The ENPP1 Q121 Variant Predicts Major Cardiovascular Events in High-Risk Individuals: Evidence for Interaction With Obesity in Diabetic Patients

Insulin resistance (IR) and cardiovascular disease may share a common genetic background. We investigated the role of IR-associated ENPP1 K121Q polymorphism (rs1044498) on cardiovascular disease in high-risk individuals

PARVOVIRUS INFECTION AND KAWASAKI DISEASE: ONE DISEASE FOR TWO SIBLINGS

Introduction: Kawasaki disease (KD) is rarely described in siblings in the same time. In these cases, an infectious trigger must be excluded. Objectives: We describe the clinical course of two brothers who showed severe KD all at once, secondary to Parvovirus infection. Methods: A 9-month-old female showed fever, pallor, vomiting, bilateral non-secreting conjunctivitis, rash. Anamnesis revealed that 12 days before, she had fever, spontaneously resolved. At admission, 9 days after fever onset, she showed fever, conjunctivitis, pharyngitis, rash, and cervical adenopathy. Haematological parameters showed: leukocytosis, neutrophilia; anaemia; CRP: 2.31; ESR: 120. ECG and echocardiography were normal, including coronary Z-scores. She showed positive Parvovirus IgM. Spontaneous defervescence occurred. Further cardiological evaluation was performed to exclude a pericarditis secondary to Parvovirus, and at day 26 after fever onset, coronary artery lesions (CAL) were documented: proximal right coronary artery Z-score of 6.02; left main coronary Z-score: 5.72; left anterior descending Z-score: 5.78. The child was promptly treated with IVIG plus ASA. A further echocardiographic evaluation showed worsening of CAL, with a sacciform aneurysm in the left anterior descending artery (Zscore: 5.08). Laboratory test did not show inflammation; however, the girl was treated with 3 bolus doses of intravenous methylprednisolone (30 mg/kg/dose). The Z-score of CAL did not change and the patient was treated with anakinra (4 mg/kg/day), with a progressive improvement of CAL, and after 2 months, Z-scores normalized. The 7-year-old brother presented fever, vomiting at the same time of the sister, with spontaneous resolution after 4 days. Four days later, he presented again fever with abdominal pain, tachypnoea and tachycardia, secondary anuria. He had: leukocytosis, neutrophilia, anemia; CRP: 0.24; CPK: 773; creatinine: 0.77; BUN: 111; elevated myocardial necrotic enzymes (c-Troponin T: 91.4; Pro-BNP: > 70.000). Echocardiogram showed generalized hypokinesia, a severe reduction of the ejection fraction (EF) (20-25%); increased left atrium (Z-score: 3.3) and mitral valve with moderate insufficiency. He received dopamine, dobutamine, furosemide plus steroids. He showed a constant improvement of echocardiographic parameters, plasmatic enzymes and clinical signs. In 16th day he was discharged with an EF of 45% and persistent septal hypokinesia. However, specific serology anti-Parvovirus was tested and showed increased IgM, with negative IgG. The cardiological outcome revealed a progressive improvement of EF, which reached the 50%. Results: CAL significantly improved after anakinra, at the contrary, the clinical evolution in the brother was different. Conclusion: We describe familial KD in two siblings which had the same infectious trigger (Parvovirus). The brother was diagnosed as a post-viral myocarditis. However, considering the two parallel and different evolution, the girl showed late CAL with aneurisms, and the brother a Kawasaki shock syndrome picture with myocardial dysfunction. Viral illnesses are recognised trigger of KD, and in these cases the rareness is the coincident KD in two siblings, with different and severe clinical course. Noteworthy, the girl had aneurisms which resolved with anakinra, a therapy which has been recently shown to be promising for this disease. Informed consent to publish had been obtained from the parents

Rare-earth elements and yttrium distributions in mangrove coastal water systems: The western Gulf of Thailand

The concentration of rare-earth elements and yttrium (REY) was investigated in dissolved phase, suspended particulate matter, and seafloor sediments of the western coastal area of the Gulf of Thailand. The samples show Eu and Gd positive anomalies in the shale-normalized REY patterns, especially in the suspended particulate matter. On the other hand, a very high REE content was detected in the coastal waters, probably due to the weathering produced by the Mae Klong river waters on rare-earth element (REE)-rich accessory minerals coming from terrains and mineral deposits cropping out in the studied area. The shale-normalized patterns of yttrium and REE estimated for the dissolved phase show an enrichment of medium rare-earth elements (MREE), characteristic of extensive water–rock interactions and weathering occurring in the continental environment. The REE concentrations of suspended particulate, normalized to the REE concentrations in each sediment sampled from the tidal flat, show the same behaviour of the experimentally determined apparent REE bulk distribution coefficients 1 for pH values ranging from about 5.5 to 6.2. Since the REY concentration of the water masses is controlled by the oceanographic features of the studied area, riverine inputs, and ionic straight, we suppose that the dissolved phase represents a mix of truly dissolved and colloidal pool (<0.2 μm) in which REY were enriched during the rock–water interactions of continental environment. In the estuarine system, the salt-induced coagulation of colloidal pool takes place and an authigenic fraction of suspended matter is formed, assuming the typical REE behaviour due to rock–water interactions

Joint effect of insulin signaling genes on cardiovascular events and on whole body and endothelial insulin resistance

Objective: Insulin resistance (IR) and cardiovascular disease (CVD) share a common soil. We investigated the combined role of single nucleotide polymorphisms (SNPs) affecting insulin signaling (ENPP1 K121Q, rs1044498; IRS1 G972R, rs1801278; TRIB3 Q84R, rs2295490) on CVD, age at myocardial infarction (MI), in vivo insulin sensitivity and in vitro insulin-stimulated nitric oxide synthase (NOS) activity. Design and setting: 1. We first studied, incident cardiovascular events (a composite endpoint comprising myocardial infarction-MI, stroke and cardiovascular death) in 733 patients (2186 person-years, 175 events). 2. In a replication attempt, age at MI was tested in 331 individuals. 3. OGTT-derived insulin sensitivity index (ISI) was assessed in 829 individuals with fasting glucose <126 mg/dl. 4. NOS activity was measured in 40 strains of human vein endothelial cells (HUVECs). Results: 1. Risk variants jointly predicted cardiovascular events (HR = 1.181; p = 0.0009) and, when added to clinical risk factors, significantly improved survival C-statistics; they also allowed a significantly correct reclassification (by net reclassification index) in the whole sample (135/733 individuals) and, even more, in obese patients (116/204 individuals). 2. Risk variants were jointly associated with age at MI (p = 0.006). 3. A significant association was also observed with ISI (p = 0.02). 4. Finally, risk variants were jointly associated with insulin-stimulated NOS activity in HUVECs (p = 0.009). Conclusions: Insulin signaling genes variants jointly affect cardiovascular disease, very likely by promoting whole body and endothelium-specific insulin resistance. Further studies are needed to address whether their genotyping help identify very high-risk patients who need specific and/or more aggressive preventive strategies. (C) 2012 Elsevier Ireland Ltd. All rights reserved