Cholesterol storage and tau pathology in Niemann-Pick type C disease in the brain

Niemann-Pick type C disease is an inherited neurovisceral storage disorder with intracellular accumulation of cholesterol. In affected brains, many ballooned neurons are seen. Considerable nerve cell loss of unknown pathogenesis leads to neurological deterioration and dementia. Chemical examination of brains has failed to demonstrate increased levels of cholesterol. Using filipin fluorometry of neuronal cells in tissue slices, we found massive accumulation of cholesterol in neurons in four out of five human Niemann-Pick type C cases including adult patients. Neurofibrillary tangles composed of aggregates of the otherwise highly soluble protein tau were present in three Niemann-Pick type C cases and were also immunologically identical to those associated with Alzheimer's disease. However, only a thin slab of spinal cord or a tiny piece of isocortex was available for examination in the two cases without tangles. In a further semi-quantitative analysis of 576 neurons, we determined higher cholesterol content in tangle-bearing neurons than in adjacent tangle-free neurons. The association of cholesterol accumulation with neurofibrillary degeneration in Niemann-Pick type C disease and Alzheimer's disease awakens interest in the role of impaired cholesterol metabolism in the development of neurofibrillary tangles in both diseases.     

肺系病证瘀热病机探讨

肺系疾病在病变过程中存在着瘀热蕴结的病机特点。其病因常为邪热蕴肺,蒸液成痰,热伤血脉,血滞为瘀;病理因素主要为瘀热,常兼夹痰热、火热、毒热为患;瘀热相搏,阻于肺络,络伤血溢,可致出血之变;痰热瘀阻,目久可耗伤气阴或正虚邪恋,使病情迁延不愈。     

Effects of GTW treatment on proteinuria and acute glomerular immune lesion in experimental mesangial proliferative glomerulonephritis

Tripterygium wilfordii Hook.f.is a well-knownimmunosuppressive Chinese herb.The mainactivecomponents fromthis herb is a stable glycoside ,called multi-glycoside ofTripterygium wilfordiiHook.f. ( GTW) [1] , which has been widelyusedfor treatment of a variety of autoimmune dis-eases ,such as rheumatoid arthritis [2] ,glomeru-lonephritis (GN) [3] and systemic lupus erythe-matosus (SLE) [4] .GTWhas been reported to be beneficial tothe treatment of several types of nephritis .It couldeffectiv…     

预处理和贮藏条件对脱水甘蓝表面返霜的影响

添加葡萄糖的脱水甘蓝在贮藏过程中葡萄糖极易从甘蓝内部迁移到表面．实验结果表明，渗糖处理时添加一定量的乳糖和高麦芽糖浆代替葡萄糖，对延长脱水甘蓝的返霜期有良好的效果，高麦芽糖浆对延长脱水甘蓝返霜的效果明显好于乳糖．实验还研究了热烫时间、贮藏环境的相对湿度对葡萄糖迁移影响的规律．热烫90s、贮藏在较低的环境湿度下均有利于延长脱水甘蓝的返霜天数．     

Expression of two isozymes of acyl-coenzyme A: Cholesterol acyltransferase-1 and -2 in clear cell type renal cell carcinoma

Objectives:   The present study investigated the expression of acyl-coenzyme A: cholesterol acyltransferase-1 (ACAT-1) and -2 in clear cell type renal cell carcinoma (RCC).
Methods:   Clear cell type RCC and corresponding normal kidney tissue samples were obtained from 19 surgical cases (28–85 years of age). Tissue extracts were assayed for ACAT activity and protein expression by immunoblotting with anti-ACAT-1 and anti-ACAT-2 antibodies. Frozen sections were subjected to Oil red O staining for lipids, and were immunostained with ACAT-specific antibodies.
Results:   Acyl-coenzyme A cholesterol acyltransferase activity was 5.7-fold higher ( P  < 0.01) in clear cell carcinoma (23.52 ± 4.90 pmol/mg protein/min) than in normal kidney (4.12 ± 0.36). Consistent with this, immunoblotting and immunohistochemical staining revealed strong expression of ACAT-1 in clear cell type RCC. Densitometric analysis showed that ACAT-1 expression was 2.9-fold higher in clear cell type RCC than in normal kidney. In contrast, ACAT-2 expression was negative in clear cell type RCC and normal kidney. Oil red O staining showed massive deposits of lipid in RCC cells.
Conclusions:   We identified strong expression of ACAT-1 in clear cell type RCC. Upregulation of ACAT-1 leads to high ACAT enzymatic activity, which accelerates the accumulation of cholesterol ester in clear cell type RCC.     

Insulin detemir under steady-state conditions: no accumulation and constant metabolic effect over time with twice daily administration in subjects with Type 1 diabetes.

