Lithium prevents colchicine-induced apoptosis in rat cerebellar granule neurons

Objectives:  Here we evaluated the neuroprotective effects of two well-known mood stabilizers, lithium and valproic acid (VPA), against colchicine neurotoxicity in cerebellar granule cells (CGNs).
Methods:  The CGNs were differentiated for 7 days, pretreated with lithium or VPA for 24 h and after colchicine 1  μ M was added. Cellular damage was assessed with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium (MTT) method and apoptosis in CGNs was characterized by chromatin condensation and DNA fragmentation.
Results:  Incubation with lithium (1–5 mM) attenuated this apoptosis markedly, in a dose–dependent way however, the addition of VPA (0.5–2 mM) did not protect CGNs. Colchicine-induced apoptosis is mediated through the activation of caspase-3. An increase in caspase-3 activity was detected within 18 h and was blocked in presence of lithium 5 mM.
Conclusions:  Our data indicate that lithium treatment is selectively neuroprotective; however, in our experimental conditions VPA did not protect CGNs from apoptosis induced by colchicine. Our results support the hypothesis that distinct pathways mediate the neuroprotective effects of lithium and VPA.     

Chitotriosidase genotype and serum activity in subjects with combined hyperlipidemia: effect of the lipid-lowering agents, atorvastatin and bezafibrate

Chitotriosidase, an enzyme involved in the degradation of chitin-containing pathogens with unclear function in humans, has been proposed as a marker of lipid accumulation in macrophages in different lipid-storage diseases, including atherosclerosis. To evaluate (1) if lipid-lowering treatment could modify serum chitotriosidase activity and (2) be useful in monitoring lipid-lowering treatment, we have analyzed this enzyme activity in the participants in the Atozvastatin Versus Bezafibrate in Mixed Hyperlipidemia (ATOMIX) study, a double-blind, comparative, and randomized study comparing the efficacy of atorvastatin and bezafibrate in mixed hyperlipidemia. Because a common genetic deficiency of chitotriosidase modifies serum quitotriosidase activity, this genetic variation was also studied. Seven subjects of 116 (6.03%) were homozygous, and 46 (39.6%) were heterozygous for the defective allele. Mean serum quitotriosidase activity correlated with allele dosage, as it was found to be of 0, 59.8 +/- 52.6 and 81.2 +/- 41.6 nmol/mL/h, in homozygotes for the defective allele, heterozygotes, and homozygotes for the wild-type allele, respectively (P =.0011 for the difference between the last 2 groups). However, this enzyme activity was not found to correlate with lipid levels before and after treatment with either atorvastatin or bezafibrate, and neither with the intensity of the lipid lowering. These results do not support the use of serum chitotriosidase activity as a biologic marker of atherosclerotic plaque modification related to hypolipidemic treatment.     

Orphenadrine prevents 3-nitropropionic acid-induced neurotoxicity in vitro and in vivo

1. Previous studies indicate that 3-nitropropionic acid (3-NPA) neurotoxicity involves the excitotoxic activation of N-methyl-D-aspartate (NMDA) receptors. Thus, we examined the effect of orphenadrine (an anticholinergic drug with NMDA receptor antagonist properties) on 3-NPA neurotoxicity in both cultured rat cerebellar granule cells (CGCs) and in rats. 2. Orphenadrine protected CGCs from 3-NPA-induced mortality, as assessed by both the neutral red viability assay and laser scanning cytometry, using propidium iodide staining. 3. For rats, two indirect markers of neuronal damage were used: the binding of [(3)H]-PK 11195 to the peripheral-type benzodiazepine receptor (PBR), a microglial marker, and expression of the 27 kD heat-shock protein (HSP27), a marker of activated astroglia. Systemic administration of 3-NPA (30 mg kg(-1) per day for 3 days) induced a 170% increase in [(3)H]-PK 11195 binding, and expression of HSP27. 4. Both the increase in [(3)H]-PK 11195 and HSP 27 expression were prevented by previous administration of 30 mg kg(-1) per day of orphenadrine for 3 days. Lower doses (10 and 20 mg kg(-1)) had no protective effect. Orphenadrine also reduced 3-NPA-induced mortality in a dose-dependent manner. 5. We propose that orphenadrine or orphenadrine-like drugs could be used to treat neurodegenerative disorders mediated by overactivation of NMDA receptors.     

Multicore myopathy with restrictive cardiomyopathy

A 10-y-old girl is presented who suffered mild muscular weakness and exercise intolerance from the age of 1 y onwards, with progression appearing from the age of about 8 y. Multicore myopathy and restrictive cardiomyopathy were diagnosed. Literature concerning the coexistence of multicore myopathy and cardiomyopathy is reviewed.     

