Assessment of myocardial triglyceride oxidation with PET and 11C-palmitate

Background  The goal of this study was to test whether myocardial triglyceride (TG) turnover including oxidation of TG-derived fatty acids (FA) could be assessed with PET and ¹¹C-palmitate. Methods and Results  A total of 26 dogs were studied fasted (FAST), during Intralipid infusion (IL), during a hyperinsulinemic-euglycemic clamp without (HIEG), or with Intralipid infusion (HIEG + IL). ¹¹C-palmitate was injected, and 45 minutes were allowed for labeling of myocardial TG pool. 3D PET data were then acquired for 60 minutes, with first 15 minutes at baseline followed by 45 minutes during cardiac work stimulated with constant infusion of either phenylephrine (FAST, n = 6; IL, n = 6; HIEG + IL, n = 6) or dobutamine (FAST, n = 4; HIEG, n = 4). Myocardial ¹¹C washout during adrenergic stimulation (AS) was fitted to a mono-exponential function (Km(PET)). To determine the source of this ¹¹C clearance, Km(PET) was compared to direct coronary sinus-arterial measurements of total ¹¹C activity, ¹¹C-palmitate, and ¹¹CO₂. Before AS, PET curves in all groups were flat indicating absence of net clearance of ¹¹C activity from heart. In both FAST groups, AS resulted in negligible net ¹¹C activity and ¹¹CO₂ production higher than net ¹¹C-palmitate uptake. AS with phenylephrine resulted in net myocardial uptake of total ¹¹C activity and ¹¹C-palmitate in IL and HIEG + IL, and ¹¹CO₂ production lower than ¹¹C-palmitate uptake. In contrast, AS with dobutamine in HIEG resulted in net clearance of all ¹¹C metabolites (total ¹¹C activity, ¹¹C-palmitate and ¹¹CO₂) with ¹¹CO₂ contributing 66% to endogenous FA oxidation. The AS resulted in significant Km(PET) in all the groups, except HIEG + IL. However, positive correlation between Km(PET) and ¹¹CO₂ was observed only in HIEG (R ² = 0.83, P = .09). Conclusions  This is the first study to demonstrate that using PET and pre-labeling of intracardiac TG pool with ¹¹C-palmitate, noninvasive assessment of myocardial TG use is feasible under metabolic conditions that favor endogenous TG use such as increased metabolic demand (β-adrenergic stimulation of cardiac work) with limited availability of exogenous substrate (HIEG).     

Time-dependent loss of surface complement regulatory activity during storage of donor blood

The survival of transfused red cells (RBCs) diminishes with time of in vitro storage in blood banks, but the molecular mechanisms underlying the slow but incessant deterioration are incompletely understood. To investigate the possibility that impaired resistance to autologous complement attack could play a role in this phenomenon, packed RBCs stored for variable periods were assayed for decay-accelerating factor (DAF) and CD59, two glycoinositol-phospholipid (GPI)-anchored, membrane- associated complement regulatory proteins that function physiologically to protect blood cells from autologous complement activation on their surfaces. Immunoradiometric and flow cytometric assays employing DAF and CD59 monoclonal antibodies showed that levels of both surface proteins gradually declined over 6 weeks. Digestion analyses with phosphatidylinositol-specific phospholipase C, an enzyme that releases GPI-anchored proteins from cell surfaces, showed that DAF and CD59 molecules with GPI anchors containing unacylated inositol were preferentially lost. These findings suggest: 1) that DAF and CD59 molecules with acylated GPI anchors are more stable in RBC membranes than are molecules with unacylated GPI anchors, and 2) that DAF and CD59 loss may participate with other membrane alterations that occur during in vitro storage in compromising the survival of transfused cells.     

How bilingualism shapes the functional architecture of the brain: A study on executive control in early bilinguals and monolinguals

The existence of a behavioral advantage of bilinguals over monolinguals during executive tasks is controversial. A new approach to this issue is to investigate the effect of bilingualism on neural control when performing these tasks as a window to understand when behavioral differences are produced. Here, we tested if early bilinguals use more language‐related networks than monolinguals while performing a go/no‐go task that includes infrequent no‐go and go trials. The RTs and accuracy in both groups did not differ. An independent component analyses (ICA) revealed, however, that bilinguals used the left fronto‐parietal network and the salience network more than monolinguals while processing go infrequent cues and no‐go cues, respectively. It was noteworthy that the modulation of these networks had opposite correlates with performance in bilinguals and monolinguals, which suggests that between‐group differences were more qualitative than quantitative. Our results suggest that bilinguals may differently develop the involvement of the executive control networks that comprise the left inferior frontal gyrus during cognitive control tasks than monolinguals. Hum Brain Mapp 36:5101–5112, 2015. © 2015 Wiley Periodicals, Inc.     

