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Background: Because of persistent stunning, post-treatment functional abnormalities could identify the initial risk area. The study aims to detect myocardial salvage using post-revascularization gated SPECT in acute myocardial infarction (AMI) treated by reperfusion therapy. Methods: In 36 AMI patients, we performed a first gated SPECT injecting Tc-sestamibi before primary percutaneous coronary intervention (PCI), and a second 5 days later. The salvage index defined by the two perfusion images was compared with the value obtained by subtracting in the second gated SPECT the extent of perfusion defect from the extent of wall thickening abnormalities. Results: The wall thickening salvage index correlated with the reference perfusion salvage index (Spearman's ρ = .92, P < .0001), with a 95% limit of agreement = ±.25. The agreement between the classifications in salvage index tertiles of the reference and of the wall thickening salvage index was good (kappa = .75). All patients with optimal PCI result and 18/24 of those with intermediate or poor outcome were correctly classified. Conclusions: Comparing function and perfusion in a single post-PCI Tc-sestamibi gated SPECT it is possible to estimate myocardial salvage. This could have useful implications in studies comparing different treatment strategies for AMI. [ABSTRACT FROM AUTHOR]

Female sex and advanced age have adverse prognostic meaning in acute myocardial infarction. Whether gender and/or age influence the relationship between infarct size, infarct severity, and left ventricular ejection fraction (LVEF) is unclear. We examined 460 patients (359 men) with acute myocardial infarction submitted to successful primary percutaneous coronary intervention. Infarct size, infarct severity, and LVEF were evaluated with perfusion gated SPECT at one month of index infarction. There were no significant correlations between age and infarct size or infarct severity, and between age and LVEF. Moreover, elderly age (≥75 years) did not influence the relationship between LVEF and infarct size or infarct severity. Conversely, there was a significant gender-related difference in the relationship between LVEF and infarct size ( F = 20.5, P < .00001), and between LVEF and infarct severity ( F = 8.6, P < .005). In practice, there was a steeper decrease in LVEF in case of moderate to large infarct size in women than in men. With increasing infarct size, LVEF decreases more sharply in women than in men. Conversely, age does not influence the relationship between infarct dimensions and LVEF. [ABSTRACT FROM AUTHOR]

Background: Atrial fibrillation (AF) and coronary microvascular dysfunction (CMD) are common in hypertrophic cardiomyopathy (HCM), but whether they are associated is unclear. We assessed the relationship between AF and CMD in HCM. Methods and Results: Global hyperemic myocardial blood flow (hMBF) was measured in 95 HCM patients (16 with, 79 without paroxysmal or chronic AF) by N-13 ammonia positron emission tomography (PET) after dipyridamole infusion. AF patients were older (50.5 ± 13.4 vs. 38.7 ± 14.9 years, P < .0005), had larger left atrial diameter (49.8 ± 7.4 vs 38.6 ± 5.7 mm, P < .00001), and left ventricular end-systolic diameter (30.4 ± 6.7 vs 25.5 ± 5.3 mm, P < .005) compared with those in stable sinus rhythm. In patients with AF, hMBF was significantly lower (1.23 ± 0.44 vs 1.87 ± 0.90 mL/min/g, P < 0.0001). In multivariate logistic regression analysis, hMBF, left atrial diameter, and age were independently associated with AF ( P < .05 for all). Conclusions: HCM patients with paroxysmal or chronic AF have lower hMBF than those in stable sinus rhythm. The association between CMD and AF is independent of other known predictors of AF, suggesting a causal link between these two features. [ABSTRACT FROM AUTHOR]

Background: The relationship among plasma brain natriuretic peptide (BNP), markers of extracellular matrix (ECM) remodeling, and left ventricular (LV) dilation after reperfused acute myocardial infarction is poorly known. Methods and Results: Echocardiogram, plasma BNP, and ECM degradation markers (serum amino-terminal telopeptide of type I procollagen and type III procollagen and carboxy-terminal telopeptide of type I procollagen [ICTP]) were evaluated in 34 patients at days 1, 3, and 30 after first reperfused acute myocardial infarction. At 1 month, infarct size and severity and LV volume were measured by sestamibi gated single photon emission computed tomography. Patients were stratified according to day 3 BNP levels into 2 groups: group 1 (n = 17) had BNP values over the median value, and group 2 (n = 17) had BNP values under the median value. Infarct size and severity were similar in the 2 groups. LV volumes increased in group 1 but decreased in group 2 (P < .01). BNP values, LV volume/mass index, and infarct size were independent predictors of 1-month LV dilation (β = .58 [P = .001], β = .41 [P = .01], and β = .32 [P = .03], respectively). Levels of serum amino-terminal propeptide of type I procollagen and type III procollagen were similar in both groups. The level of ICTP increased significantly in group 1 only, and after 3 days, it was higher (P < .01) than in group 2. In group 1 ICTP significantly interacted with the relationship between BNP release and serial changes in LV volumes (F = 4.87, P = .03). Conclusions: ICTP is related to elevated BNP level independently of infarct size and severity and interacts with the relationship between BNP and LV dilation. BNP levels could play a role in LV remodeling by favoring ECM degradation. [Copyright &y& Elsevier]

