肾脏疾病儿童血浆促酰化蛋白水平测定的意义

目的 探讨肾脏疾病儿童血浆促酰化蛋白(ASP)与血浆C,、非酯化脂肪酸(NEFA)及血脂的关系.方法 肾脏疾病组48例,健康对照组279例.将48例肾脏疾病儿童分为3组:1.急性链球菌感染后肾小球肾炎(APSGN)组12例;2.狼疮性肾炎(LN)组4例;3.肾病综合征(Ns)组32例.用ELISA方法 检测各组血浆ASP水平,酶学比色法测定其NEFA水平,用酶学比浊法检测其血浆C3、血脂等生化指标.数据采用GraphPad Prism 4.0软件进行统计学分析.结果 1.APSGN组(81.8±24.8)nmol/L、LN组(90.9 ±28.2)nmoL/L和Ns组(101.4 ±399)nmolL血浆ASP水平明显高于健康对照组[(44.3±25.2)mnol/L P.<0.01];APSGN和LN组血浆C3,水平均低于健康对照组(Pa<0.05),Ns组与健康对照组比较C3,无明显变化.2.肾脏疾病各组存在一定程度血脂代谢紊乱.APSGN组血浆三酰甘油(TG)水平高于健康对照组,但无统计学差异(P>0.05),而高密度脂蛋白胆固醇(HDL-C)显著低于健康对照组(P<0.001).LN和NS组存在显著高TG、高TC和高低密度脂蛋白胆固醇(LDL-C)血症,LN组患儿还存在低血浆HDL-C水平(P<0.001),载脂蛋白(Apo)A和ApoB升高仅见于Ns组(P<0.01,0.001);各组NEFA水平无显著变化.3.肾脏疾病患儿血浆ASP水平与TG(r=0.301 P相似文献   

Role of cholesterol ester mass in regulation of secretion of ApoB100 lipoprotein particles by hamster hepatocytes and effects of statins on that relationship

Our understanding of the factors that regulate the secretion of apoB100 lipoproteins remains incomplete with considerable debate as to the role, if any, for cholesterol ester in this process. This study examines this issue in primary cultures of hamster hepatocytes, a species in which both cholesterol and apoB100 metabolism are very similar to man. Addition of oleate to medium increased the mass of triglyceride and cholesterol ester within the hepatocyte and also increased the secretion of triglycerides, cholesterol ester, and apoB100 into the medium. Next, the responses of hamster hepatocytes to addition of either an HMG-CoA reductase inhibitor (lovastatin) or an acyl-CoA cholesterol acyltransferase inhibitor (58-035) to the medium, with or without added oleate, were determined. Effects of either agent were only evident in the oleate-supplemented medium in which cholesterol ester mass had been increased above basal. If oleate was not added to the medium, neither agent reduced apoB100 secretion; equally important, over the 24-hour incubation, neither agent, at the concentration used, produced any detectable change in intracellular cholesterol ester mass. However, in contrast to the estimates of mass, which were unchanged, under the same conditions radioisotopic estimates of cholesterol ester synthesis were markedly reduced. Any conclusion as to the relation of cholesterol ester mass to apoB100 secretion would therefore depend on which of the 2 methods was used. Overall, the data indicate a close correlation between the mass of cholesterol ester within the hepatocyte and apoB100 secretion from it and they go far to explain previous apparently contradictory data as to this relation. More importantly, though, taken with other available data, they indicate that the primary response of the liver to increased delivery of lipid is increased secretion rather than decreased uptake. These results point, therefore, to a hierarchy of hepatic responses to increased flux of fatty acids and increased synthesis of cholesterol that in turn suggests a more dynamic model of cholesterol homeostasis in the liver than has been appreciated in the past.     