Presynaptic cannabinoid CB2 receptors modulate [3H]‐Glutamate release at subthalamo‐nigral terminals of the rat

Recent studies suggested the expression of CB2 receptors in neurons of the CNS, however, most of these studies have only explored one aspect of the receptors, i.e., expression of protein, messenger RNA, or functional response, and more complete studies appear to be needed to establish adequately their role in the neuronal function. Electron microscopy studies showed the presence of CB2r in asymmetric terminals of the substantia nigra pars reticulata (SNr), and its mRNA appeared is expressed in the subthalamic nucleus. Here, we explore the expression, source, and functional effects of such receptors by different experimental approaches. Through PCR and immunochemistry, we showed mRNA and protein for CB2rs in slices and primary neuronal cultures from subthalamus. GW833972A, GW405833, and JHW 133, three CB2r agonists dose‐dependent inhibited K⁺‐induced [³H]‐Glutamate release in slices of SNr, and the two antagonist/inverse agonists, JTE‐907 and AM630, but not AM281, a CB1r antagonist, prevented GW833972A effect. Subthalamus lesions with kainic acid prevented GW833972A inhibition on release and decreased CB2r protein in nigral synaptosomes, thus nigral CB2rs originate in subthalamus. Inhibition of [³H]‐Glutamate release was PTX‐ and gallein‐sensitive, suggesting a Gi_βγ‐mediated effect. P/Q Ca²⁺‐type channel blocker, ω‐Agatoxin‐TK, also inhibited the [³H]‐Glutamate release, this effect was occluded with GW833972A inhibition, indicating that the βγ subunit effect is exerted on Ca²⁺channel activity. Finally, microinjections of GW833972A in SNr induced contralateral turning. Our data showed that presynaptic CB2rs inhibit [³H]‐Glutamate release in subthalamo‐nigral terminals by P/Q‐channels modulation through the Gi_βγ subunit and suggested their participation in motor behavior.     

Post‐stroke depression: can we predict its development from the acute stroke phase?

Objectives – To identify possible predictive factors for post‐stroke depression (PSD) in the acute phase of stroke. Methods – The study design was prospective, observational cohort study of patients with acute cerebral infarction (CI). Neurological and neuropsychological evaluations were conducted within the first 10 days from the onset of stroke and repeated at the 3‐month follow‐up. DSM‐IV criteria were used to define PSD. Results – From a total of 85 patients with CI, 59 patients completed the 3‐month follow‐up and 17 of them (28.8 %) fulfilled PSD criteria at the 3‐month follow‐up. Melancholy index of the Hamilton Depression Rankin Scale (HDRS) was associated with a risk three times greater than that of PSD at the 3‐month follow‐up in the univariate analysis (OR 3.07; 95% CI 1.53–6.16; P = 0.002) with no significant influence of stroke severity or the location of brain infarction (right or left side). The receiver operating characteristic curves pointed to a melancholy index ≥1.5 as the optimal cut‐off level associated with the development of PSD at the 3‐month follow‐up. Conclusions – Melancholy index of the HDRS ≥1.5 could be a useful clinical tool to detect patients with acute stroke at high risk of developing PSD.     

误诊为脂溢性皮炎的艾滋病2例

例1男,46岁,3年前在当地血站献血数次,筛查HIV抗体未见异常,发病1年前曾与4位女性有婚外性生活史。例2女,51岁,发病15年前有输血史,3年前被确诊为"尖锐湿疣"。该两例患者均表现为泛发红斑鳞屑性皮损,长时间以"脂溢性皮炎"予相应治疗,无好转。血清HIV确证试验均(+)。诊断:艾滋病。经抗反转录病毒药物治疗后脂溢性皮炎样临床表现消失。