Background: Gated single photon emission computed tomography (SPECT) identifies functional changes produced by ischemia, but the influence of acquisition delay on their detection is not established. Methods and Results: In 80 patients with known or suspected coronary artery disease, gated SPECT was acquired twice: first, less than 30 minutes after peak exercise (stress 1), and second, more than 45 minutes after peak exercise (stress 2). End-diastolic volume (EDV), end-systolic volume (ESV), and ejection fraction (EF) were compared with perfusion. The relationship between the ΔEF (stress EF − resting EF) and the summed difference score (SDS) was −0.443 (P < .0001) for stress 1 and −0.416 (P < .0001) for stress 2. In stress 1, EF increased in patients without inducible ischemia (SDS = 0) (57% ± 10% vs 54% ± 9% at rest, P < .02) and decreased in those with an SDS of 1 or greater (53% ± 10.8% vs 55% ± 9.6% at rest, P < .05). In stress 2, EF was unchanged in patients without ischemia (55.8% ± 9.7%, P = .06) and decreased in the other patients (52.8% ± 10.2%, P < .01). In patients without ischemia, both the EDV and ESV decreased significantly in stress 1 and were unchanged in stress 2. In patients with an SDS of 1 or greater, the EDV remained unchanged and the ESV minimally decreased in stress 1, whereas both volumes clearly and significantly increased in stress 2. Conclusions: The early acquisition of postexercise gated SPECT is slightly more effective in detecting ischemia-related functional changes; however, a delayed acquisition within 60 minutes still permits the detection of functional abnormalities in most patients. [Copyright &y& Elsevier]

Maladaptive Daydreaming (MD) is an excessive absorption in vivid fantasies interfering with individuals' daily functioning, which has been associated with adverse psychological outcomes and adult attachment insecurities. However, no study to date has addressed the relationships between MD, parental care, unresolved attachment, and psychological symptoms (depression/anxiety and obsessive-compulsive disorder; OCD) in a sample of young adults. In this study, 1295 young adults (401 males) completed an online survey including the Parental Bonding Instrument, Maladaptive Daydreaming Scale, Adult Unresolved Attachment Questionnaire, and the DSM-5 Level 1 Cross-Cutting Symptom Measure. The results evidenced the differential contribution of maternal and paternal care on individuals' psychological symptoms; whilst higher maternal care was negatively related to OCD symptoms, higher paternal care was negatively linked to depression/anxiety symptoms. A relationship between unresolved attachment, MD and psychopathological symptoms emerged; specifically, MD mediated the relationships between unresolved attachment and depression/anxiety and OCD symptoms. Overall, paternal and maternal care may have distinct roles in predicting individuals' psychopathological outcomes. In the presence of unresolved attachment, MD may represent a dissociative response that allows individuals to deal with negative experiences through psychopathological symptoms. Understanding the specific pathways that lead to different psychopathological outcomes could have important implications in developing preventive clinical interventions. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the impact of a clopidogrel therapy on the effectiveness of myocardial reperfusion in patients with ST-segment elevation acute myocardial infarction (AMI) undergoing routine infarct-related artery (IRA) stent implantation and receiving routine abciximab therapy. Background: Inflammatory processes after mechanical restoration of flow in AMI play a central role in decreasing the effectiveness of reperfusion at microcirculatory level. Several studies suggest that clopidogrel may exert a protective effect against adverse cardiovascular events by virtue of its anti-inflammatory properties. Methods: A total of 133 patients with a first ST-elevation AMI were randomized to clopidogrel (600-mg loading dose before IRA stenting followed by 75 mg daily, n = 66) or ticlopidine (500 mg before IRA stenting followed by 250 mg twice daily, n = 67). The primary end point was scintigraphic infarct size at 1 month. The secondary end points were ST-segment elevation resolution within 3 hours of procedure and 1-month clinical outcome, as a composite of death, reinfarction, target vessel revascularization, and stroke within 1 month of the index procedure. Results: The 1-month technetium 99m sestamibi scintigraphy revealed similar infarct size (16.2% +/- 14.6% vs 15.0% +/- 14.1%, P = .703) and severity (0.48 +/- 0.18 vs 0.49 +/- 0.15, P = .592) in the clopidogrel group as compared with the ticlopidine group. Three-hour ST-segment resolution rate was similar in the 2 study groups (86% vs 89%, P = .642). At 1 month, there was no difference in major cardiovascular adverse event rate (3% vs 3%, P = .988). Discontinuation of thienopiridine therapy within the first month occurred in no patient randomized to clopidogrel and in 3 (4.5%) patients randomized to ticlopidine (P = .082). Conclusion: Clopidogrel has no impact on the effectiveness of myocardial reperfusion in patients with AMI treated routinely with stenting and abciximab. However, clopidogrel, administered as a 600-mg loading dose followed by 75 mg daily, is safe and at least as effective as the standard ticlopidine therapy in this subgroup of patients. [ABSTRACT FROM AUTHOR]

