Activation of mGlu3 Receptors Stimulates the Production of GDNF in Striatal Neurons

Metabotropic glutamate (mGlu) receptors have been considered potential targets for the therapy of experimental parkinsonism. One hypothetical advantage associated with the use of mGlu receptor ligands is the lack of the adverse effects typically induced by ionotropic glutamate receptor antagonists, such as sedation, ataxia, and severe learning impairment. Low doses of the mGlu2/3 metabotropic glutamate receptor agonist, LY379268 (0.25–3 mg/kg, i.p.) increased glial cell line-derived neurotrophic factor (GDNF) mRNA and protein levels in the mouse brain, as assessed by in situ hybridization, real-time PCR, immunoblotting, and immunohistochemistry. This increase was prominent in the striatum, but was also observed in the cerebral cortex. GDNF mRNA levels peaked at 3 h and declined afterwards, whereas GDNF protein levels progressively increased from 24 to 72 h following LY379268 injection. The action of LY379268 was abrogated by the mGlu2/3 receptor antagonist, LY341495 (1 mg/kg, i.p.), and was lost in mGlu3 receptor knockout mice, but not in mGlu2 receptor knockout mice. In pure cultures of striatal neurons, the increase in GDNF induced by LY379268 required the activation of the mitogen-activated protein kinase and phosphatidylinositol-3-kinase pathways, as shown by the use of specific inhibitors of the two pathways. Both in vivo and in vitro studies led to the conclusion that neurons were the only source of GDNF in response to mGlu3 receptor activation. Remarkably, acute or repeated injections of LY379268 at doses that enhanced striatal GDNF levels (0.25 or 3 mg/kg, i.p.) were highly protective against nigro-striatal damage induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in mice, as assessed by stereological counting of tyrosine hydroxylase-positive neurons in the pars compacta of the substantia nigra. We speculate that selective mGlu3 receptor agonists or enhancers are potential candidates as neuroprotective agents in Parkinson's disease, and their use might circumvent the limitations associated with the administration of exogenous GDNF

Influence of Risk Factors on Coronary Flow Reserve in Patients with 1-Vessel Coronary Artery Disease.

Coronary artery disease (CAD) risk factors influence the hyperemic response in patients without coronary artery stenosis. The aim of this study was to evaluate the influence of risk factors on coronary flow reserve (CFR) estimated by 99mTc-sestamibi cardiac imaging in patients with 1-vessel CAD. Methods: Fortyeight patients with 1-vessel CAD were enrolled in the study. Systemic hypertension, hypercholesterolemia, diabetes mellitus, and cigarette smoking were considered CAD risk factors. Within 48 h, all patients underwent coronary angiography and regional CFR assessment by 99mTc-sestamibi imaging with dipyridamole (0.74 mg/kg of body weight). Eight patients had no risk factors, 14 had 1 risk factor, 18 had 2 risk factors, and 8 had 3 risk factors. Results: The mean CFR of the narrowed coronary vessel was 1.28 +/- 0.43 in the overall study population (1.52 +/- 0.30 in patients with 50%–70% stenosis and 0.94 0.75 in patients with 70% stenosis; P < 0.001). Two-factor ANOVA showed that the number of risk factors significantly affected CFR (P < 0.001) in patients with 50%–70% stenosis, whereas significance was only borderline in patients with >70% stenosis. Finally, a significant interaction among the degree of coronary artery stenosis, the number of risk factors, and the estimated CFR was found. Conclusion: CFR is inversely related to the number of conventional risk factors in patients with 1-vessel CAD and intermediate coronary artery stenosis, whereas this influence is less evident in patients with more severe stenosis

Estimation of coronary flow reserve by Tc-99m sestamibi imaging in patients with coronary artery disease: comparison with the results of intracoronary Doppler technique

BACKGROUND: This study compared coronary flow reserve (CFR) estimated by technetium 99m sestamibi imaging with the results obtained with intracoronary Doppler in patients with coronary artery disease. Intraobserver and nterobserver reproducibility of the radionuclide-estimated CFR was also assessed. METHODS AND RESULTS: Fourteen consecutive patients (mean age, 54 +/- 7 years) with documented coronary artery disease in whom percutaneous coronary intervention was planned underwent dipyridamole (0.74 mg/kg) sestamibi imaging and intracoronary Doppler within 5 days. Myocardial blood flow (MBF) was estimated by measurement of first transit counts in the pulmonary artery and myocardial counts from single photon emission computed tomography images. Estimated CFR was expressed as the ratio of stress MBF to rest MBF. In the study vessels, CFR was 1.36 +/- 0.43 as estimated by sestamibi and 1.39 +/- 0.42 by intracoronary Doppler ( P = .69). A significant relationship between CFR estimated by sestamibi and CFR obtained by intracoronary Doppler was observed ( r= 0.85, P < .001). On Bland-Altman analysis, the mean difference between CFR by sestamibi and by Doppler was 0.03 and the intraclass correlation coefficients for intraobserver and interobserver reproducibility were high (all P < .001) for both global and regional CFR. CONCLUSIONS: This study demonstrates a good agreement between CFR estimated by sestamibi imaging and by intracoronary Doppler results and a lack of intraobserver and interobserver variability of this noninvasive approach

Automated volumetry of pulmonary nodules on multidetector ct: influence of slice thickness, reconstruction algorithm and tube currente. Preliminary results.

To evaluate the influence of slice thickness, reconstruction algorithm and tube current (mA) on the performance of a software package in determining the volume of solid pulmonary nodules on multidetector-row computed tomography (MDCT). MATERIALS AND METHODS: A chest phantom containing artificial solid nodules with known volume was imaged with two MDCT scans at 100 and 40 mAs (200 mA and 80 mA, 0.5-s rotation time), respectively. Data were reconstructed with slice thicknesses of 1.25 and 2.5 mm and five different algorithms. The volumes of three nodules (juxtavascular, intraparenchymal, juxtapleural) were calculated using three-dimensional (3D) volumetric software. Differences between estimated and real volume were reported for each nodule and reconstruction set. RESULTS: The software segmented all nodules on 1.25-mm-thick reconstructions, independently from the mAs. It did not segment the juxtapleural nodule on 2.5-mm-thick reconstructions at 40 mAs. Mean values of the differences, which better approximated the real volume of the nodules, were obtained with high-spatial-resolution algorithms on both 100 and 40 mAs images at 1.25-mm slice thickness. CONCLUSIONS: Slice thickness, reconstruction algorithm and tube current can affect the 3D volume measurement of solid nodules. The best performance of the software, on both 100 and 40 mAs images, was observed with a slice thickness of 1.25 mm and high-spatial-resolution algorithms

Diagnosis and management of hemoptysis

Hemoptysis is the expectoration of blood that originates from the lower respiratory tract. It is usually a self-limiting event but in fewer than 5% of cases it may be massive, representing a life-threatening condition that warrants urgent investigations and treatment. This article aims to provide a comprehensive literature review on hemoptysis, analyzing its causes and pathophysiologic mechanisms, and providing details about anatomy and imaging of systemic bronchial and nonbronchial arteries responsible for hemoptysis. Strengths and limits of chest radiography, bronchoscopy, multidetector computed tomography (MDCT), MDCT angiography and digital subtraction angiography to assess the cause and lead the treatment of hemoptysis were reported, with particular emphasis on MDCT angiography. Treatment options for recurrent or massive hemoptysis were summarized, highlighting the predominant role of bronchial artery embolization. Finally, a guide was proposed for managing massive and nonmassive hemoptysis, according to the most recent medical literature