实验性大鼠液压分级颅脑损伤模型的建立与研究

用自制液压冲击颅脑损伤仪对大鼠的头部由轻到重的４种冲击力产生４级脑损伤。１级可以无明显病理生理变化；２～４级则随冲击力的加重病理生理变化亦加重。这些变化包括心率，呼吸，血压，颅内压，脑水份含量与伊文思蓝蓝染范围测定以及病理学的变化。     

Using a supervisory framework to support and evaluate a multiproject practice development programme

? The paper describes a multiproject practice development programme undertaken over a period of 1 year. ? The background and development of the programme are outlined, whilst attention is paid to the innovatory nature of the work, particularly the use of inductive, deductive and integrated approaches to both change implementation and project supervision. ? The programme was monitored throughout using different data sources and the paper uses evaluative material retrospectively to provide answers to organizational and professional difficulties which arose during the course of the programme. ? The authors conclude that the use of combinations of different models for practice development has potential, but requires careful supervision. ? They also recommend that those involved in practice development are made fully aware of its local or micropolitics, and develop strategies to deal with change before it occurs, not after it has taken place.     

Evaluating risk factors associated with severe hypoglycaemia in epidemiology studies—what method should we use?

AIMS: To determine the most appropriate regression models to use when assessing risk factors for severe hypoglycaemia and to investigate the impact of model misspecification and its clinical implications. METHODS: A total of 1229 children with Type 1 diabetes (mean age 11.7 years sd 4.1), of which 605 (49.2%) were males, were studied. Prospective assessment of severe hypoglycaemia (an event leading to loss of consciousness or seizure) was made over the 9-year period, 1992-2001. Patients were seen every 3 months and episodes of hypoglycaemia along with clinical data were recorded. Over 70% of children never experienced a severe hypoglycaemic event. Data were analysed using the Poisson regression, negative binomial, zero-inflated Poisson (ZIP) and zero-inflated negative binomial (ZINB) models. The over-dispersion and likelihood ratio statistics were calculated and the analytical methods compared. RESULTS: The Poisson regression model did not fit the data well. The negative binomial and the zero inflated Poisson and negative binomial models fitted the data better than Poisson. CONCLUSIONS: The commonly used Poisson regression models to analyse hypoglycaemia epidemiology may lead to biased parameter estimates and incorrect determination of risk factors for hypoglycaemia. We recommend the use of the negative binomial or zero inflated models to examine any risk factors associated with severe hypoglycaemia. Careful consideration must be given to the interpretation of hypoglycaemia surveys and their analysis.     

Genetic contributions to Parkinson's disease

Sporadic Parkinson's disease (PD) is a common neurodegenerative disorder, characterized by the loss of midbrain dopamine neurons and Lewy body inclusions. It is thought to result from a complex interaction between multiple predisposing genes and environmental influences, although these interactions are still poorly understood. Several causative genes have been identified in different families. Mutations in two genes [α-synuclein and nuclear receptor-related 1 (Nurr1)] cause the same pathology, and a third locus on chromosome 2 also causes this pathology. Other familial PD mutations have identified genes involved in the ubiquitin–proteasome system [parkin and ubiquitin C-terminal hydroxylase L1 (UCHL1)], although such cases do not produce Lewy bodies. These studies highlight critical cellular proteins and mechanisms for dopamine neuron survival as disrupted in Parkinson's disease. Understanding the genetic variations impacting on dopamine neurons may illuminate other molecular mechanisms involved. Additional candidate genes involved in dopamine cell survival, dopamine synthesis, metabolism and function, energy supply, oxidative stress, and cellular detoxification have been indicated by transgenic animal models and/or screened in human populations with differing results. Genetic variation in genes known to produce different patterns and types of neurodegeneration that may impact on the function of dopamine neurons are also reviewed. These studies suggest that environment and genetic background are likely to have a significant influence on susceptibility to Parkinson's disease. The identification of multiple genes predisposing to Parkinson's disease will assist in determining the cellular pathway/s leading to the neurodegeneration observed in this disease.     

