补肾健脾活血汤治疗绝经后骨质疏松症33例

目的：观察自拟补肾健脾活血汤治疗绝经后骨质疏松症的临床疗效。方法：将66例绝经后骨质疏松症患者随机分为治疗组与对照组,每组33例。治疗组予补肾健脾活血汤口服,每日1剂,水煎服;对照组予复方氨基酸螯合钙胶囊（乐力）口服,每天1粒。两组疗程均为6个月。比较两组治疗前后桡骨远端1／3骨密度与临床疗效。结果：治疗组临床疗效和止痛效果明显优于对照组（P〈0．05）。两组治疗后骨密度均显著提高,治疗组骨密度提高程度优于对照组（P〈0．05）。结论：补肾健脾活血汤对绝经后骨质疏松症具有较好的止痛效果,并能有效提高骨密度。     

ω-3长链多不饱和脂肪酸对培养的少突胶质前体细胞的影响

目的 探讨长链多不饱和脂肪酸(LPFA)对体外培养的成年海马少突胶质前体细胞(OPC)的存活及突起生长影响.方法 采用成组设计,使用从成年大鼠海马分离培养的两种神经祖细胞,分别经花生四烯酸(AA)、二十碳五烯酸(EPA)或二十二碳六烯酸(DHA)处理后,以乳酸脱氢酶(LDH)分析法测定细胞活性;再行免疫细胞荧光染色后做突起的定量测量.结果 EPA、DHA和AA在高浓度(50 μmol/L)时使海马硫酸软骨素蛋白聚糖(NG2)阳性OPC数虽显著增加(P<0.05),而EPA和DHA还可使OPC突起长度显著增长(P<0.05).结论 ω-3LPFA即EPA和DHA对OPC的增生和突起形成有促进作用.     

高浓度棕榈酸对正常肝细胞株糖皮质激素受体α-亚型表达的影响

目的：研究高浓度棕榈酸对肝细胞糖皮质激素受体α亚型（GRα）表达的影响。方法：用含有10%小牛血清的低糖DMEM培养基培养正常肝细胞株L02。1.0×105细胞接种到6孔板中,并用含有200 mmol/L棕榈酸的低糖DMEM培养基培养72 h,24 h换液1次,用实时荧光定量PCR进行定量分析GRαmRNA。结果：高浓度棕榈酸培养72 h后,肝细胞内GRαmRNA水平是对照组（用含10%、不含脂肪酸牛血清白蛋白的低糖DMEM培养基培养72 h）的1.67倍。结论：高浓度棕榈酸可以刺激肝细胞GRα上调表达。     

Effect of 8.5% and 25% caloric restriction on mitochondrial free radical production and oxidative stress in rat liver

Previous studies have consistently shown that 40% caloric restriction (CR) decreases the rate of mitochondrial ROS production and steady-state levels of markers of oxidative damage to macromolecules including mitochondrial DNA. However, few investigations have studied whether these changes also occur in lower CR regimes. This is of potential interest since moderate levels of dietary restriction are more practicable for humans. In this investigation male Wistar rats were subjected to 8.5% and 25% caloric restriction. Neither 8.5% nor 25% CR changed mitochondrial ROS production, oxygen consumption or mtDNA oxidative damage in rat liver mitochondria. However, both 8.5% and 25% CR significantly decreased the five different markers of protein oxidation, glycoxidation and lipoxidation measured, aminoadipic and glutamic semialdehyde, carboxyethyl-lysine, carboxymethyl-lysine, and malondialdehyde-lysine. The fatty acid composition of liver mitochondria was also affected and led to a moderate decrease in the degree of membrane unsaturation in both 8.5% and 25% CR. While 8.5% CR only affected complex I concentration (which was decreased), 25% CR decreased complexes I and IV and increased complexes II and III of the respiratory chain. Apoptosis-inducing factor (AIF) significantly decreased in 25% CR but not in 8.5% CR. The results show that moderate levels of caloric restriction can have beneficial effects including decreases in oxidative protein modification and a lower sensitivity of membranes to lipid peroxidation, in association with a reprogramming of the respiratory chain complexes and AIF content.     

Unique patient with cerebrotendinous xanthomatosis. Evidence for presence of a defect in a gene that is not identical to sterol 27-hydroxylase

Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive disorder believed to be exclusively caused by mutations in the CYP27A1 gene coding for the enzyme sterol 27-hydroxylase. Common findings in CTX are tendon xanthomas, cataracts and progressive neurological dysfunction. Here, we characterize an adult female patient with tendon xanthomas and classic biochemical findings of CTX (i.e. high levels of bile alcohols and cholestanol and extremely low levels of 27-hydroxycholesterol in plasma). Additionally, sterol 27-hydroxylase activity in cultured monocyte-derived macrophages from this patient was <5% of normal. Sequencing the CYP27A1 gene uncovered that the patient is heterozygous for two previously undescribed base substitutions in exon 8, C478A and C479A, which are expected to affect the haeme-binding domain of the enzyme. When expressed in HEK293 cells, the corresponding protein had only 8% of normal enzymatic activity. No other mutation was found in the open reading frame of the CYP27A1 gene, intron-exon boundaries or in the 5'-untranslated region up to 5000 bp distal to the translational start site. Sequencing mRNA isolated from leucocytes from the patient revealed a 1 : 1 ratio of mutated and nonmutated species, with total mRNA levels that were not significantly different from the controls. It is concluded that the patient is heterozygous for two mutations affecting one allele of the CYP27A1 gene and with at least one additional yet undefined gene that is of critical importance for the activity of sterol 27-hydroxylase.     

