patient suffering from idiopathic hypereosinophilic syndrome who presented with Horner's syndrome, peripheral neuropathy and skin ulcers. The IL-5 gene expression by CD4⁺ T-lymphocytes and the peripheral eosinophil count were raised. The skin ulcers continued to deteriorate despite a swift reduction of the IL-5 gene expression and peripheral eosinophil count following systemic corticosteroid treatment. We suggest that peripheral eosinophilia may not be responsible for the damage in skin lesions and more aggressive treatment may be required.     

Neurotrophin-like immunoreactivity in the human pre-term newborn, infant, and adult cerebellum

The immunohistochemical occurrence of the neurotrophin (NT) proteins nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-4 (NT-4), and neurotrophin-3 (NT-3) is shown in the pre-term newborn, infant, and adult human post-mortem cerebellum. The NT-like immunoreactive structures were unevenly distributed and showed regional differences among cerebellar lobules and folia. NGF-, NT-4-, and NT-3-positive neuronal perikarya were observed in all specimens examined. At variance with the other neurotrophins, the BDNF antiserum labelled neuronal cell bodies only in newborn life and infancy, as well as extensive nerve fibre systems, whose density increased with age. The NT-antibodies, tested by Western blot on human cerebellum homogenates, revealed immunoreactive bands corresponding to proteins of heterogenous molecular weight. The results obtained provide a first demonstration of the tissue localization of the NTs in the human cerebellum from perinatal to adult age, thus suggesting their involvement in the development, differentiation and maintenance of the cerebellar connectivity. Codistribution of the four NTs or sets of them was observed in cortical and deep nuclei neurons. Multiple trophic roles for NTs, encompassing the classic target-derived and local mechanisms of support, are envisaged as significant in development, differentiation, and maintenance of the human cerebellar connectivity.     

显微定量法测定中成药中猪牙皂的含量

目的 :制定猪牙皂在脐风散与惊风散中的显微定量标准。方法 :用显微定量法 ,以猪牙皂特有的石细胞为显微特征物 ,对脐风散与惊风散中的猪牙皂进行测定。结果 :猪牙皂含量与每毫克特征数呈显著的线性正相关 ,回归方程为 y =61 .42 x -1 .1 0× 1 0 - 3(γ=1 .0 0 ,α=0 .0 5 )。结论 :显微定量法测定脐风散与惊风散中猪牙皂的含量是可行的 ,结果可靠     

老年病人睡眠状况及护理干预研究进展

综述了老年人睡眠质量及其影响因素、睡眠障碍的危害、老年病人睡眠的护理干预。建议进行前瞻性干预试验,为改善老年人的睡眠质量提供依据。     

葡萄球菌属对常用抗生素耐药情况调查

目的：了解葡萄球菌属，特别是耐甲氧西林葡萄球菌（MRS）的耐药情况，为临床用药提供参考。方法：从2002年1－7月送检的住院病人的血、痰、脓液、分泌物等标本中分离出的金黄色葡萄球菌、表皮葡萄球菌及其他血浆凝固酶阴性的葡萄球菌共105株，并进行药敏和多重耐药分析。结果：MRS的分离率较高，为68．6％，耐甲氧西林金黄色葡萄球菌（MRSA）为69．2％；耐甲氧西林表皮葡萄球菌（MRSE）为63．3％。MRS较非耐甲氧西林葡萄球菌（MSS）耐药率明显高，且MRS比MSS多重耐率高得多；MRSA对四种不同作用机制的抗生素；泰能、阿米卡星、环丙沙星、复方新诺明具有很高的多重耐药率，达到50％以上。结论：鉴于MRS的高分离率和多重耐药率，在治疗感染性疾病时，应加强病原学检查，提高标本鉴定的阳性率；在有效的治疗MRS感染的同时还应注意遏制MRS的产生。