Taking advantage of the structural similarity between aspartic proteases, small-molecule peptidomimetic inhibitors that already showed activity towards Secreted Aspartic Protease 2 as anti-Candida agents and HIV protease inhibitors were exploited as potential BACE1 inhibitors. A focused library of 6,8-dioxa-3-azabicyclo[3.2.1]-octane peptidomimetic scaffolds was synthesized and assayed towards BACE1 enzyme, resulting in the identification of a thiolactam-containing hit compound possessing IC 50 in the low micromolar range, and confirming the bicyclic acetal portion as a potential transition state analogue in the interaction with catalytic aspartic acid residues. [ABSTRACT FROM AUTHOR]

Taking advantage of click chemistry, we synthesized triazole-containing RGD peptidomimetics capable of binding to α v β 3 integrin with diverse potency, and selected 125 I-labeled compounds proved to interact in vitro and in vivo with α v β 3 integrin expressed by melanoma cells. Two 125 I-compounds containing either 2-aminobenzimidazole or 2-aminopyridine groups as the arginine bioisostere with the capacity to selectively bind cells of highly expressing α v β 3 melanoma xenografts were found using micro-SPECT imaging studies. [ABSTRACT FROM AUTHOR]

Abstract: Two c[RGDfX] cyclopeptides, having either l- or d-morpholine-3-COOH (Mor) as the X amino acid were developed as ligands for αvβ3/αvβ5 integrins. Biological assays showed only d-Mor-containing cyclopentapeptide capable to bind αvβ3 integrin with a low nanomolar affinity according to a two-site model, thus revealing a connection between the configuration of Mor and the preferred binding to αvβ3 integrin. Conformational analysis showed different structural preferences for the two peptides induced by the two enantiomeric cyclic amino acids, suggesting a role of the stereochemistry of Mor on the overall peptide conformation and on the presentation of the pharmacophoric Arg and Asp side chains. [Copyright &y& Elsevier]

Abstract: CNS diseases such as Parkinson, schizophrenia, and attention deficit hyperactivity disorder (ADHD) are characterized by a significant alteration of dopamine transporter (DAT) density. Thus, the development of compounds that are able to selectively interact with DAT is of great interest. Herein we describe the design and synthesis of a new set of 3-aza-6,8-dioxabicyclo[3.2.1]octanes having a tropane-like structure with additional heteroatoms at positions 3 and 6. The compounds were evaluated for their in vitro receptor binding properties toward human dopamine (hDAT) and serotonin (hSERT) transporters using [3H]WIN35,428 and [3H]citalopram as specific radioligands, respectively. Biological assays revealed that some compounds having the N-3 atom substituted with aryl groups possess significant affinity and selectivity for monoamine transporters, and in particular, compound 5d displayed an IC50 of 21nM toward DAT, and a good selectivity toward SERT (IC50 =1042nM). These results suggest that 3-aryl-3-aza-6,8-dioxabicyclo[3.2.1]octanes may represent a new class of DAT ligands. [Copyright &y& Elsevier]

