Low-density lipoprotein cholesterol level in patients with acute myocardial infarction having percutaneous coronary intervention (the cholesterol paradox)

The relation between low-density lipoprotein (LDL) cholesterol levels and clinical outcomes after percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI) has not been described. A total of 9,571 eligible patients (mean age 62.6 ± 12.5 years, 6,967 men) who underwent PCI with a final diagnosis of AMI from the Korea Acute Myocardial Infarction Registry (KAMIR) were divided into 5 groups according to LDL cholesterol level: < 70, 70 to 99, 100 to 129, 130 to 159, and ≥ 160 mg/dl. Clinical outcomes in hospital and 1 and 12 months after PCI in patients with AMI were examined. Age and co-morbidities decreased as LDL cholesterol increased. Patients with higher LDL cholesterol levels had favorable hemodynamic status and laboratory findings. Lifesaving medications, including lipid-lowering drugs, were underused in patients with lower LDL cholesterol levels. Clinical outcomes in hospital and 1 and 12 months after PCI showed better results as LDL cholesterol increased, except for patients with LDL cholesterol levels ≥ 160 mg/dl. In a Cox proportional-hazards model, LDL cholesterol level was not an independent predictor of mortality at 12 months, after adjusting for clinical characteristics including demographics and biologic data. In conclusion, the cholesterol paradox in patients with AMI is related to confounding by baseline characteristics associated with survival. More intensive treatment including lipid-lowering therapy for AMI in patients with lower LDL cholesterol level may result in better clinical outcomes.     

FcgammaRIIa mediates C-reactive protein-induced inflammatory responses of human vascular smooth muscle cells by activating NADPH oxidase 4

OBJECTIVES: We investigated the mechanism by which C-reactive protein (CRP) affects pro-inflammatory activities of vascular smooth muscle cells (VSMCs). METHODS AND RESULTS: RT-PCR, flow cytometry, and immunoblotting assays consistently showed the expression of FcgammaRIIa by cultured VSMCs isolated from human coronary arteries. Immunofluorescence staining of human coronary artery plaque showed the co-localization of FcgammaRIIa with alpha-actin(+) VSMCs in atheromatous regions. Confocal microscopic image analysis of H(2)DCFDA-labeled cells showed that CRP induced intracellular reactive oxygen species (ROS) generation by FcgammaRIIa(+) HEK293T cells. Moreover, CRP time- and dose-dependently generated ROS in VSMCs through FcgammaRIIa activation. VSMCs mainly express NADPH oxidase 4 isoform (Nox4), the suppression of which using a specific siRNA completely abolished CRP-induced ROS generation by VSMCs. The downregulation of p22(phox), a component of the active Nox4 complex, by transfecting with specific decoy oligomers and functional blocking of FcgammaRIIa not only inhibited the CRP-induced ROS generation but also reduced the degree of AP-1 and NF-kappaB activation, the production of MCP-1, IL-6, and ET-1, and the apoptotic changes of VSMCs in response to CRP. CONCLUSIONS: CRP-induced ROS generation by VSMCs, which requires functional activation of FcgammaRIIa and NADPH oxidase 4, orchestrates pro-inflammatory activities of VSMCs and may eventually promote atherogenesis and plaque rupture.     

Plasticity and memory in the prefrontal cortex

Neuropsychological and neuroimaging studies in humans have shown that the prefrontal cortex (PFC) is involved in long-term memory functioning. In general, the participation of the PFC in long-term memory has been attributed to its role in executive control rather than information storage. Accumulating data from recent animal studies, however, suggest the possible role of the PFC in the storage of long-term memory. In support of this view, there is evidence that various projection systems in the PFC support long-term synaptic plasticity. Recording studies have further demonstrated neural correlates of learning in various animal species. Lastly, behavioral and physiological studies indicate that the PFC is critically involved in memory consolidation, retrieval and extinction processes. These studies then suggest that the PFC is an integral part of the neural network where long-term memory trace is stored and retrieved. Though decisive evidence is still lacking at present, we propose here to assign a term 'control memory' (i.e., memory for top-down control processes) as a new type of memory function for the PFC. This new principle of PFC-long-term memory can help organize existing data and provide novel insights into future empirical studies.     

Effect of soft tissue thickness over the posterior border of the vertebral body and disc space on cage placement during posterior lumbar interbody fusion: A cadaveric study

In the present study, we investigated whether there is a difference between visual depth (VD) and radiological image depth (RD) of cages (i.e., structural interbody support devices) placed in disc spaces during posterior lumbar interbody fusion and whether soft tissues covering the posterior border of the vertebral body and associated disc space are the cause of any observed differences. Using digital calipers, cages were inserted at a depth of 5 mm from the soft tissues covering the posterior border of the vertebral body and disc space under direct vision; this depth was defined as VD. After insertion, RD was measured in triplicate. The reliability of RD measurements was evaluated using an intraclass coefficient test. To identify the cause of differences between VD and RD, the thicknesses of soft tissues were measured microscopically. A total of 40 lumbar intervertebral disc spaces with cages were evaluated. The mean RD of cages was 3.12 mm, while the mean difference between the VD and RD of cages (DVRD) was 1.91 mm. On histological examination, the mean thickness of the soft tissue was 2.02 mm. Comparative analysis between histological values and DVRD showed no statistical difference (P = 1.14, 1.55, 0.06). There was a significant difference between VD and RD during cage placement, and soft tissue structure appeared to be responsible for the DVRD of inserted cages. Therefore, cages should be inserted deeper to account for differences between visual and radiological image depths. Clin. Anat. 25:1066–1073, 2012. © 2012 Wiley Periodicals, Inc.