Recombinant C3adesArg/acylation stimulating protein (ASP) is highly bioactive: A critical evaluation of C5L2 binding and 3T3-L1 adipocyte activation

C5L2 is a recently identified receptor for C5a/C5adesArg, C3a and C3adesArg (ASP). C5a/C5adesArg bind with high affinity, with no identified activation. By contrast, some studies demonstrate C3a/ASP binding/activation to C5L2; others do not. Our aim is to critically evaluate ASP/C3adesArg-C5L2 binding and bioactivity.Cell-associated fluorescent-ASP (Fl-ASP) binding to C5L2 increased from transiently transfected < stably transfected < Fl-ASP-sorted C5L2-HEK for both human C5L2 and mouse C5L2. Transfected C5L2-CHO cells had similar results. Endogenous C5L2 expression increased from 3T3-L1 preadipocytes < 3T3-L1 adipocytes < primary mouse adipocytes. Non-transfected cells ± Fl-ASP demonstrated background fluorescence only.In adherent C5L2-HEK (Fl-ASP sorted) and 3T3-L1 cells, blocking with 10% fetal calf serum, protamine sulfate or ovalbumin prevented ¹²⁵I-ASP non-specific binding (NSB, no cells), while albumin increased NSB. Binding to non-transfected HEK was comparable to NSB. Optimal specific binding was obtained at 20 °C (vs. 4 °C) in PBS or serum-free medium with K_d 83.7 ± 23.7 nM (C5L2-HEK), 66 ± 15 nM (C5L2-CHO) and 76 ± 14.3 nM (3T3-L1 preadipocytes); ¹²⁵I-C5a binding had greater affinity. Fl-ASP-C5L2 binding was comparable and concentration dependent (K_d 31 nM (direct binding) and IC₅₀ 35 nM (competition binding) regardless of conditions).Recombinant ASP (rASP) produced in modified Escherichia coli Origami (DE3) (allowing folding and disulphide bridge formation), purified under non-denaturing conditions demonstrated 10× greater bioactivity vs. proteolytically derived plasma ASP for triglyceride synthesis and fatty acid uptake in 3T3-L1 adipocytes and preadipocytes while adipose tissue from C5L2 KO mice was non-responsive. rASP stimulation of adipocyte BODIPY-fatty acid uptake demonstrated EC₅₀ 115 ± 93 nM and maximal stimulation of 413 ± 33%, p < 0.001. ASP binding has distinct characteristics that lead to C5L2 activation and increased bioactivity.     

Throat Infection, Neck and Chest Pain and Cardiac Response： A Persistent Infection-Related Clinical Syndrome

Dizziness, chest discomfort, chest depression and dyspnea are a group of symptoms that are common complaints in clinical practice. Patients with these symptoms are usually informed that while neurosis consequent to coronary heart disease is excluded nonetheless they remain unhealthy with no rational explanation or treatment. 165 cases of these symptoms and 85 control subjects were reviewed and underwent further medical history inquiry, routine EKG test and cardiac ultrasound examination. Thirty-five patients received coronary artery angiography to exclude coronary heart disease. Serum myocardial autoantibodies against beta1-adrenoceptor, alpha-myosin heavy chain, M2-muscarinic receptor and adenine-nucleotide translocator were tested, and inflammatory cytokines and high sensitivity C-reaction protein were measured and lymphocyte subclass was assayed by flow cytometry. All patients had a complex of four symptoms or tetralogy： （1） persistent throat or upper respiratory tract infection, （2） neck pain, （3） chest pain and （4） chest depression or dyspnea, some of them with anxiety. Anti-myocardial autoantibodies （AMCAs） were present in all patients vs. 8% in controls. TNF-α, IL-1 and IL-6 were significantly higher in patients than in controls （P〈0.01）. CD3^＋ and CD4-CD8^＋ lymphocytes were significantly higher and CD56＋ lymphocytes lower in patients than those in controls （P〈0.01）. The ratio of serum pathogen antibodies positive against Coxsackie virus-B, cytomegalovirus, Mycoplasma pneumoniae and Chlamydia pneumoniae were all markedly higher in patients. These data led to identification of a persistent respiratory infection-related clinical syndrome, including persistent throat infection, neck spinal lesion, rib cartilage inflammation, symptoms of cardiac depression and dyspnea with or without anxiety.     