ST-segment resolution is used to classify the response to reperfusion therapy in acute myocardial infarction, but the possibility to predict outcome in individual patients is unclear, particularly in the setting of primary percutaneous coronary intervention (PCI) and abciximab therapy. We studied 213 patients who underwent successful revascularization with PCI. Maximal ST-segment elevation was measured before and 30 minutes after PCI. Patient outcome was defined on the basis of infarct size and left ventricular ejection fraction (EF) as derived from gated single-photon emission computed tomography that was acquired 1 month after infarction. Patients who had ≥50% ST resolution showed a smaller infarct (15.1 ± 13.6% vs 19.9 ± 15.7%, p <0.05) but not a higher left ventricular EF (48.7 ± 12.3% vs 45.2 ± 11.8%) than did patients who had <50% resolution. According to cluster analysis of infarct size and left ventricular EF, 132 patients had favorable outcome (central values: infarct size 7.5%, left ventricular EF 55%) and 81 did not (central values: infarct size 30%, left ventricular EF 36%). Using receiver-operating characteristic curve analysis, the optimal ST-resolution cutoff was >60%, with 77% sensitivity and 51% specificity for predicting favorable outcome. ST-segment elevation ≤4.5 mV before PCI was 80% sensitive and 48% specific, and ST-segment elevation ≤1 mV after PCI was 74% sensitive and 60% specific for predicting favorable outcome. In conclusion, in the setting of primary PCI and abciximab therapy, ST-segment elevation resolution requires a high threshold (>60%) to effectively classify patients; the capability of ST-segment analysis to predict patient outcome is limited, with ST-segment elevation after PCI showing the best compromise between sensitivity and specificity. [Copyright &y& Elsevier]

Previous positron emission tomography (PET) studies with fluorodeoxglucose (FDG) as tracer in healthy elders showed that the epsilon4 allele of the apolipoprotein E (ApoE) gene is disruptive to cerebral glucose metabolism (rCMRglu), possibly through the interaction with the aging process. The present study was aimed at assessing whether this interaction occurs in patients with Alzheimer''s disease (AD). Eight-six AD patients, including 40 ApoE4 carriers and 46 non-carriers, underwent 18F-FDG PET scanning at rest. ApoE groups were comparable for age, gender, age at onset and disease duration. SPM''99 was used to assess rCMRGlu correlations with age, differences between ApoE groups and ApoE by age interaction, correcting for disease severity. Results were reported at P<0.001, uncorrected. Correlations between age and rCMRGlu confirmed the well-known negative relationship for both groups. Lower rCMRGlu was found within the frontal and cingulate areas for ApoE4 carriers as compared with the non-carriers. Additionally, a significant ApoE by age interaction was detected in the frontal and anterior cingulate cortex, with the ApoE4 carriers having a steeper regression slope with respect to the non-carriers. These results indicate that age-related regional rCMRglu decreases within the frontal and anterior cingulate areas may be more severe in AD patients carrying the ApoE4 allele. [Copyright &y& Elsevier]

Background: The recent introduction of acetylcholinesterase inhibitors (AChEIs) therapy for Alzheimer''s Disease (AD) has led to the need to assess the brain''s response to the therapy on an objective, neurophysiological basis. Brain perfusion single photon emission computed tomography (SPECT) was used in an open-label study to evaluate the effect of chronic Donepezil administration to a group of patients affected by mild to moderate AD, compared to a group of AD patients not receiving AChEIs and kept under observation for a similar period.Methods: Twenty-five consecutive patients with probable AD (National Institute of Neurological and Communicative Disorders and Stroke–Alzheimer’s Disease and Related Disorders Association criteria) (19 women, 6 men; mean age: 74.2±7.2; mean Mini-Mental State Examination score, MMSE: 19.8±3.5) underwent (t0) brain SPECT with 99mTc-hexamethylpropylene-amine-oxime by a brain-dedicated, high-resolution camera and were re-evaluated (t1) after 11±2.6 months of chronic Donepezil administration (5 mg/day) (treated group). Thirteen AD patients (9 women, 4 men, mean age: 71.4±5.7, MMSE score: 20.6±3.5) were not treated with AChEIs and served as controls (untreated group). They were subjected to the same evaluation after 13±1.4 months as the treated group. Statistical parametric mapping (SPM) was employed to analyse SPECT findings.Results: The MMSE score declined significantly (P<0.01) from t0 to t1 both in untreated (from 20.6±3.5 to 17.8±4.4) and in treated (from 19.8±3.5 to 17.8±4.1) group. At t0, the untreated group showed higher regional cerebral blood flow (rCBF) than the treated group in a frontal and a frontal-parietal region of the left hemisphere. Between t0 and t1, significant rCBF reduction was observed in the temporal lobe and occipital-temporal cortex of the left hemisphere in the untreated group, whereas no significant change was observed in the treated group. The rCBF of the two groups did not significantly differ at t1. By covariate SPM analysis between t0 and t1 in treated patients, MMSE score changes correlated significantly with rCBF changes in a large left frontal-temporal region.Conclusions: Brain perfusion is preserved in AD patients undergoing chronic Donepezil therapy while it is reduced in untreated patients. SPECT is a promising tool with which to assess the impact of AChEI therapy on brain functioning of AD patients. [ABSTRACT FROM AUTHOR]

