ARE SUSCEPTIBILITY to INFECTIVE ENDOCARDITIS and EFFECTIVENESS of ANTIBIOTIC PROPHYLAXIS LINKED to FLUCTUATIONS of the IMMUNE SYSTEM? A NOVEL HYPOTHESIS

Introduction: An amendment incorporated into the 2007 AHA and 2009 ESC guidelines on infective endocarditis led to a substantial restriction in indications for the administration of antibiotic prophylaxis. This may have resulted in a subsequent steady increase in the number of cases of infective endocarditis worldwide. Methods: It has been hypothesised that susceptibility to infective endocarditis, together with effectiveness of antibiotic prophylaxis, may be linked to fluctuations of the immune system. Throughout a person’s lifetime, individual susceptibility to infective endocarditis may vary in an identical situation of risk. As a consequence, a personalised targeted approach should be adopted when prescribing antibiotic prophylaxis to prevent onset of endocarditis, taking into account a series of factors including age, comorbidities, cortisol levels, and ethnicity. Children affected by bicuspid aortic valve and injection drug users are amongst the newly-emerging higher risk populations. Conclusion: This up-to-dated narrative review summarizes all the available scientific evidence concerning the variable influence of the immune system on susceptibility to infective endocarditis

CT attenuation analysis of carotid intraplaque hemorrhage

Background and Purpose: Intraplaque hemorrhage is considered a leading parameter of carotid plaque vulnerability. Our purpose was to assess the CT characteristics of intraplaque hemorrhage with histopathologic correlation to identify features that allow for confirming or ruling out the intraplaque hemorrhage. MATERIALS AND METHODS: This retrospective study included 91 patients (67 men; median age, 657 years; age range, 41-83 years) who underwent CT angiography and carotid endarterectomy from March 2010 to May 2013. Histopathologic analysis was performed for the tissue characterization and identification of intraplaque hemorrhage. Two observers assessed the plaque's attenuation values by using an ROI (≤1 and ≥2 mm2). Receiver operating characteristic curve, Mann-Whitney, and Wilcoxon analyses were performed. RESULTS: A total of 169 slices were assessed (59 intraplaque hemorrhage, 63 lipid-rich necrotic core, and 47 fibrous); the average values of the intraplaque hemorrhage, lipid-rich necrotic core, and fibrous tissue were 17.475 Hounsfield units (HU) and 18.407 HU, 39.476 HU and 48.048 HU, and 91.66 HU and 93.128 HU, respectively, before and after the administration of contrast medium. The Mann-Whitney test showed a statistically significant difference of HU values both in basal and after the administration of contrast material phase. Receiver operating characteristic analysis showed a statistical association between intraplaque hemorrhage and low HU values, and a threshold of 25 HU demonstrated the presence of intraplaque hemorrhage with a sensitivity and specificity of 93.22% and 92.73%, respectively. The Wilcoxon test showed that the attenuation of the plaque before and after administration of contrast material is different (intraplaque hemorrhage, lipid-rich necrotic core, and fibrous tissue had P values of .006, .0001, and .018, respectively). CONCLUSIONS: The results of this preliminary study suggest that CT can be used to identify the presence of intraplaque hemorrhage according to the attenuation. A threshold of 25 HU in the volume acquired after the administration of contrast medium is associated with an optimal sensitivity and specificity. Special care should be given to the correct identification of the ROI

Letter regarding the article of Tauzin et al.

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Pulmonary transit time as a marker of diastolic dysfunction in Takotsubo syndrome

