Background-The proinflammatory prostaglandin E 2 (PGE 2 ) fluctuates over time in the cerebrospinal fluid of patients with Alzheimer's disease (AD), but the cerebral distribution and expression patterns of microsomal prostaglandin-E synthase (mPGES)-1 have not been compared with those of normal human brains.

Nonsteroidal anti-inflammatory drugs, such as cyclooxygenase (COX)-2 inhibitors, have been unsuccessful in slowing or reversing Alzheimer’s disease (AD). Thus, understanding the expression patterns of the downstream effectors for the regulation of prostaglandin synthesis may be important for understanding the pathological processes involved in AD and formulating more effective pharmacotherapeutics for this disease. In this study, we used immunofluorescence, immunohistochemistry, and Western blot analysis to compare patterns of microsomal prostaglandin E synthase (mPGES)-2 expression in the middle frontal gyrus (MFG) of AD patients and age-matched controls. In control human brain sections, mPGES-2 immunoreactivity was observed in neurons, activated microglia, and endothelium, but not in resting microglia, astrocytes, or smooth muscle cells. Microsomal PGES-2 immunoreactivity was particularly elevated in the pyramidal neurons of brains from three of five sporadic and four of five familial AD patients compared with four of five age-matched control brains that showed minimal immunoreactivity. In contrast, Western blot analysis revealed no difference in mPGES-2 levels between end-stage AD brain tissue and control brain tissue. These results suggest that in human cortex, mPGES-2 is constitutive in neurons and endothelium and induced in activated microglia. Furthermore, the high immunoreactivity of mPGES-2 in pyramidal neurons of AD brains indicates that it might have a potential role in the functional replacement of cytosolic PGES or inactive mPGES-1 in later stages of AD.

In CRT treatment outside of the clinical trial setting, CRT-D treatment was not an independent predictor of long-term survival. Future research should focus on correct selection of the patients who receive enough benefit of an added defibrillator to justify CRT-D implantation instead of CRT-P treatment only.

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Background Late gadolinium enhancement (LGE) border zone on cardiac-MRI (CMR) has been proposed as an independent predictor of ventricular arrhythmias. The purpose was to determine if size and heterogeneity of LGE predict appropriate implantable cardioverter defibrillator (ICD) therapy in ischemic cardiomyopathy (ICM) and non-ischemic cardiomyopathy (NICM) patients and evaluate four LGE border zone algorithms. Methods and Results ICM and NICM patients who underwent LGE-CMR prior to ICD implantation were retrospectively included. Two semi-automatic algorithms, EWA (Expectation Maximization, weighted intensity, a priori information) and a weighted border zone algorithm (WBZ) were compared to a modified full-width half-maximum (mFWHM) and a 2–3SD threshold-based algorithm (2–3SD). Hazard ratios (HR) were calculated per 1% increase in LGE. A total of 74 ICM and 34 NICM were followed for 63 months [1–140] and 52 months [0–133] respectively. ICM patients had 27 appropriate ICD-events and NICM patients had seven ICD-events. In ICM patients with primary prophylactic ICD, LGE border zone predicted ICD-therapy in univariable and multivariable analysis measured by the EWA, WBZ and mFWHM algorithms (HR 1.23, 1.22 and 1.05 respectively, P<0.05, negative predictive value 92%). For NICM, total LGE by all four methods was the strongest predictor (HR 1.03–1.04, P<0.05), though the number of events was small. Conclusions Appropriate ICD-therapy can be predicted in ICM patients with primary prevention ICD by quantifying the LGE border zone. In NICM patients, total LGE but not LGE border zone had predictive value for ICD therapy. However, the algorithms used affects the predictive value of these measures.

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Anti-inflammatory drugs reduce the risk of Alzheimer's disease but fail to slow its progression. Studying the expression of prostaglandin E 2 synthases downstream of cyclooxygenase-2 is important. Here, the expression patterns of cytosolic prostaglandin E 2 synthases, an immediate prostaglandin E 2 source was investigated. Sections taken from the middle frontal gyrus of brains of 10 patients with Alzheimer's and 5 age-matched controls were examined by immunostaining for the presence of the synthases. Immunofluorescence analysis of control brains showed that cytosolic prostaglandin E 2 synthases co-localize with microglia, neurons, and endothelium markers, but not with astrocytes or smooth muscle cells. Immunohistochemical staining for the synthases was positive in the pyramidal neurons of controls but barely detectable in the brain of Alzheimer's patients. These findings revealed that cytosolic prostaglandin E 2 synthases is found in microglia, neurons, and endothelium of control human middle frontal gyrus and that its levels decrease in pyramidal cells of Alzheimer's disease brains.