Left ventricular "diverticulum" in a patient affected by galactosialidosis.

We present the case of a 35-year-old man affected by the late juvenile form of galactosialidosis. He was known for a moderate pericardial effusion which remained unchanged in the last 12 months. Last follow-up transthoracic echocardiographic examination showed a bulging of the posterior and lateral wall of the left ventricle.

Alogliptin as a third oral antidiabetic drug in patients with type 2 diabetes and inadequate glycaemic control on metformin and pioglitazone: a 52-week, randomized, double-blind, active-controlled, parallel-group study.

Aim: To assess the efficacy and safety of adding alogliptin versus uptitrating pioglitazone in patients with type 2 diabetes and inadequate glycaemic control on metformin and pioglitazone.

Methods: In this randomized, double-blind, active-controlled, parallel-group study, patients with type 2 diabetes and A1c ≥7.0 and ≤10.

Diagnostic sensitivity of thyroid autoantibodies assessed in a population-based, cross-sectional study in adults.

The aim of this study was to estimate the diagnostic sensitivity of thyroid autoantibodies in individuals with a case-mix of subjects with thyroid disease representing that of the general population. We measured thyroid microsome (TMA), thyroid peroxidase (TPO), thyroglobulin (TGA) and thyroid-stimulating hormone (TSH) receptor (TRA) autoantibodies in subjects in the bottom (hyperthyroid end) and top (hypothyroid end) four percentiles of the TSH distribution from among participants in a population-based survey of individuals aged ≥40 years (the Cremona Study). TMA and TPO were the most sensitive autoantibodies in subjects in both the bottom percentiles (19.

High-mobility group box 1 (HMGB1) as a master regulator of innate immunity.

Damage-associated molecular patterns (DAMPs) comprise intracellular molecules characterized by the ability to reach the extracellular environment, where they prompt inflammation and tissue repair. The high-mobility box group 1 (HMGB1) protein is a prototypic DAMP and is highly conserved in evolution. HMGB1 is released upon cell and tissue necrosis and is actively produced by immune cells.

Time for testing incretin therapies in early type 1 diabetes?

Incretin-based compounds, including glucagon-like peptide-1 receptor agonists and dipeptidyl-peptidase-4 inhibitors, have emerged as a new class of agents for the treatment of type 2 diabetes. In this article, the potential and supporting evidence for extending their use to early type 1 diabetes are reviewed. The rationale relies on the assumption that these drugs, in addition to their action on insulin secretion and glucose regulation, may be effective in preserving and even expanding the beta-cell mass.

Metformin--the gold standard in type 2 diabetes: what does the evidence tell us?

Metformin is a cornerstone of oral antidiabetic treatment. Recent joint American and European guidelines recommend instituting metformin therapy along with lifestyle modification at the time type 2 diabetes mellitus (T2DM) is diagnosed. Metformin acts to reduce hepatic gluconeogenesis and improve glucose uptake, and it may exert protective effects on pancreatic islet cells.

Vildagliptin plus metformin combination therapy provides superior glycaemic control to individual monotherapy in treatment-naive patients with type 2 diabetes mellitus.

Aim: To compare the efficacy and safety of vildagliptin and metformin initial combination therapy with individual monotherapies in treatment-naive patients with type 2 diabetes mellitus (T2DM).

Methods: This was a 24-week, randomized, double-blind, active-controlled study. Treatment-naive patients with T2DM who had a glycated haemoglobin (HbA(1c)) of 7.

Frequency-modulated electromagnetic neural stimulation enhances cutaneous microvascular flow in patients with diabetic neuropathy.

Aim: The aim of this study was to investigate the effects of frequency modulated electromagnetic neural stimulation (FREMS), a recently developed safe and effective treatment of painful diabetic neuropathy, on cutaneous microvascular function.

Methods: Thirty-one patients with painful neuropathy were enrolled in a randomised, double-blind, crossover FREMS vs. placebo study; each received two series of 10 treatments of either FREMS or placebo in random sequence within no more than 3 weeks.

Increased intestinal permeability precedes clinical onset of type 1 diabetes.

Aims/hypothesis: Recent observations have shown subclinical intestinal abnormalities in human type 1 diabetes. Whether these are related to the pathogenetic process or secondary to the diabetes remains to be clarified. The aim of this study was to investigate this issue by examining intestinal permeability to sugars in subjects at different stages of type 1 diabetes: preclinical, new-onset and long-term established disease.

Environmental adjuvants, apoptosis and the censorship over autoimmunity.

Alterations during apoptosis lead to the activation of autoreactive T cells and the production of autoantibodies. This article discusses the pathogenic potential of cells dying in vivo, dissecting the role of signals that favor immune responses (adjuvants) and the influence of genetic backgrounds. Diverse factors determine whether apoptosis leads or not to a self-sustaining, clinically apparent autoimmune disease.

HMGB1 is an endogenous immune adjuvant released by necrotic cells.

Immune responses against pathogens require that microbial components promote the activation of antigen-presenting cells (APCs). Autoimmune diseases and graft rejections occur in the absence of pathogens; in these conditions, endogenous molecules, the so-called 'innate adjuvants', activate APCs. Necrotic cells contain and release innate adjuvants; necrotic cells also release high-mobility group B1 protein (HMGB1), an abundant and conserved constituent of vertebrate nuclei.

Tumor destruction and in situ delivery of antigen presenting cells promote anti-neoplastic immune responses: implications for the immunotherapy of pancreatic cancer.

Antigen presenting cells (APCs) activate helper and cytotoxic T cells specific for antigens expressed by tissue cells, including neoplastic cells. This event occurs after the antigen transfer from tissue cells to APC, and is referred to as "cross-presentation". The number and the state of activation of APC in the tumor control the outcome of cross-presentation, including the establishment of protective immune responses.

The disposal of dying cells in living tissues.

Cells continuously die and disappear from the midst of living tissues. However, some of their constituents survive. DNA is horizontally transferred to phagocytic cells, and apoptotic cell antigens shape the immune repertoire.