Host-Guest Interaction Study of Olmesartan Medoxomil with ß-Cyclodextrin Derivatives.

Olmesartan medoxomil (OLM) is a selective angiotensin II receptor antagonist used in the treatment of hypertension. Its therapeutic potential is limited by its poor water solubility, leading to poor bioavailability. Encapsulation of the drug substance by two methylated cyclodextrins, namely randomly methylated ß-cyclodextrin (RM-ß-CD) and heptakis(2,3,6-tri-O-methyl)-ß-cyclodextrin (TM-ß-CD), was carried out to overcome the limitation related to OLM solubility, which, in turn, is expected to result in an improved biopharmaceutical profile. Supramolecular entities were evaluated by means of thermoanalytical techniques (TG-thermogravimetry; DTG-derivative thermogravimetry), spectroscopic methods including powder X-ray diffractometry (PXRD), universal-attenuated total reflectance Fourier-transform infrared (UATR-FTIR) and UV spectroscopy, saturation solubility studies, and by a theoretical approach using molecular modeling. The phase solubility method reveals an AL-type diagram for both inclusion complexes, indicating a stoichiometry ratio of 1:1. The values of the apparent stability constant indicate the higher stability of the host-guest system OLM/RM-ß-CD. The physicochemical properties of the binary systems are different from those of the parent compounds, emphasizing the formation of inclusion complexes between the drug and CDs when the kneading method was used. The molecular encapsulation of OLM in RM-ß-CD led to an increase in drug solubility, thus the supramolecular adduct can be the subject of further research to design a new pharmaceutical formulation containing OLM, with improved bioavailability.

Importance of Multimodality Cardiac Imaging in the Diagnosis of Lipomatous Hypertrophy of the Interatrial Septum-A View beyond Standard Situations.

Lipomatous hypertrophy of the interatrial septum (LHIAS) represents a benign proliferation of lipoid cells at the level of the interatrial septum (IAS) inducing an important thickening of this structure. It respects the fossa ovalis (FO) region, having a typical "hourglass" echocardiographic appearance. There are certain cases though, with unusual appearances and/or with associated pathologies that may induce similar lesions in the heart, in which the differential diagnosis cannot be guaranteed using only the standard methods. The final diagnosis has important implications in these patients' treatment plan. In this paper, we present an unusual case of a female patient undergoing chemotherapy for lung carcinoma, suspected of right atrial thrombosis/metastasis. As the diagnosis was unclear after transthoracic echocardiography (TTE), inducing the suspicion of an IAS mass with atrial wall infiltration, bi- and tridimensional transesophageal echocardiography (TOE) was performed, revealing a severely and homogenously hypertrophied IAS respecting the FO, but lacking a clear visualization of the atrial wall. The diagnosis of LHIAS was established by cardiac magnetic resonance (CMR) that certified the adipose nature of the structure, excluding the need for invasive investigations and/or treatment options. Multimodality imaging is very important for the clinician in adopting the best management plan for each individual patient.

Echocardiographic Myocardial Work: A Novel Method to Assess Left Ventricular Function in Patients with Coronary Artery Disease and Diabetes Mellitus.

Myocardial ischemia caused by coronary artery disease (CAD) and the presence of metabolic abnormalities and microvascular impairments detected in patients with diabetes mellitus (DM) are a common cause of left ventricular (LV) dysfunction. Transthoracic echocardiography is the most-used, non-invasive imaging method for the assessment of myocardial contractility. The accurate evaluation of LV function is crucial for identifying patients who are at high risk or may have worse outcomes. Myocardial work (MW) is emerging as an alternative tool for the evaluation of LV systolic function, providing additional information on cardiac performance when compared to conventional parameters such as left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) because it incorporates deformation and load into its analysis. The potential of MW in various conditions is promising and it has gained increased attention. However, larger studies are necessary to further investigate its role and application before giving an answer to the question of whether it can have widespread implementation into clinical practice. The aim of this review is to summarize the actual knowledge of MW for the analysis of LV dysfunction caused by myocardial ischemia and hyperglycemia.

Considering Both GLS and MD for a Prognostic Value in Non-ST-Segment Elevated Acute Coronary Artery Syndrome.

