Cadherin 2-Related Arrhythmogenic Cardiomyopathy: Prevalence and Clinical Features.

Background: Arrhythmogenic cardiomyopathy (ACM) is an inherited cardiac disease characterized by fibrofatty replacement of the right and left ventricle, often causing ventricular dysfunction and life-threatening arrhythmias. Variants in desmosomal genes account for up to 60% of cases. Our objective was to establish the prevalence and clinical features of ACM stemming from pathogenic variants in the nondesmosomal cadherin 2 (CDH2), a novel genetic substrate of ACM.

Use of dual-flow bioreactor to develop a simplified model of nervous-cardiovascular systems crosstalk: A preliminary assessment.

Chronic conditions requiring long-term rehabilitation therapies, such as hypertension, stroke, or cancer, involve complex interactions between various systems/organs of the body and mutual influences, thus implicating a multiorgan approach. The dual-flow IVTech LiveBox2 bioreactor is a recently developed inter-connected dynamic cell culture model able to mimic organ crosstalk, since cells belonging to different organs can be connected and grown under flow conditions in a more physiological environment. This study aims to setup for the first time a 2-way connected culture of human neuroblastoma cells, SH-SY5Y, and Human Coronary Artery Smooth Muscle Cells, HCASMC through a dual-flow IVTech LiveBox2 bioreactor, in order to represent a simplified model of nervous-cardiovascular systems crosstalk, possibly relevant for the above-mentioned diseases.

Calmodulin mutations and life-threatening cardiac arrhythmias: insights from the International Calmodulinopathy Registry.

Aims: Calmodulinopathies are rare life-threatening arrhythmia syndromes which affect mostly young individuals and are, caused by mutations in any of the three genes (CALM 1-3) that encode identical calmodulin proteins. We established the International Calmodulinopathy Registry (ICalmR) to understand the natural history, clinical features, and response to therapy of patients with a CALM-mediated arrhythmia syndrome.

Methods And Results: A dedicated Case Report File was created to collect demographic, clinical, and genetic information.

Calmodulinopathy: Functional Effects of CALM Mutations and Their Relationship With Clinical Phenotypes.

In spite of the widespread role of calmodulin (CaM) in cellular signaling, CaM mutations lead specifically to cardiac manifestations, characterized by remarkable electrical instability and a high incidence of sudden death at young age. Penetrance of the mutations is surprisingly high, thus postulating a high degree of functional dominance. According to the clinical patterns, arrhythmogenesis in CaM mutations can be attributed, in the majority of cases, to either prolonged repolarization (as in long-QT syndrome, LQTS phenotype), or to instability of the intracellular Ca store (as in catecholamine-induced tachycardias, CPVT phenotype).

Calmodulinopathy: A Novel, Life-Threatening Clinical Entity Affecting the Young.

Sudden cardiac death (SCD) in the young may often be the first manifestation of a genetic arrythmogenic disease that had remained undiagnosed. Despite the significant discoveries of the genetic bases of inherited arrhythmia syndromes, there remains a measurable fraction of cases where in-depth clinical and genetic investigations fail to identify the underlying SCD etiology. A few years ago, 2 cases of infants with recurrent cardiac arrest episodes, due to what appeared to be as a severe form of long QT syndrome (LQTS), came to our attention.

Corrigendum to "Chemokines and Heart Disease: A Network Connecting Cardiovascular Biology to Immune and Autonomic Nervous Systems".

[This corrects the article DOI: 10.1155/2016/5902947.].

The genetics underlying idiopathic ventricular fibrillation: A special role for catecholaminergic polymorphic ventricular tachycardia?

Background: Ventricular fibrillation (VF) is a major cause of sudden cardiac death. In some cases clinical investigations fail to identify the underlying cause and the event is classified as idiopathic (IVF). Since mutations in arrhythmia-associated genes frequently determine arrhythmia susceptibility, screening for disease-predisposing variants could improve IVF diagnostics.