An investigation of hormone and lipid associations after weight loss in women

OBJECTIVE: The objectives of this study were to determine 1) whether the extent of weight loss is predictive of the degree of changes in hormone and lipid levels; 2) the interactions between energy regulating hormones after weight loss through an energy deficit/exercise protocol diet and exercise; 3) whether initial metabolic parameters are indicative of the extent of weight loss. METHODS: Thirty-five hyperlipidemic females (BMI 28-39 kg/m2) 35-60 years old participated in a six month weight loss trial. Weight loss resulted from a diet and exercise program that when combined produced a 30% energy deficit. Fasting plasma taken during 2 wk stabilization periods at the beginning and end of the study was analysed for lipids, hormone and glucose levels. RESULTS: Average weight loss was 11.7 +/- 2.5 kg (p < 0.0001). TC, LDL-C, and triacylglycerols decreased 9.3 +/- 9.5% (p < 0.0001), 7.4 +/- 12.2% (p < 0.001), and 26.8 +/- 19.6% (p < 0.05), respectively, while HDL-C increased (p < 0.05) by 8.2 +/- 16.3%. Leptin levels declined (p < 0.001) 48.9 +/- 16.0% and ghrelin levels rose (p < 0.001) 21.2 +/- 26.7%. While overall levels of adiponectin did not differ, individual values changed such that weight loss predicted increases in adiponectin levels. Though initial weight did not predict weight loss, baseline lipid and insulin levels positively predicted weight loss. CONCLUSION: Initial metabolic parameters may be predictors of weight loss. Beneficial effects of weight loss as achieved through diet and exercise on measured parameters indicate moderate weight loss reduces key risk factors of cardiovascular disease in overweight individuals.     

Effect of the Mediterranean diet on plasma adipokine concentrations in men with metabolic syndrome

ObjectiveWhile a Mediterranean dietary pattern (MedDiet) has been associated with favorable changes in several features of metabolic syndrome (MetS), its impact on plasma adipokine concentrations remains largely unknown. The objective of this study was to determine the impact of the MedDiet consumed under controlled feeding conditions, without (? WL) and with weight loss (+ WL), on plasma adipokine concentrations in adult men with MetS (NCEP-ATP III).Materials/MethodsThe diet of 26 men with MetS (age 24 to 62 yrs) was first standardized to a North American control diet for 5 weeks. Participants then consumed a pre-determined MedDiet for 5 weeks. Both diets were consumed under weight-maintaining isoenergetic feeding conditions. Participants then underwent a 20-week free-living caloric restriction period, after which they consumed the MedDiet again in weight stabilizing, isoenergetic feeding conditions.ResultsBody weight was reduced by 10.2% ± 2.9% and waist circumference by 8.6 ± 3.3 cm after the weight loss period and stabilization on MedDiet (P < 0.001). MedDiet ? WL had no impact on plasma concentrations of leptin, plasminogen activator inhibitor-1, resistin, visfatin, acylation stimulating protein and adiponectin. MedDiet + WL reduced plasma leptin concentrations (P < 0.01) and increased plasma adiponectin concentrations (P < 0.05) compared with the control diet and MedDiet ? WL.ConclusionData from this nutritionally controlled study suggest that short-term consumption of MedDiet has little effect on the concentrations of many adipokines in the absence of weight loss.     

Dose-response relationships in 1,3-butanediol-induced potentiation of carbon tetrachloride toxicity

Pretreatment of rats with 1,3-butanediol (BD) (1.0, 5.0, or 10.0% in drinking water) for 7 days enhanced the hepatotoxic, but not the nephrotoxic, effect of a single dose of CCl₄ (0.1 ml/kg, ip) in a dose-related manner. Biochemical tests and light microscopy were employed to assess toxicity. The smallest dosage of BD needed to potentiate CCl₄ hepatotoxicity was estimated to be between 0.1 and 1.0 g/kg/day. The potentiated response appeared to be related to the severity of the metabolic ketosis produced by BD. Pretreatment with BD (10.0%) resulted in increased hepatic microsomal activity and cytochrome P-450 content; the in vitro binding of ¹⁴CCl₄-derived radioactivity to microsomal protein was increased both aerobically and anaerobically, but was greater under aerobic conditions. BD appeared to potentiate CCl₄ liver injury, at least in part, by producing an increase and/or alteration in mixed function activation of CCl₄ to toxic metabolites. Pretreatment with BD (1.0, 10.0%) also resulted in a reduction of hepatic glutathione content. Thus, BD potentiation may arise through several, interrelated pathways.