Global longitudinal strain (GLS) and mechanical dispersion (MD), as determined by 2D speckle tracking echocardiography, have been demonstrated to be reliable indicators of prognosis in a variety of cardiovascular illnesses. There are not many papers that discuss the prognostic significance of GLS and MD in a population with non-ST-segment elevated acute coronary syndrome (NSTE-ACS). Our study objective was to examine the predictive utility of the novel GLS/MD two-dimensional strain index in NSTE-ACS patients. Before discharge and four to six weeks later, echocardiography was performed on 310 consecutive hospitalized patients with NSTE-ACS and effective percutaneous coronary intervention (PCI). Cardiac mortality, malignant ventricular arrhythmia, or readmission owing to heart failure or reinfarction were the major end points. A total of 109 patients (35.16%) experienced cardiac incidents during the follow-up period (34.7 ± 8 months). The GLS/MD index at discharge was determined to be the greatest independent predictor of composite result by receiver operating characteristic analysis. The ideal cut-off value was -0.229. GLS/MD was determined to be the top independent predictor of cardiac events by multivariate Cox regression analysis. Patients with an initial GLS/MD > -0.229 that deteriorated after four to six weeks had the worst prognosis for a composite outcome, readmission, and cardiac death according to a Kaplan-Meier analysis (all p < 0.001). In conclusion, the GLS/MD ratio is a strong indicator of clinical fate in NSTE-ACS patients, especially if it is accompanied by deterioration.

Left Ventricular Remodeling Risk Predicted by Two-Dimensional Speckle Tracking Echocardiography in Acute Myocardial Infarction Patients with Midrange or Preserved Ejection Fraction in Western Romania.

BACKGROUND: Patients with acute myocardial infarction (AMI) are at high risk for left ventricular (LV) remodeling and heart failure. We aimed to study whether LV strains (S) and strain rates (SR) could predict cardiac remodeling in patients with AMI having a midrange or preserved LV ejection fraction (EF) following a percutaneous coronary intervention (PCI) within the first 12 hours from the onset of symptoms. PATIENTS AND METHODS: This is a case-control observational study including patients admitted for their first AMI, either with ST-segment elevation (STEMI) or without ST elevation (NSTEMI), with an LVEF > 40% after a successful PCI. Echocardiography was repeated after 6 months, and the patients were divided into two groups, according to whether LV remodeling was determined on echocardiography. RESULTS: Of the 253 AMI patients (mean 66 aged ± 13 years), including 185 males (73%), 61 (24%) presented signs of LV remodeling. In univariate logistic regression analysis, age, male sex, smoking history, hypertension, hypercholesterolemia, Killip class, renal function, peak creatine phosphokinase - MB level, 2- and 3-vessel coronary artery disease (CAD), and several echocardiographic parameters were significantly associated with LV remodeling (P<0.05). In multivariate logistic regression analysis harmed (H) LS and SR, Killip class, 3-vessel CAD, and LV end-diastolic volume were outlined as independent predictors for LV remodeling. Receiver operating characteristic curve analyses showed that HLS and HLSR were the most powerful independent predictors for LV remodeling (P<0.001), with an area under the curve (AUC) of 0.85 (sensitivity 83%; specificity 84%; p <0.001) and 0.77 (sensitivity 93; specificity 61%; p <0.001), respectively. The identified cut-off values for predictor variables were HLS< -11%, and HLSR< -0.65s-1. CONCLUSION: We concluded that 2D-STE was the best method to evaluate LV remodeling in patients with AMI and midrange or preserved LVEF following myocardial revascularization by a PCI.

The Role of Mitochondrial Reactive Oxygen Species in Cardiovascular Injury and Protective Strategies.

Ischaemia/reperfusion (I/R) injury of the heart represents a major health burden mainly associated with acute coronary syndromes. While timely coronary reperfusion has become the established routine therapy in patients with ST-elevation myocardial infarction, the restoration of blood flow into the previously ischaemic area is always accompanied by myocardial injury. The central mechanism involved in this phenomenon is represented by the excessive generation of reactive oxygen species (ROS). Besides their harmful role when highly generated during early reperfusion, minimal ROS formation during ischaemia and/or at reperfusion is critical for the redox signaling of cardioprotection. In the past decades, mitochondria have emerged as the major source of ROS as well as a critical target for cardioprotective strategies at reperfusion. Mitochondria dysfunction associated with I/R myocardial injury is further described and ultimately analyzed with respect to its role as source of both deleterious and beneficial ROS. Furthermore, the contribution of ROS in the highly investigated field of conditioning strategies is analyzed. In the end, the vascular sources of mitochondria-derived ROS are briefly reviewed.