Clinical evaluation of urinary excretion of liver-type fatty acid-binding protein as a marker for the monitoring of chronic kidney disease: a multicenter trial

To confirm the clinical usefulness of the measurement of urinary liver-type fatty acid-binding protein (L-FABP) in chronic kidney disease (CKD), we carried out a multicenter trial. Clinical markers were measured in patients with nondiabetic CKD (n = 48) every 1 to 2 months for a year. We divided patients retrospectively into progression (n = 32) and nonprogression (n = 16) groups on the basis of the rate of disease progression, then assessed several clinical markers. Initially creatinine clearance (Ccr) was similar in the 2 groups; however, the urinary L-FABP level was significantly higher in the former group than in the latter (111.5 vs 53 microg/g creatinine, P < .001). For the monitoring CKD, we set the cutoff values for urinary L-FABP and urinary protein at 17.4 microg/g creatinine and 1.0 g/g creatinine, respectively. Urinary L-FABP was more sensitive than urinary protein in predicting the progression of CKD (93.8% and 68.8%, respectively). However, urinary protein showed greater specificity than did urinary L-FABP (93.8% and 62.5%, respectively). Over time, the progression of CKD tended to correlate with changes in urinary L-FABP (r = - .32, P < .05), but not in urinary protein (r = .18, not significant). The dynamics of urinary protein differed from that of urinary L-FABP, which increased as Ccr declined. Urinary L-FABP is more sensitive than urinary protein in predicting the progression of CKD. Urinary excretion of L-FABP increases with the deterioration of kidney function. Urinary L-FABP is therefore a useful clinical marker in the monitoring of CKD.     

Test‐retest reliability of effective connectivity in the face perception network

Computational approaches have great potential for moving neuroscience toward mechanistic models of the functional integration among brain regions. Dynamic causal modeling (DCM) offers a promising framework for inferring the effective connectivity among brain regions and thus unraveling the neural mechanisms of both normal cognitive function and psychiatric disorders. While the benefit of such approaches depends heavily on their reliability, systematic analyses of the within‐subject stability are rare. Here, we present a thorough investigation of the test‐retest reliability of an fMRI paradigm for DCM analysis dedicated to unraveling intra‐ and interhemispheric integration among the core regions of the face perception network. First, we examined the reliability of face‐specific BOLD activity in 25 healthy volunteers, who performed a face perception paradigm in two separate sessions. We found good to excellent reliability of BOLD activity within the DCM‐relevant regions. Second, we assessed the stability of effective connectivity among these regions by analyzing the reliability of Bayesian model selection and model parameter estimation in DCM. Reliability was excellent for the negative free energy and good for model parameter estimation, when restricting the analysis to parameters with substantial effect sizes. Third, even when the experiment was shortened, reliability of BOLD activity and DCM results dropped only slightly as a function of the length of the experiment. This suggests that the face perception paradigm presented here provides reliable estimates for both conventional activation and effective connectivity measures. We conclude this paper with an outlook on potential clinical applications of the paradigm for studying psychiatric disorders. Hum Brain Mapp 37:730–744, 2016. © 2015 Wiley Periodicals, Inc.     

解偶联蛋白2与非酒精性脂肪性肝病关系研究进展

目前,非酒精性脂肪肝病(NAFLD)的发病率逐年攀升,已成为危害人类健康的三大肝病之一。解偶联蛋白-2(UCP-2)是新发现的一种位于线粒体内膜上的载体蛋白,具有刺激产热,减少ATP生成,抑制反应性氧簇的产生,负性调节胰岛素分泌以及抗凋亡作用。在脂肪肝中,UCP-2表达增加。现就UCP-2在NAFLD中的作用进行综述。     

Quadro lipidico plasmatico nel diabetico prima e dopo trattamento con insulina: Lipidi totali,trigliceridi, fosfolipidi,colesterolo α- e β-lipoproteico e singoli NEFA (C16-C18)

Riassunto In 24 pazienti, divisi per sesso, affetti da diabete mellito, sono stati determinati, prima e dopo trattamento con insulina, i livelli sierici dei seguenti parametri: acidi palmitico, palmitoleico, stearico, oleico e linoleico, lipidi totali, trigliceridi, fosfolipidi, colesterolo - e -lipoproteico, nonché la composizione percentuale dei singoli NEFA. Si è proceduto ad un confronto statistico dei dati rilevati prima e dopo terapia insulinica e con quelli relativi ad un gruppo di 23 soggetti normali. Nei diabetici prima del trattamento insulinico sono stati riscontrati elevati livelli dei singoli NEFA (tutti altamente significativi rispetto ai normali) e scarsi aumenti dei lipidi totali, del colesterolo totale, del colesterolo -lipoproteico, del rapporto /-lipoproteico; diminuito è risultato il colesterolo -lipoproteico; poco modificati i trigliceridi e i fosfolipidi. Dopo terapia insulinica, si è osservata una generale tendenza verso il ritorno alla norma dei varî parametri, ma i livelli dei singoli NEFA, pur diminuendo, sono rimasti al disopra dei valori normali di circa il 100 %. Viene brevemente discusso questo dato di particolare importanza.