Desmoplakin missense and non-missense mutations in arrhythmogenic right ventricular cardiomyopathy: Genotype-phenotype correlation.

Background: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is traditionally considered as primarily affecting the right ventricle. Mutations in genes encoding desmosomal proteins account for 40-60% of cases. Genotype-phenotype correlations are scant and mostly non gene-specific.

Chemokines and Heart Disease: A Network Connecting Cardiovascular Biology to Immune and Autonomic Nervous Systems.

Among the chemokines discovered to date, nineteen are presently considered to be relevant in heart disease and are involved in all stages of cardiovascular response to injury. Chemokines are interesting as biomarkers to predict risk of cardiovascular events in apparently healthy people and as possible therapeutic targets. Moreover, they could have a role as mediators of crosstalk between immune and cardiovascular system, since they seem to act as a "working-network" in deep linkage with the autonomic nervous system.

Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.

The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization.

Long QT syndrome-associated mutations in intrauterine fetal death.

Importance: Intrauterine fetal death or stillbirth occurs in approximately 1 out of every 160 pregnancies and accounts for 50% of all perinatal deaths. Postmortem evaluation fails to elucidate an underlying cause in many cases. Long QT syndrome (LQTS) may contribute to this problem.

Hypertension and sensorimotor peripheral neuropathy in type 2 diabetes.

Background: The mechanisms responsible for the onset of sensorimotor peripheral diabetic neuropathy (SMPN) remain largely unknown. To address this issue, we studied the relationship between traditional cardiovascular risk factors, parameters of metabolic control, and the presence of SMPN in patients with type 2 diabetes of relatively short duration.

Methods: Blood pressure, glycated hemoglobin, lipid profile, and the presence of micro- and macrovascular complications were assessed and monitored in 31 consecutive ambulatory patients with type 2 diabetes (age 60.

High rate of neoplasia and other co-morbid conditions in type-2 diabetic patients with longer duration of disease and poor metabolic control.

Aim: The aim of the study was to assess the rate of neuroendocrine malignancies in the gastrointestinal tract, other malignancies and mitotic processes, in type-2 diabetic patients. In particular, we tested the hypothesis that a poor metabolic control is associated with a higher rate of neoplasms and other co-morbid conditions, such as hypertension and peripheral neuropathy.

Methods: Forty-one consecutive asymptomatic type-2 diabetic outpatients were followed for 8 years and clustered in 2 groups, according to disease duration, insulin need, and dose of oral antidiabetic agents.

Relative preservation of the renin-angiotensin-aldosterone system response to active orthostatism in type 2 diabetic patients with autonomic neuropathy and postural hypotension.

Objective: The pathophysiological mechanisms involved in the progression of autonomic neuropathy (AN) and development of postural hypotension (PH) in type 2 diabetes (T2D) are largely unknown. The aim of this study was to address this issue by investigating the neurohormonal responses during active orthostatism (O) in T2D patients with and without PH.

Methods: Plasma noradrenaline (NA, pmol/L), adrenaline (A, pmol/L), plasma renin activity (PRA, angiotensin I, nmol/L/h) and aldosterone (ALD, pmol/L) were measured in the supine position (baseline) and after 2, 5, and 20 min O in 10 healthy subjects (C), 9 T2D patients without AN (D), 14 T2D patients with AN and without PH (DAN), and 7 T2D patients with AN and PH (DAN-PH).

Helicobacter pylori prevalence in patients with diabetes and its relationship to dyspeptic symptoms.

As available data on Helicobacter pylori infection in patients with diabetes are scattered and discordant, we evaluated the prevalence of H. pylori and its relationship to dyspeptic symptoms in adult patients with diabetes and subjects with dyspepsia. H.

[Study of the onset and progression of peripheral neuropathy and hypertension in NIDDM].

