Nailfold capillaroscopy reveals early peripheral microcirculation abnormalities in children affected by heterozygous familial hypercholesterolemia.

Background: nailfold capillaroscopy (NCF) is a non-invasive imaging technique to seek peripheral microcirculation abnormalities in children and adults. Familial hypercholesterolemia is a genetic disorder caused by mutations capable of increasing blood levels of low-density lipoproteins cholesterol (LDL-C), thus triggering early atherosclerosis. The study aims at evaluating peripheral microcirculation in children with heterozygous familial hypercholesterolemia (HeFH) by means of NFC in comparison with healthy peers and at searching for possible correlations between these abnormalities and patients' lipid panel.

Assessment of Biventricular Function by Three-Dimensional Speckle Tracking Echocardiography in Adolescents and Young Adults with Human Immunodeficiency Virus Infection: A Pilot Study.

Background: The purpose of the study was to assess biventricular parameters of wall deformation with three-dimensional speckle tracking echocardiography (3DSTE) in adolescents and young adults with human immunodeficiency virus (HIV) infection on antiretroviral therapy in order to detect a possible subclinical myocardial dysfunction.

Methods: Twenty-one patients aged 12-39 years with HIV, 21 normal controls of the same age and sex, and 21 patients with idiopathic nonischemic dilated cardiomyopathy (DCM) were studied with 3DSTE. All HIV patients were stable in terms of HIV infection, with no history of heart disease or other chronic systemic disease except HIV infection, and were on highly active antiretroviral therapy with good immunological control.

Bi-Atrial Function before and after Percutaneous Closure of Atrial Septum in Patients with and without Paroxysmal Atrial Fibrillation: A 2-D and 3-D Speckle Tracking Echocardiographic Study.

Our aim was to analyze atrial function with 2-D (2-D-STE) and 3-D (3-D-STE) speckle tracking echocardiography in patients with atrial septal devices and paroxysmal atrial fibrillation (PAF). One hundred sixteen patients and a subgroup of 22 patients who developed PAF after device insertion were studied. Left atrial and right atrial peak longitudinal strain and standard deviations of time to peak strain (TPS) were calculated using 2-D-STE.

Assessment of Biventricular Function by Three-Dimensional Speckle-Tracking Echocardiography in Secondary Mitral Regurgitation after Repair with the MitraClip System.

Background: The goal of this study was to determine changes in left ventricular (LV) and right ventricular (RV) function with three-dimensional (3D) speckle-tracking echocardiography (STE) after percutaneous mitral valve repair with the MitraClip system in high-risk surgical patients with moderate to severe or severe secondary mitral regurgitation (MR).

Methods: Thirty-two patients with MR undergoing MitraClip were prospectively included. Patients underwent two-dimensional (2D) and 3D transthoracic echocardiography before clip implantation and after 6-month follow-up.

Echocardiographic findings in simple and complex patent foramen ovale before and after transcatheter closure.

Aims: Percutaneous closure of patent foramen ovale (PFO) in cryptogenic cerebrovascular events is an alternative to medical therapy. The interpretation of residual shunts after implantation of different devices for PFO with different morphologies is controversial.

Methods And Results: Transcatheter PFO closure was performed in 123 patients with a history of ≥1 paradoxical embolism using three different devices: Amplatzer (n = 46), Figulla Occlutech (n = 41), and Atriasept Cardia (n = 36).

Comprehensive assessment of biventricular function and aortic stiffness in athletes with different forms of training by three-dimensional echocardiography and strain imaging.

Aims: Previous studies have shown distinct models of cardiac adaptations to the training in master athletes and different effects of endurance and strength-training on cardiovascular function. We attempted to assess left-ventricular (LV) function, aortic (Ao) function, and right-ventricular (RV) function in athletes with different forms of training by using three-dimensional (3D) echocardiography, tissue Doppler imaging (TDI) and speckle-tracking imaging (STI).

Methods And Results: We examined 35 male marathon runners (endurance-trained athletes, ETA), 35 powerlifting athletes (strength-trained athletes, STA), 35 martial arts athletes (mixed-trained athletes, MTA), and 35 sedentary untrained healthy men (controls, CTR).

Cardiological assessment of cardiac patients undergoing non-cardiac surgery (usefulness of surveys).

Aim Of The Study: The aim of the study was to considerate the effective usefulness of preoperative stress test and echocardiography in adult patients with coronary artery disease, undergoing non-cardiac surgery.

Materials And Methods: In the last three years, 200 patients aged 58-85, affected by stable ischemic pathology, undergoing non cardiac surgery, and treated with oral drugs, were enrolled for an assessment orotocol including anamnesis, objective examination, blood pressure, RCG, blood chemistry analysis, and was performed a cardiac risk evaluation. A second 50 patients control cohort of the same class was subjected to the same tests, and preoperative and exercise stress test.