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Summary The serum levels of palmitic, palmitoleic, stearic, oleic and linoleic acids, total lipids, triglycerides, phospholipids, - and -lipoprotein cholesterol and the percentage composition of the NEFA were determined in 24 diabetics divided by sex. A statistical comparison was made of the data before and after insulin treatment and with a group of 23 normals. Before insulin treatment the diabetics presented high levels of the individual NEFA (all highly significant with reference to the normals) and small increases in total lipids, total cholesterol, -lipoprotein cholesterol and /-lipoprotein ratio, a decrease in -lipoprotein cholesterol and hardly any change in triglycerides and phospholipids. Insulin therapy was followed by a general tendency to normalisation of the values but the levels of the individual NEFA, although lower, were nonetheless about 100 % above normal. The importance of this datum is briefly discussed.

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Zusammenfassung Bei 24 Diabetikern wurden vor und nach Insulinbehandlung die folgenden Serumspiegel bestimmt: Palmitinsäure, Palmitölsäure, Ölsäure, Linolsäure, Gesamtlipide, Triglyzeride, Phospholipide, alpha- und beta-Lipoprotein-Cholesterol, sowie die prozentuale Zusammensetzung der verschiedenen NEFA. Die vor und nach Insulinbehandlung erhaltenen Werte wurden untereinander sowohl als auch mit denen von 23 Normalpersonen verglichen. Vor Insulinbehandlung fanden sich bei Diabetikern hohe Spiegel einzelner NEFA (hochsignifikante Unterschiede gegenüber Normalpersonen) und geringe Anstiege der Gesamtlipide, des Gesamtcholesterols und des beta-Lipoprotein-Cholesterol, sowie des beta/alpha-Verhältnisses. Alpha-Liprotein-Cholesterol war vermindert, Triglyzeride und Phospholipide zeigten geringe Veränderungen. Nach Insulinbehandlung zeigte sich eine allgemeine Tendenz zur Normalisierung der verschiedenen Werte, aber die NEFA blieben trotz der beobachteten Verminderung etwa 100 % über den Normalwerten. Diese besonders wichtige Feststellung wird kurz besprochen.

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Resumen En 24 pacientes, subdivididos por sexos, se han determinado antes y después del tratamiento con insulina, los niveles serosos de los siguientes parámetros: ácidos palmítico, palmitoleico, esteárico, oleico, lípidos totales, triglicéridos, fosfolípidos, colesterol - y -lipoproteico, así como también el porcentaje de composición de cada NEFA. Se ha hecho una comparación estadística entre los datos obtenidos antes y después de terapia insulínica y los relativos a un grupo de 23 individuos normales. En los diabéticos antes del tratamiento insulínico se han observado niveles elevados en cada uno de los NEFA (todos altamente significativos respectos a los normales) y escasos aumentos de lípidos totales, del colesterol total, del colesterol -lipoproteico, de la relación /-lipoproteica; en cambio, ha disminuido el colesterol -lipoproteico y han modificado poco los triglicéridos y los fosfolípidos.Tras terapia insulínica se observa una tendencia general hacia la vuelta a la normalidad de los varios parámetros, pero los niveles de cada NEFA, aun disminuyendo, han permanecido el 100 % aproximadamente por encima de los valores normales. Se discute brevemente ese dato que es de particular importancia.

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Résumé Les niveaux sériques des paramètres suivants: acides pamitique, palmitoléique, stéarique, oléique, linoléique, lipides totaux, triglycérides, phospholipides, cholestérol - et -lipoprotéique, ainsi que la composition pourcent des différents NEFA ont été déterminés pour 24 patients, partagés par sexe, avant et après traitement avec insuline. Ensuite, on a procédé à une comparaison statistique des données vérifiées avant et après la thérapie à base d'insuline et avec celles d'un groupes de 23 sujets normaux. Dans les diabétiques, avant le traitement à base d'insuline, on a vérifié des niveaux élevés des différents NEFA (tous très significatifs par rapport aux normaux) et des accroissements réduits des lipides totaux, du cholestérol -lipoprotéique. Peu de changements en ce qui concerne les triglycérides et les phospholipides. Après une thérapie à base d'insuline, on a vérifié une tendance générale vers la normalité des différents paramètres. Cependant, les niveaux des divers NEFA, tout en diminuant, sont restés au-dessus des valeurs normales de 100 % environ. On discute en bref cet élément particulièrement important.