The effect of changes in dietary fat on the food group and nutrient intake of 4- to 10-year-old children

OBJECTIVE: To determine how young children changed their overall diet when they changed their fat intake after 3 months of participating in a nutrition education demonstration study designed to lower low-density lipoprotein cholesterol and cardiovascular risk. METHODS: Three 24-hour dietary recalls were collected from 303 4- to 10-year-old children at baseline and 3 months later. At both times, mean number of servings from food groups, grams of fat contributed from food groups, and intake of calories and nutrients were calculated and compared among quartiles of children formed according to change in their percent of calories from total fat after 3 months. RESULTS: Children who reduced their percent of calories from total fat most (ie, by an average of 8.5%) after 3 months consumed fewer servings from meats, eggs, dairy, fats/oils, and breads but tended to increase their number of servings from lower-fat foods within those food groups, particularly from dairy foods. These children also increased their mean intake of fruits, vegetables, and desserts, and maintained average intakes of all nutrients (except vitamin D) in excess of two thirds of the respective recommended dietary allowance. CONCLUSIONS: Young children who reduced their percent of calories from total fat in accordance with the current National Cholesterol Education Program recommendations accomplished this by reducing their overall intake of higher-fat foods, replacing higher-fat foods with lower-fat foods within several food groups, particularly within the dairy group (eg, drinking skim milk instead of whole milk) and by consuming more servings of fruits, vegetables, and very-low-fat desserts. These behaviors did not compromise their mean calorie or nutrient intakes, showing that it is possible for young children to lower their fat intake safely to reduce their risk of future heart disease.     

Cyclic food restriction, insulin and mammary cell proliferation in the rat

We reported recently that weight cycling significantly increased the incidence of mammary cancer in virgin female rats that were pretreated with N-methyl-N-nitrosourea. The present study investigated the effect of weight cycling on mammary epithelial cell proliferation and its relationship to changes in plasma insulin, estrogen, progesterone and urinary corticosterone in 30 female virgin Sprague-Dawley rats. Animals were fed a modified AIN-76A diet containing 24.6% corn oil by weight. Weight-cycled (WC) rats were food restricted daily by either 33% or 50% of non-restricted controls for 1 week followed by 3 weeks compensatory refeeding and weight recovery over 18 weeks or 4.5 weight cycles. WC rats consumed 6-10% less food than controls (P = 0.01) but showed a 71- 89% greater efficiency of food utilization for growth (P < 0.0001) than controls. There were no differences in total weight gain during treatment. Mammary lobuloalveolar and ductal cell proliferation of WC rats, measured by 5-bromo-2'deoxyuridine labelling, increased in a dose- response fashion, P = 0.03, P = 0.06 respectively in comparison to controls. Energy and substrate utilization measured by indirect calorimetry indicated WC animals expended less energy (P = 0.005) and utilized less glucose (P = 0.0001) and protein (P = 0.006) during restriction, and less lipid during recovery (P = 0.05) than controls. There were no significant differences in hormone levels between groups. Multiple regression analysis with plasma insulin, estrogen, progesterone and urinary corticosterone as independent variables (r = 0.947, r2 = 0.897, P = 0.003) showed that plasma insulin was the only significant predictor (P < 0.01) of mammary cell proliferation. In accord with this observation, tyrosine-phosphorylated activation of insulin receptor substrate-1, detected by immunoprecipitation and Western immunoblot analysis in mammary tumors of WC rats from our previous study, was 3-5 times greater than in non-restricted controls (P < 0.01). Present findings suggest that weight cycling in rats increases risk of breast cancer development via insulin stimulated mammary cell proliferation.      

长茎金耳环脂溶性化学成分的研究

目的 对长茎金耳环根及根茎的化学成分进行研究。方法 采用溶剂法和色谱法分离化合物，波谱法鉴定化合物的结构。结果 从长茎金耳环根及根茎的乙醇提取物中分离得到9个化合物，经波谱分析确定它们分别是（2E，6Z，8E）－N－异丁基－2，6，8－三烯十酰胺（spilanthol,I)、magnosalin(Ⅱ）、heterotropan(Ⅲ)、N－异丁基－3，4－亚甲二氧基肉桂酰胺（N-isobutyl-3,4-methylenedioxy cinnamide,Ⅳ)、马兜铃内酰胺I（aristololactam I,Ⅴ)、胡萝卜苷（daucosterol,Ⅵ)、7－甲氧基马兜铃内酰胺Ⅳ（7－methoxyaristololactam Ⅳ,Ⅶ)、马兜铃酸I（aristolochic acid I,Ⅷ)和香草酸（vanillic acid,Ⅸ)。结论 这些化合物均为首次从长茎金耳环中分离得到，其中I和Ⅱ为首次从细辛属植物中分离得到。