AIM: To evaluate the pulmonary transit time (PTT) and its derived parameters using cardiac magnetic resonance imaging (CMRI) as markers of diastolic dysfunction in Takotsubo syndrome (TS) and its relationship with transthoracic echocardiography and CMRI parameters. MATERIALS AND METHODS: Twenty-two patients with TS, who exhibited diastolic dysfunction as assessed by transthoracic echocardiography, were enrolled retrospectively and the PTT, pulmonary transit time index (PTTI), and pulmonary blood volume index (PBVI) were evaluated using first-pass CMRI. PTT was calculated as the number of cardiac cycles required for a bolus of contrast agent to move from the right ventricle (RV) to the left ventricle (LV), whereas PTTI represents the PTT interval corrected for the heart rate. Finally, PBVI was calculated as the product of PTTI, and RV stroke volume indexed for body surface area. Normal references of PTT, PTTI, and PBVI were evaluated in a cohort of 20 age- and sex-matched healthy controls. RESULTS: Compared with healthy subjects, TS patients showed significantly higher PTT, PTTI, and PBVI (p=0.0001, p=0.0001, and p=0.002, respectively). Using multivariable logistic regression, PBVI provided the best differentiation between TS and controls (AUC 0.84). PBVI was significantly associated with the index of diastolic dysfunction and left atrial strain parameters. In addition, PBVI demonstrated a significant correlation with global T2 mapping (r=0,520, p=0,019). CONCLUSION: PTT and the derived parameters, as assessed using first-pass CMRI, are potential tools for assessing LV diastolic dysfunction in patients with TS

Could CMR Tissue-Tracking and Parametric Mapping Distinguish Between Takotsubo Syndrome and Acute Myocarditis? A Pilot Study

Rationale and Objective: Takotsubo syndrome (TS) is a transient and often misdiagnosed form of left ventricular dysfunction. Acute myocarditis (AM) is usually included in TS differential diagnosis. The aim of this study is to assess the role of cardiac magnetic resonance imaging coupled with tissue-tracking technique (CMR-TT) and parametric mappings analysis in discriminating between TS and AM. Materials and Methods: We retrospectively enrolled three groups: patients with TS (n = 12), patients with AM (n = 14), and 10 healthy controls. All the patients had a comprehensive CMR examination, including the assessment of global and segmental longitudinal strain, circumferential strain, radial strain (RS), and parametric mapping. Results: The analysis of variance was used to compare the different groups. In TS patients, basal RS, global T1 mapping, global T2 mapping, mid T2 mapping, apical T1 and T2 mapping were statistically significantly different compared with the other groups. MANCOVA analysis confirmed that the association between myocardial strain data and parametric mapping was independent on age and sex. Apical T1 and T2 mapping proved to have a good performance in differentiating TS from AM (area under the curves of 0.908 and 0.879, respectively). Conclusion: Basal RS and apical tissue mapping analysis are the most advanced CMR-derived parameters in making a differential diagnosis between TS and AM

Delving into the reducing effects of the GABAB positive allosteric modulator, KK-92A, on alcohol-related behaviors in rats

Recent studies have demonstrated the ability of the positive allosteric modulator (PAM) of the GABAB receptor (GABAB PAM), KK-92A, to suppress operant alcohol self-administration and reinstatement of alcohol seeking in selectively bred Sardinian alcohol-preferring (sP) rats. The present study was designed to scrutinize the suppressing effects of KK-92A on alcohol-related behaviors; to this end, four separate experiments were conducted to address just as many new research questions, some of which bear translational value. Experiment 1 found that 7-day treatment with KK-92A (0, 5, 10, and 20 mg/kg, intraperitoneally [i.p.]) effectively reduced alcohol intake in male sP rats exposed to the home-cage 2-bottle "alcohol (10% v/v) vs. water" choice regimen with 1 hour/day limited access, extending to excessive alcohol drinking the ability of KK-92A to suppress operant alcohol self-administration. Experiment 2 demonstrated that the ability of KK-92A to reduce lever-responding for alcohol was maintained also after acute, intragastric treatment (0, 20, and 40 mg/kg) in female sP rats trained to lever-respond for 15% (v/v) alcohol under the fixed ratio 5 schedule of reinforcement. In Experiment 3, acutely administered KK-92A (0, 5, 10, and 20 mg/kg, i.p.) dampened alcohol-seeking behavior in female sP rats exposed to a single session under the extinction responding schedule. Experiment 4 used a taste reactivity test to demonstrate that acute treatment with KK-92A (0 and 20 mg/kg, i.p.) did not alter either hedonic or aversive reactions to a 15% (v/v) alcohol solution in male sP rats, ruling out that KK-92A-induced reduction of alcohol drinking and self-administration could be due to alterations in alcohol palatability. Together, these results enhance the behavioral pharmacological profile of KK-92A and further strengthen the notion that GABAB PAMs may represent a novel class of ligands with therapeutic potential for treating alcohol use disorder