High performance liquid chromatographic determination of thalidomide in patients affected by hepatocellular carcinoma.

The present study developed a validate and precise reversed-phase high performance liquid chromatography (HPLC) method for the determination of thalidomide (T) in plasma, to quantify T in patients affected by hepatocellular carcinoma. Twelve male subjects aging from 62 to 82 years and weighting 66-88kg, were orally administered with single dose of T (200mg/BW). Two ml of stabilizer-solution (CH3OH/CH3CN, 1/1 (v/v)+CH3COOH 2%) were added to 1ml of human plasma and stoked to -80 degrees C until analyses.

Use of capillary electrophoresis and poly(ethylene oxide) as the coating agent for the determination of substances related to heroin addiction and treatment.

The purpose of this study was to identify and quantify morphine, codeine, methadone, and 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine using capillary electrophoresis in urine specimens. Adequate peak separation was achieved using nearly neutral pH phosphate buffer and poly(ethylene oxide) as the coating agent. This dynamic coating of the inner surface of the capillary was obtained by rinsing with a solution containing this compound.

Synthesis of stable analogues of geranylgeranyl diphosphate possessing a (Z,E,E)-geranylgeranyl side chain, docking analysis, and biological assays for prenyl protein transferase inhibition.

Herein, we report the synthesis of novel stable analogues of geranylgeranyl diphosphate (GGPP), in which the "natural" all-trans geranylgeranyl portion has been replaced by a (Z,E,E)-geranylgeranyl chain. The change in configuration and consequent change in the relative position of the polar portion with the lipophilic side chain did not improve the properties of the E,E,E analogues in their inhibition of geranylgeranyl protein transferase I (GGTase I). However, a significant level of GGTase I inhibition and selectivity for GGTase I over farnesyl transferase (FTase) was maintained the unsubstituted phosphonoacetamidoxy derivative 4 a.

Synthesis of anthranylaldoxime derivatives as estrogen receptor ligands and computational prediction of binding modes.

N-Me-anthranylaldoximes possess a hydrogen-bonded pseudocyclic A' ring in place of the typical phenolic A-ring that is characteristic of most estrogen receptor (ER) ligands. We have investigated the role played by substituents introduced into either one or both of the peripheral 3- and 4-phenyl rings in modulating ER binding affinity. An efficient synthetic strategy was employed for the preparation of differentially substituted 3- and 4-aryl derivatives that involved exploiting the different reactivity of bromo- versus chloro-aryl groups in palladium-catalyzed cross-couplings.

Variously substituted (phosphonoacetamido)oxy analogues of geranylgeranyl diphosphate (GGdP) as GGdP-transferase (GGTase) inhibitors and antiproliferative agents.

Aberrant signalling through the pathways of small GTP-binding proteins, belonging to the Ras superfamily (Ras, Rho, Rac, Cdc42 etc.), occurs in several types of cancer, where mutated Ras accumulates in its GTP-bound active form and causes uncontrolled cell proliferation. For these reasons, molecules able to target the Ras pathway in any of its stages are potentially useful in anti-cancer therapies.

Synthesis of a resveratrol analogue with high ceramide-mediated proapoptotic activity on human breast cancer cells.

Resveratrol, a natural product with a stilbene structure, exerts profound proapoptotic activity in human cancer cells, by triggering the accumulation of ceramide, a bioactive sphingolipid. We studied the biological effects of seven methoxylated and/or naphthalene-based resveratrol analogues and compared these compounds with resveratrol with the objective to identify an analogue with higher ceramide-mediated proapoptotic activity relative to resveratrol. Here we show that the compound with three hydroxyls and a naphthalene ring is the most effective in triggering apoptosis coupled to the induction of endogenous ceramide in human cancer cells.

Phosphonomethylphosphorylmethyl(oxy)-analogues of geranylgeranyl diphosphate as stable and selective geranylgeranyl protein transferase inhibitors.

The diphosphate moiety of geranylgeranyldiphosphate (GGdP) was replaced with metabolically and hydrolytically stable analogous polar portions, in an attempt to obtain new geranylgeranyltransferase (GGTase) inhibitors, which could also be selective over congener enzyme farnesyltransferase (FTase). In particular, the phosphonomethylphosphorylmethoxy derivative showed the highest inhibition potency, accompanied by a satisfactory GGTase/FTase selectivity.

Stable propylphosphonic acid analogues of geranylgeranyl diphosphate possessing inhibitory activity on geranylgeranyl protein transferase.