Protective effects of ursodeoxycholic acid on chenodeoxycholic acid-induced liver injury in hamsters

AIM To investigate the effects of ursodeoxycholic acid (UDCA) on chenodeoxycholic acid (CDCA)-induced liver injury in hamsters, and to elucidate a correlation between liver injury and bile acid profiles in the liver.METHODS Liver injury was induced in hamsters by administration of 0.5% (w/w) CDCA in their feed for 7 d.UDCA (50 mg/kg and 150 mg/kg) was administered for the last 3 d of the experiment.RESULTS At the end of the experiment, serum alanine aminotransferase (ALT) increased more than 10 times and the presence of liver injury was confirmed histologically. Marked increase in bile acids was observed in the liver. The amount of total bile acids increased approximately three-fold and was accompanied by the increase in hydrophobic bile acids, CDCA and lithocholic acid (LCA). UDCA (50 mg/kg and 150 mg/kg) improved liver histology, with a significant decrease (679.3 ±77.5 U/L vs 333.6 ± 50.4 U/L and 254.3 ± 35.5 U/L, respectively, P ＜ 0.01) in serum ALT level. UDCA decreased the concentrations of the hydrophobic bile acids, and as a result, a decrease in the total bile acid level in the liver was achieved.CONCLUSION The results show that UDCA improves oral CDCA-induced liver damage in hamsters. The protective effects of UDCA appear to result from a decrease in the concentration of hydrophobic bile acids, CDCA and LCA, which accumulate and show the cytotoxicity in the liver.     

Metabolic and functional profiling of the ischemic/reperfused rat retina

We quantitatively tracked the recovery in amino acid labeling and cation channel functionality within distinct retinal elements for up to 2 weeks after an ischemic insult. Pattern recognition analysis of multiple amino acid and agmatine (a cation channel probe; 1-amino-4-guanidobutane; AGB) immunocytochemical patterns was used to classify all neural elements within the retina. This classification was spatially complete and with single-cell resolution. By 48 hours of reperfusion the amino acid labeling pattern of virtually all cell populations had returned to near preischemic levels, with the exception of glutamine and alanine levels, which remained significantly higher in many cell populations. Classification resulted in a total of 18 statistically separable theme classes (including neurons, glia, and extraretinal classes), a reduction of 10 theme classes from the normal retina (Sun et al. [ 2007a, b] J Comp Neurol, this issue). In addition to the known selective losses of amacrine cell types within the inner nuclear layer, we now demonstrate a selective loss of theme classes representing cone bipolar cells within the bipolar cell population. While there was a recovery in the amino acid labeling pattern, there were persistent cation channel gating anomalies (as reflected by AGB labeling) within several theme classes, including the theme class representing all the remaining rod bipolar cells, suggesting aberrant neuronal function secondary to metabolic insult.     

Effect of the branched-chain alpha-keto acids accumulating in maple syrup urine disease on S100B release from glial cells

Accumulation of the branched-chain alpha-keto acids (BCKA), alpha-ketoisocaproic acid (KIC), alpha-keto-beta-methylvaleric acid (KMV) and alpha-ketoisovaleric acid (KIV) and their respective branched-chain alpha-amino acids (BCAA) occurs in tissues and biological fluids of patients affected by the neurometabolic disorder maple syrup urine disease (MSUD). The objective of this study was to verify the effect of the BCKA on S100B release from C6 glioma cells. The cells were exposed to 1, 5 or 10 mM BCKA for different periods and the S100B release was measured afterwards. The results indicated that KIC and KIV, but not KMV, significantly enhanced S100B liberation after 6 h of exposure. Furthermore, the stimulatory effect of the BCKA on S100B release was prevented by coincubation with the energetic substrate creatine and with the N-nitro-l-arginine methyl ester (l-NAME), a nitric oxide synthase inhibitor, indicating that energy deficit and nitric oxide (NO) were probably involved in this effect. Furthermore, the increase of S100B release was prevented by preincubation with the protein kinase inhibitors KN-93 and H-89, indicating that KIC and KIV altered Ca2+/calmodulin (PKCaMII)- and cAMP (PKA)-dependent protein kinases activities, respectively. In contrast, other antioxidants such as glutathione (GSH) and trolox (soluble vitamin E) were not able to prevent KIC- and KIV-induced increase of S100B liberation, suggesting that the alteration of S100B release caused by the BCKA is not mediated by oxidation of sulfydryl or other essential groups of the enzyme as well as by lipid peroxyl radicals. Considering the importance of S100B for brain regulation, it is conceivable that enhanced liberation of this protein by increased levels of BCKA may contribute to the neurodegeneration characteristic of MSUD patients.