     

Treatment of patients with non-alcoholic fatty liver disease: current views and perspectives.

Non-alcoholic fatty liver disease is considered a component of the metabolic syndrome associated with obesity. Problems still exist concerning non-alcoholic fatty liver disease patients in clinical practice, for example: (a) how to diagnose non-alcoholic fatty liver disease and its type; (b) how to select patients candidate to treatment; (c) how to treat selected patients. Non-alcoholic fatty liver disease includes steatosis and non-alcoholic steatohepatitis, but only non-alcoholic steatohepatitis evolves into cirrhosis and the absolute risk of mortality for non-alcoholic fatty liver disease is low. As yet, no tools, other than liver biopsy, are available to differentiate the various types of non-alcoholic fatty liver disease. Many drugs are, currently, under study to treat non-alcoholic fatty liver disease, even if well-performed trials are until necessary to define the best treatment. At the moment, the entity of the problem and the characteristics of patients frequently put the physician, in clinical practice, to choose the therapeutic approach arbitrarily which is considered more effective for each individual patient. Probably the future will consider the possibility of treating non-alcoholic fatty liver disease with more than one drug, by considering the various aspects and degree of this syndrome. Actually each physician should select the individual treatment on the basis of his/her knowledge and experience, by never forgetting the old saying 'primum non nocere'. However, the epidemiological entity of the problem, the characteristics of the patients, generally young, the frequent lack of clinical evidence of involvement of the liver, are all the factors that require vast well-performed clinical trials in order to define the best therapeutic approach for each individual patient.     

重复性饥饿再投喂对大鼠UCP-2、3表达影响

目的探讨幼鼠和成年大鼠重复性饥饿再投喂饲喂方式处理后,解偶联蛋白(UCPs)mRNA表达变化。方法设计重复性饥饿1 d/再投喂1 d,持续6周的饲喂方式处理幼鼠和成鼠,比较体重、Lee’s指数,检测血糖、游离脂肪酸(FFA)和胆碱酯酶(CHE)含量,白色脂肪组织UCP 2 mRNA和肌肉组织UCP 3 mRNA表达水平。结果饥饿再投喂组幼鼠和成年大鼠体重分别为(243.73±17.66)、(261.12±19.51)g,明显低于对照组幼鼠(375.36±21.12)g和成年大鼠(396±18.14)g(P<0.01);与对照组比较,饥饿再投喂大鼠血清FFA升高(P<0.05),成年大鼠血糖含量降低(P<0.05);分别与幼鼠对照组与饥饿再投喂组大鼠比较,成鼠血清CHE含量明显升高(P<0.01)。与对照组比较,饥饿再投喂组大鼠白色脂肪组织UCP 2 mRNA表达升高(P<0.05);与幼鼠对照组比较,成年对照组大鼠白色脂肪组织UCP 2 mRNA表达降低(P<0.05);与饥饿再投喂幼鼠比较,饥饿再投喂组成年大鼠白色脂肪组织UCP 2 mRNA表达升高(P<0.05)。结论重复性饥饿再投喂处理能使大鼠白色脂肪组织UCP 2 mRNA的表达水平升高,提高大鼠基础能量代谢率。     

渗出型老年性黄斑变性的吲哚青绿血管造影观察

目的观察渗出型老年性黄斑变性(AMD)的吲哚青绿血管造影(ICGA)特征.方法对27例(32只眼)渗出型AMD行ICGA造影或(和)眼底荧光血管造影(FFA)检查,并对二者的造影表现特点和差异进行比较.结果 FFA检查29只眼,诊断典型性CNV11只眼(37.93%),表现为黄斑部早期有网状强荧光性CNV,后期荧光素不断渗漏,并积存在RPE脱离范围之内.晚期形成明显区域性强荧光.诊断隐匿性CNV18只眼(62.07%),表现为早期无CNV特征,晚期有不明原因的边界不清强荧光5只眼(17.24%),而表现早期有边界模糊强荧光呈进行性渗漏,晚期强荧光区明显扩大13只眼(44.82%).ICGA检查32只眼,诊断典型性CNV32只眼(100%),表现为早期有强荧光性CNV性11只眼(34.37%),中期出现强荧光性CNV15只眼(46.88%),晚期又出现新的强荧光性CNV6只眼(18.75%).表明FFA和ICGA在渗出型AMD的CNV的诊断比率上,二者有显著差异.ICGA比FFA能更精确地显示黄斑部的CNV,而对于黄斑部视网膜下出血、浆液性色素上皮脱离等视网膜病变则不如FFA显示明确.结论 ICGA能发现FFA不能发现的CNV,在显示CNV的数量、位置、范围等方面比FFA敏感和准确,是诊断渗出型AMD的CNV和指导其激光光凝的一项重要工具.