Stable analogues of geranylgeranyl diphosphate, possessing 3-(phosphono)propionamido moieties in the place of the metabolically unstable diphosphate portion, were prepared and submitted to prenyltransferase (GGTase and FTase) inhibition assays. In one case, an excellent GGTase inhibitory activity was obtained (IC(50) = 39 nM), accompanied by a certain degree of GGTase vs. FTase selectivity.

Diaryl-substituted salicyl- and anthranyl-ketoximes as potential estrogen receptor ligands.

3,4-diphenylsalicylaldoxime and 3,4-diphenylanthranylaldoxime derivatives, containing small groups (methyl or ethyl) on the imine carbon atom, were synthesized and submitted to biological assays. Binding tests performed on uterine cytosol estrogen receptor (ER) preparation and on purified full-length human ERalpha and ERbeta, showed that the newly synthesised compounds exhibit considerably lower binding affinities with respect to reference non-substituted 3,4-salicylaldoxime.

Efficient application of monolithic silica column to determination of illicit heroin street sample by HPLC.

In this paper, an HPLC method is proposed for a routine, rapid and simple analysis of heroin samples confiscated from the illicit market, based on a new type of packing for HPLC columns (monolithic silica). Acetonitrile and pH 3.5 phosphate buffer solution were used under both isocratic and gradient conditions.

Stable analogues of geranylgeranyl diphosphate possessing improved geranylgeranyl versus farnesyl protein transferase inhibitory selectivity.

Phosphonoacetamido(oxy) groups have proven to be good mimics of the diphosphate portion in geranylgeranyl protein transferase I (GGTase I) inhibitors. The introduction of small alkyl groups (Me, Et) into the diphosphate mimic moiety caused a further decrease in collateral farnesyl protein transferase (FTase) inhibitory activity, thereby improving GGTase I over FTase selectivity.

Synthesis of aniline-type analogues of farnesyl diphosphate and their biological assays for prenyl protein transferase inhibitory activity.

Stable analogues of farnesyl diphosphate, possessing an aniline-type portion in the prenyl-mimic moiety and phosphonoacetamido(oxy) groups in the place of the metabolically unstable diphosphate unit, were synthesised and submitted to biological assays. The enzyme inhibition tests performed on FTase and GGTase I show that the newly synthesised compounds based on a combination of the aniline-containing portions with (phosphonoacetamido)oxy groups do not afford potent inhibitors.

Novel estrogen receptor ligands based on an anthranylaldoxime structure: role of the phenol-type pseudocycle in the binding process.

The 3,4-diphenylsalicylaldoxime system 1 is an estrogen receptor (ER) ligand of unusual structure, having a hydrogen-bonded pseudocyclic A'-ring in place of the paradigmatic phenolic A-ring that is characteristic of most estrogens. We have investigated the role played by the pseudocycle A' in binding to the ER by preparing 3,4-diphenylbenzaldoxime (4), a compound that completely lacks this ring but still preserves all of the other features of the original molecule 1, as well as a series of 3,4-diphenylanthranylaldoximes (5a-c) in which the nature of the heteroatom participating in the formation of pseudoring A' has been changed from an oxygen (1) to a nitrogen that is either unsubstituted (5a) or substituted with small alkyl groups (a methyl in 5b, or an ethyl in 5c). The importance of hydrogen-bonded pseudocycle A' in the binding process was confirmed by the fact that benzaldoxime 4 showed a greatly reduced binding affinity compared to salicylaldoxime 1.

Myocardial cytoprotection by trimetazidine against anthracycline-induced cardiotoxicity in anticancer chemotherapy.

The ability of trimetazidine (2,3,4, trimethoxybenzylpiperazine dihydrochloride, TMZ) to protect the myocardium against anthracycline (ANT)-induced cardiotoxicity during chemotherapy has been evaluated in female patients with breast cancer. A clinical trial was conducted in 61 patients subdivided into three groups: group 1 (n = 15, G1 ) treated with standard ANT protocol and cardioprotection by dexrazoxane (DEX) plus TMZ (60 mg, daily dose); group 2 (n = 22, G2) treated with ANT and cardioprotection by TMZ only; and group 3 (n = 24, G3) scheduled to receive ANT therapy and DEX. All the patients submitted to an echocardiographic evaluation of diastolic function (E wave velocity, A wave velocity, isovolumetric relaxation time [IVRT], deceleration time [DT]) at enrollment (T0), at T1 time, at T2 time, and at T3 time.

Short-term effect of exercise on platelet factor 4 in normal subjects and in patients with coronary artery disease.

Background: The aim of this study was to evaluate the plasma concentration of a platelet-derived protein, platelet factor 4 (PF4), before and after exercise in coronary artery disease.

Methods: We enrolled 60 patients with documented ischemic heart disease. The subjects were divided into two groups: Group 1 patients with previous myocardial infarction (n = 20, 13 males, 7 females, mean age 51.