Acute effects of high-dose thyrotropin releasing hormone infusions in Alzheimer's disease

Thyrotropin releasing hormone (TRH) was administered intravenously to ten patients with Alzheimer's Disease (AD) in a high-dose paradigm, thought to maximize central nervous system effects and potentially produce facilitation of cholinergic function, a known property of the neuropeptide. Acute effects of TRH on behavioral, cognitive and physiologic measures were assessed after patients received 0.1 mg/kg TRH, 0.3 mg/kg TRH and placebo, the higher TRH dose and placebo being given in a randomized, double-blind fashion. Patients showed statistically significant increases in arousal and improvement in affect, as well as a modest improvement in semantic memory, all after receiving the higher TRH dose. Both TRH doses produced transient rises in systolic blood pressure, with no effect on diastolic blood pressure, heart rate or temperature. This study suggests that high-dose TRH can be safely administered to AD patients and is neurobehaviorally active; further studies are needed to determine the extent and mechanism of the cognitive and psychobiological properties of this peptide in AD and other neuropsychiatric disorders.     

Studies on the effects of Pluchea indica less root extract on gastroduodenal ulcer models in rats and guineapigs

The methanolic fraction of P. indica root extract was found to possess significant antiulcer activity in different experimental animal models. In preventive antiulcer tests, significant protective actions in acetylsalicylic acid, serotonin and indomethacin-induced gastric lesions were observed in experimental rats. The extract also afforded significant protection to chemically-induced duodenal lesion in guineapigs. Significant enhancement of healing process in acetic acid-induced chronic gastric lesions were also observed in the extract-treated animals.     

新胆碱酯酶抑制剂对实验性重症肌无力的治疗作用

本文应用实验性重症肌无力模型研究了7种新的胆碱酯酶抑制剂对实验性重症肌无力的治疗作用,其中包括6种二甲氨基甲酸烷氧(烷硫)基苯酯及1种中草药提取物,大多数化合物对乙酰胆碱酯酶有较强的抑制作用,并见到有不同程度的治疗效果。二甲氨基甲酸-3-叔丁基-4〔2-(1-哌啶基)乙氧基〕苯酯不仅明显改善肌无力症状,而且毒性小、副作用较新斯的明轻,值得进一步研究。     

急性软脑膜微循环障碍实验模型的研究

本文报道应用高分子右旋糖酐制成软脑膜微循环障碍的动物实验模型。软脑膜微循环障碍模型的标志;软脑膜微血管血流速度减慢,血液流态呈粒状流或絮状流,血细胞聚集。 将98只家兔分成甲、乙二组。甲组38只,静脉注射平均分子量为25万的高分子右旋糖酐,乙组60只,静脉注射平均分子量为49万的高分子右旋糖酐。实验结果发现,甲组38只家兔仅28只可复制成软脑膜微循环障碍的实验模型,模型复制成功率为73.6％;乙组60只家兔,59只可形成软脑膜微循环障碍实验模型,成功率为98.3％。本实验证明复制动物模型以49万分子量的高分子有旋糖酐为宜。 本实验模型可用于脑微循环障碍和改善脑微循环药物的研究工作。     

糖尿病是一种心血管疾病和心身疾病的观点探讨

本文就糖尿病患者最早就诊的是心血管内科医师,以及负性情绪可明显影响糖尿病的发展进行了分析,并提出改善心境可明显增加自我控制糖尿病的能力。     

High-resolution imaging of progressive articular cartilage degeneration.

The objective of this study was to develop and verify a new technique for monitoring the progression of osteoarthritis (OA) by combining a rat model with the imaging modality optical coherence tomography (OCT). Time-sequential, in vivo, OCT imaging was performed on the left femoral condyles of 12 Wistar rats following sodium-iodoacetic acid-induced OA progression. The right femoral condyles (untreated) were also imaged and served as controls. Imaging was performed on days 0, 10, 20, 30, and 60 with an OCT system capable of acquiring images at four frames per second and an axial resolution of 5 microm. Progressive changes were analyzed using an OA scoring system. OCT successfully identified progressive cartilage degeneration as well as alteration of the cartilage/bone interface. Significant changes to both of these structures were observed in the sodium-iodoacetic acid-injected condyles. Structural changes detected with OCT were confirmed histologically. OCT in combination with a well-known model used in arthritis research represents a powerful tool for following degenerative joint disease progression in a given animal by detecting changes to the cartilage/bone interface and articular cartilage.