A brief bout of exercise in hypoxia reduces ventricular filling rate and stroke volume response during muscle metaboreflex activation

Purpose: The hemodynamic consequences of exercise in hypoxia have not been completely investigated. The present investigation aimed at studying the hemodynamic effects of contemporary normobaric hypoxia and metaboreflex activation. Methods: Eleven physically active, healthy males (age 32.7 ± 7.2 years) completed a cardiopulmonary test on an electromagnetically braked cycle-ergometer to determine their maximum workload (Wmax). On separate days, participants performed two randomly assigned exercise sessions (3 minutes pedalling at 30% of Wmax): (1) one in normoxia (NORMO), and (2) one in normobaric hypoxia with FiO2 set to 13.5% (HYPO). After each session, the following protocol was randomly assigned: either (1) post-exercise muscle ischemia (PEMI) to study the metaboreflex, or (2) a control exercise recovery session, i.e., without metaboreflex activation. Hemodynamics were assessed with impedance cardiography. Results: The main result was that the HYPO session impaired the ventricular filling rate (measured as stroke volume/diastolic time) response during PEMI versus control condition in comparison to the NORMO test (31.33 ± 68.03 vs. 81.52 ± 49.23 ml·s−1,respectively, p = 0.003). This caused a reduction in the stroke volume response (1.45 ± 9.49 vs. 10.68 ± 8.21 ml, p = 0.020). As a consequence, cardiac output response was impaired during the HYPO test. Conclusions: The present investigation suggests that a brief exercise bout in hypoxia is capable of impairing cardiac filling rate as well as stroke volume during the metaboreflex. These results are in good accordance with recent findings showing that among hemodynamic modulators, ventricular filling is the most sensible variable to hypoxic stimuli

Mixing energy drinks and alcohol during adolescence impairs brain function: A study of rat hippocampal plasticity

In the last decades, the consumption of energy drinks has risen dramatically, especially among young people, adolescents and athletes, driven by the constant search for ergogenic effects, such as the increase in physical and cognitive performance. In parallel, mixed consumption of energy drinks and ethanol, under a binge drinking modality, under a binge drinking modality, has similarly grown among adolescents. However, little is known whether the combined consumption of these drinks, during adolescence, may have long-term effects on central function, raising the question of the risks of this habit on brain maturation. Our study was designed to evaluate, by behavioral, electrophysiological and molecular approaches, the long-term effects on hippocampal plasticity of ethanol (EtOH), energy drinks (EDs), or alcohol mixed with energy drinks (AMED) in a rat model of binge-like drinking adolescent administration. The results show that AMED binge-like administration produces adaptive hippocampal changes at the molecular level, associated with electrophysiological and behavioral alterations, which develop during the adolescence and are still detectable in adult animals. Overall, the study indicates that binge-like drinking AMED adolescent exposure represents a habit that may affect permanently hippocampal plasticity

New perspective for an old drug: Can naloxone be considered an antioxidant agent?

Background: Experimental evidence indicates that Naloxone (NLX) holds antioxidant properties. The present study aims at verifying the hypothesis that NLX could prevent oxidative stress induced by hydrogen peroxide (H2O2) in PC12 cells.Methods: To investigate the antioxidant effect of NLX, initially, we performed electrochemical experiments by means of platinum-based sensors in a cell-free system. Subsequently, NLX was tested in PC12 cells on H2O2induced overproduction of intracellular levels of reactive-oxygen-species (ROS), apoptosis, modification of cells' cycle distribution and damage of cells' plasma membrane.Results: This study reveals that NLX counteracts intracellular ROS production, reduces H2O2-induced apoptosis levels, and prevents the oxidative damage-dependent increases of the percentage of cells in G2/M phase. Likewise, NLX protects PC12 cells from H2O2- induced oxidative damage, by preventing the lactate dehydrogenase (LDH) release. Moreover, electrochemical experiments confirmed the antioxidant properties of NLX.Conclusion: Overall, these findings provide a starting point for studying further the protective effects of NLX on oxidative stress