A main goal of revascularization in patients with chronic ischemic cardiomyopathy is to improve global left ventricular (LV) function. This study aimed to verify whether it is possible to predict an increase in LV ejection fraction (EF) after revascularization on the basis of the extent of LV asynergy, myocardial viability, and revascularization completeness. We studied 77 patients with chronic LV ischemic dysfunction using baseline resting and nitrate-enhanced technetium-99m sestamibi single-photon emission computed tomography. Regional wall motion and global LVEF were assessed with echocardiography before and after revascularization, which was complete in 51 patients and incomplete in 26. The number of viable asynergic segments included in revascularized coronary artery territories was the strongest predictor of significant (≥5 EF U) functional improvement in univariate discriminant analysis. According to multivariate stepwise discriminant analysis, this parameter, together with the number of baseline asynergic segments, allowed the detection of patients with significant LVEF improvement with 75% accuracy. With use of a multivariate regression model, including the 2 mentioned variables, the measure of postrevascularization LVEF increase could be accurately quantified (R2 0.43, p <0.000001). In conclusion, this study suggests that the severity of baseline asynergy, the extent of myocardial viability, and the completeness of revascularization are the main determinants of postrevascularization functional recovery in patients with LV ischemic dysfunction, and that on the basis of these variables it is possible to predict the measure of LVEF increase. [Copyright &y& Elsevier]

Abstract: Damage to nonmotor dopamine (DA)-mediated frontostriatal circuits has been proposed as the main pathophysiological basis of cognitive dysfunction in Parkinson''s disease (PD). In the present study, 18 early nondemented drug naive PD patients were investigated, by dual-tracer N-ω-fluoropropyl-2β-carbomethoxy-3β-4-[123I]iodophenyl-nortropane ([123I]FP-CIT) single-photon emission computed tomography (SPECT)/[18F] fluoro-deoxyglucose (FDG) positron emission tomography (PET) imaging, to test whether an early and not yet treatment-modulated relation exists between cognitive functions, caudate nucleus (CN) DA impairment and brain metabolism (CMRglc) in associative frontostriatal circuits. Verbal fluency performance correlated with DA impairment in CN, and with CMRglc in dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC). Further, CMRglc in orbitofrontal cortex, DLPFC, and ACC was shown to be early modulated by the level of DA impairment in CN. The present study demonstrates in vivo the early functional disruption of nonmotor frontostriatal circuits in PD. The effect of CN DA impairment on DLPFC and ACC metabolism is proposed as a possible early pathophysiological and functional substrate for executive dysfunction in PD. [Copyright &y& Elsevier]

Abstract: Having a parent affected with late-onset Alzheimer''s disease (LOAD) is a major risk factor for developing the disease among cognitively normal (NL) individuals. This magnetic resonance imaging (MRI) study examines whether NL with a LOAD-affected parent show preclinical brain atrophy, and whether there are parent-of-origin effects. Voxel-based morphometry (VBM) on Statistical parametric mapping (SPM8) was used to examine volumetric T1-MRI scans of 60 late-middle-aged NL subjects, divided into 3 size-matched, demographically balanced groups of 20 subjects each, including NL with a maternal (FHm), paternal (FHp), or negative family history (FH−) of LOAD. There were no group differences for clinical and neuropsychological measures, and ApoE status. On VBM, FHm showed reduced gray matter volumes (GMV) in frontal, parietal, and temporal cortices and precuneus as compared with FH−, and in precuneus compared with FHp (p < 0.05, family-wise error [FWE]-corrected). Results remained significant controlling for age, gender, education, ApoE, and total intracranial volume. No differences were observed between FHp and FH− in any regions. NL FHm showed reduced GMV in LOAD-affected brain regions compared with FH− and FHp, indicating higher risk for Alzheimer''s disease. Our findings support the use of regional brain atrophy as a preclinical biomarker for LOAD among at-risk individuals. [Copyright &y& Elsevier]