Background: Diabetic neuropathy is the most common pathology affecting the peripheral nervous system. In prognostic terms, it is the most devastating complication of diabetes. About 50% of diabetics suffer from neuropathy between 25-30 years after the diagnosis of diabetes, even if over the past few decades there has been a considerable improvement in the diagnostic methods and criteria used to classify peripheral neuropathies, many of which are related to the development of neurophysiology.

Lower frequency of sister chromatid exchanges and altered frequency of HLA B-region alleles among individuals with sporadic dysplastic nevi.

Sister chromatid exchanges (SCE) were analyzed in peripheral blood lymphocytes of 24 individuals, following diagnosis, and prior to surgical removal, of a sporadic dysplastic nevus (DN). Lower SCE values and variability were found in 23 sporadic DN individuals compared with controls (2.52 +/- 0.

The in vitro production of thromboxane B2 by platelets of diabetic patients is normal at physiological concentrations of ionized calcium.

Platelets of patients with diabetes and no evidence of macroangiopathy produce normal amounts of thromboxane (Tx) B2 in vivo, whereas they usually show increased production in vitro. Since in vitro studies have been usually performed in citrated PRP, we tested the hypothesis that the discrepancy between in vivo and in vitro studies is due to the low concentration of plasma ionized calcium ([Ca2+]o) that is present in citrated PRP. In fact, low [Ca2+]o artifactually potentiates the platelet TxB2 production in vitro.

Sister chromatid exchange analysis in familial groups of malignant melanoma patients.

Sister chromatid exchange (SCE) analysis was carried out on peripheral blood lymphocytes of 20 familial malignant melanoma (FMM) and 39 sporadic malignant melanoma (SMM) untreated patients, belonging to 10 and 39 families, respectively. The study was extended to 39 unaffected close relatives of FMM patients, to 187 unaffected close relatives of SMM patients, and to 20 unaffected unrelated individuals (control group), all examined under the same conditions. The mean SCE rates/cell were significantly higher in MM families than in the control group, and in melanoma patients than in their close relatives.

HLA study of 21 families with two or more members affected by febrile convulsions.

21 Italian families with at least two members who had had febrile convulsions (FC) were HLA-typed for class I antigens. A total of 49 subjects and 43 close relatives (parents or sibs) were examined. No single antigen or haplotype was statistically more frequent among pooled FC subjects.

Double minute chromosomes and a homogeneously staining chromosome region in C3H10T1/2 murine cells transformed "in vitro" by proton radiation.

Four foci (type II or type III) of transformed cells, isolated from the murine line C3H10T1/2 after exposure to proton radiations, were expanded and cytogenetically examined. While the overall numerical chromosome distributions were similar, there were some differences between the various cell lines with regard to the presence and frequency of specific-marker chromosomes and to the colony-forming efficiency in soft-agarose medium. No association between any of these markers and the transformed phenotype could be established.

Sister chromatid exchange in methotrexate resistant and sensitive C3H10T1/2 mouse cells.

Sister chromatid exchange (SCE) induction by methotrexate (MTX) was analyzed in C3H10T1/2 clone 8 mouse cells and in two MTX-resistant subclones with numerous double minute chromosomes (DM) present in the majority of cells. Significantly higher SCE levels were found, as expected, in sensitive cells after treatments with 10(-2) or 10(-5) M MTX but not in resistant cells permanently growing in the presence of a high concentration of MTX (2 x 10(-3) M) and characterized by a markedly lower cell cycle replication index (R.I.

[Afterload changes in diabetic dysautonomia evaluated using echocardiography].

We have studied echocardiographic morpho-functional alterations in 34 male subjects with diabetes, aged 31-73 years, with and without autonomic nervous system failure. The subjects are grouped following the tests "deep breathing", "Valsalva manoeuver", "lying to standing" and "active standing" in: D-I (10 normal subjects); D-II (16 subjects with parasympathetic failure); D-III (8 subjects with orthosympathetic failure). The D-III subjects showed significantly lower parietal systolic stress (PSS) compared to normal subjects, 115.