AIMS: This study investigated the pharmacodynamic and pharmacokinetic characteristics of the novel long-acting insulin analogue insulin detemir (IDet) under single-dose and steady-state conditions in comparison with those of NPH insulin at steady state. METHODS: Twenty-five subjects with Type 1 diabetes [seven females, 18 males, mean age (+/- sd) 39 +/- 12 years, body mass index 24 +/- 3 kg/m(2)] participated in three 24-h glucose clamps. IDet or NPH were given at 12-h intervals in fixed, individualized doses. The first clamp assessed the metabolic effect of NPH at steady state, the second investigated the effect of two single injections of IDet. Subjects continued IDet treatment for 7-14 days, after which the third clamp was performed to investigate IDet at steady state. RESULTS: At steady state, the metabolic effect of IDet was constant over 24 h while a clear peak in the metabolic effect [expressed as glucose infusion rates (GIR)] was observed with NPH after each injection. The fluctuation in the metabolic effect (maximum GIR divided by the average of the GIR values at the interval ends) was significantly lower in the second 12 h of the experiments with IDet under steady-state conditions compared with NPH (fluctuation(12-24 h) 1.27 +/- 0.17 vs. 1.56 +/- 0.72, P < 0.05). The overall metabolic effect of IDet at steady state was comparable with that of NPH [GIR-area under curve (AUC)(0-24 h): 5697 +/- 1861 vs. 5929 +/- 1965 mg/kg] whereas a significantly lower effect (5187 +/- 1784 mg/kg, P = 0.01 vs. steady state) was observed following the first two IDet injections. GIR values at the end of clamp day 2 (first doses) and clamp day 3 (steady state) were comparable [GIR(trough 24 h) 3.7 +/- 1.7 vs. 3.8 +/- 1.6 mg/(kg x min) NS], indicating that IDet had reached steady state after the first two injections. CONCLUSIONS: IDet administered twice daily reached steady state after the second injection and showed a constant metabolic effect over time under steady-state conditions. This should facilitate basal insulin substitution and decrease the risk of hypoglycaemia in insulin-treated subjects.     

Intellectual and adaptive behaviour functioning in pantothenate kinase-associated neurodegeneration

Background Pantothenate kinase‐associated neurodegeneration (PKAN), an extremely rare autosomal recessive disorder resulting in iron accumulation in the brain, has a diverse phenotypic expression. Based on limited case studies of one or two patients, intellectual impairment is considered part of PKAN. Investigations of cognitive functioning have utilized specific neuropsychological tests, without attention to general intellectual skills or adaptive behaviour. Methods Sixteen individuals with PKAN completed measures of global intellectual functioning, and participants or care providers completed measures of adaptive behaviour skills and day‐to‐day functional limitations. Clinicians provided global ratings of condition severity. Results Testing with standardized measures documented varied phenotypic expression, with general cognitive skills and adaptive behaviour ranging from high average to well below average. Age of disease onset correlated with measures of intellectual functioning, adaptive functioning and disease severity. Conclusions Findings support previously described clinical impressions of varied cognitive impairment and the association between age of onset and impairment. Further, they add important information regarding the natural history of the disease and suggest assessment strategies for use in treatment trials.     

Accumulation of PBDE-47 in primary cultures of rat neocortical cells.

A number of recent studies have examined the neurotoxic actions of polybrominated diphenyl ethers (PBDEs) using in vitro cell culture models. However, there are few data reporting the final concentration of PBDEs in cells after in vitro exposure to these compounds. To address this issue, the present study examined the concentration-dependent and time-dependent accumulation of 2,2',4,4'-tetrabromodiphenyl ether (PBDE-47) in primary cultures of rat neocortex. Mixed cultures of neuronal and glial cells were prepared from the neocortex of newborn rats and grown for 7 days in vitro. The cells were then exposed to freshly prepared serum-free culture medium containing (14)C-PBDE-47. Radiolabel associated with the cells or remaining in the medium was determined by liquid scintillation spectrometry. Exposure to 0.01-3.0 microM PBDE-47 for 60 min resulted in a concentration-dependent accumulation in cells. At each concentration, approximately 15% of the applied PBDE-47 was associated with the cells, resulting in a 100-fold magnification of the applied concentration (e.g., a 60-min exposure to 1 microM resulted in an approximate 100 microM concentration in the cells); 55% of the PBDE remained in the medium and 30% was associated with the plastic culture dish. Exposure to 1 microM PBDE-47 resulted in a linear increase in PBDE-47 in cells with time for the first 60 min, which began to saturate at 120 min. Addition of serum proteins to the medium decreased accumulation; at 10% serum in the medium, only 3% of the applied PBDE-47 was associated with the cells and 96% remained in the media after 60 min. The total volume of exposure also influenced accumulation of PBDE-47. Doubling the volume of serum-free exposure medium (from 2 ml to 4 ml) but leaving the concentration constant (1 microM) resulted in a 1.5-fold increase in PBDE-47 concentration in the cells. These data show that a number of factors, including duration of exposure, volume of exposure, and concentration of serum proteins in the medium, can influence the accumulation of PBDE-47 in cells in vitro. For this highly lipophilic compound, use of medium concentration underestimates tissue concentration by up to two orders of magnitude. Thus, accurate information on the tissue concentration for in vitro experiments should be determined empirically.     

上海市二、三级医院品牌现状分析及其影响因素

通过对上海市二、三级医院的调查,分析了上海市二、三级医院的品牌现状,并且从医院内部因素、外部因素、医院品牌历史沉积三方面对影响医院品牌的因素进行了分析总结.