Immunotheraphy in Allergic Diseases.

The prevalence of allergic diseases is increasing worldwide. It is estimated that more than 30% of the world population is now affected by one or more allergic conditions and a high proportion of this increase is in young people. The diagnosis of allergy is dependent on a history of symptoms on exposure to an allergen together with the detection of allergen-specific IgE.

Monitoring T-Cell Responses in Translational Studies: Optimization of Dye-Based Proliferation Assay for Evaluation of Antigen-Specific Responses.

Adoptive therapy with regulatory T cells or tolerance-inducing antigen (Ag)-presenting cells is innovative and promising therapeutic approach to control undesired and harmful activation of the immune system, as observed in autoimmune diseases, solid organ and bone marrow transplantation. One of the critical issues to elucidate the mechanisms responsible for success or failure of these therapies and define the specificity of the therapy is the evaluation of the Ag-specific T-cell responses. Several efforts have been made to develop suitable and reproducible assays.

Long-term outcomes with agalsidase alfa enzyme replacement therapy: Analysis using deconstructed composite events.

This is a retrospective analysis of Fabry Outcome Survey data from children/adults ( = 677) receiving agalsidase alfa enzyme replacement therapy for a median of 3 years, examining cerebrovascular, cardiac, and renal morbidity endpoints separately. Cardiac events occurred at younger ages than cerebrovascular or renal events, cerebrovascular events were more frequent in females than males, and males were more likely to experience cardiac and renal events at a younger age than females.

β-Thromboglobulin may not reflect platelet activation during haemodialysis with the HeprAN membrane.

Background: When blood passes through the extracorporeal circuit during haemodialysis (HD) undesirable effects including platelet degranulation and coagulation activation take place. β-thromboglobulin (β-TG) is a sensitive marker of platelet activation. The aim of this study was to investigate platelet degranulation and coagulation activation during HD with the heparin-coated dialysis membrane HeprAN.

Cardiotoxic Effects of Short-Term Doxorubicin Administration: Involvement of Connexin 43 in Calcium Impairment.

The use of Doxorubicin (DOXO), a potent antineoplastic agent, is limited by the development of cardiotoxicity. DOXO-induced cardiotoxicity is multifactorial, although alterations in calcium homeostasis, seem to be involved. Since even the Connexin43 (Cx43) plays a pivotal role in these two phenomena, in this study we have analyzed the effects of DOXO on Cx43 expression and localization.

Metabolomics and Heart Diseases: From Basic to Clinical Approach.

Background: The field of metabolomics has been steadily increasing in size for the last 15 years. Advances in analytical and statistical methods have allowed metabolomics to flourish in various areas of medicine. Cardiovascular diseases are some of the main research targets in metabolomics, due to their social and medical relevance, and also to the important role metabolic alterations play in their pathogenesis and evolution.

The effect of intracoronary infusion of bone marrow-derived mononuclear cells on all-cause mortality in acute myocardial infarction: rationale and design of the BAMI trial.

Over the past 13 years bone marrow-derived mononuclear cells (BM-MNCs) have been widely investigated for clinical efficacy in patients following acute myocardial infarction (AMI). These early phase II trials have used various surrogate markers to judge efficacy and, although promising, the results have been inconsistent. The phase III BAMI trial has therefore been designed to demonstrate that intracoronary infusion of BM-MNCs is safe and will significantly reduce the time to first occurrence of all-cause death in patients with reduced left ventricular ejection fraction after successful reperfusion for ST-elevation AMI (powered with the aim of detecting a 25% reduction in all-cause mortality).

Comparison of Electrocardiographic Characteristics in Men Versus Women ≤ 55 Years With Acute Myocardial Infarction (a Variation in Recovery: Role of Gender on Outcomes of Young Acute Myocardial Infarction Patients Substudy).

Young women with acute myocardial infarction (AMI) have a worse prognosis than their male counterparts. We searched for differences in the electrocardiographic presentation of men and women in a large, contemporary registry of young adults with AMI that could help explain gender differences in outcomes. The qualifying electrocardiogram was blindly assessed by a central core lab in 3,354 patients (67% women) aged 18 to 55 years included in the Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients study.

Effect of greater trochanteric epiphysiodesis after femoral varus osteotomy for lateral pillar classification B and B/C border Legg-Calvé-Perthes disease: A retrospective observational study.

This is a retrospective observational study. Greater trochanteric epiphysiodesis (GTE) has been recommended to prevent Trendelenburg gait and limitation of the hip joint motion due to trochanteric overgrowth after femoral varus osteotomy (FVO) in Legg-Calvé-Perthes disease (LCPD). However, capital femoral physeal arrest frequently occurs in patients with severe disease (lateral pillar C), so GTE might not be as effective in these patients.

Attenuation of MUC4 potentiates the anticancer activity of auranofin via regulation of the Her2/Akt/FOXO3 pathway in ovarian cancer cells.

Previously, we reported that auranofin induces apoptosis in SKOV3 cells via regulation of the IKKβ/FOXO3 pathway. In the present study, we reveal that the anticancer activity of auranofin in SKOV3 cells could be enhanced by the attenuation of MUC4 through the regulation of the Her2/Akt/FOXO3 pathway. Compared to the control-siRNA, siRNA transfection against MUC4 into SKOV3 cells accelerated the protein degradation of Her2.

Individual and co-expression patterns of nerve growth factor and heme oxygenase-1 predict shorter survival of gastric carcinoma patients.

Background: Nerve growth factor (NGF) is a neurotrophic factor which regulates cell development and proliferation. Recently, it has been suggested that NGF induces heme oxygenase-1 (HO1) expression, and that both NGF and HO1 are involved in the progression of malignant human tumors. However, exact roles of NGF and HO1 in tumorigenesis remain controversial.

Expression of epithelial-mesenchymal transition and cancer stem cell markers in colorectal adenocarcinoma: Clinicopathological significance.

Epithelial-mesenchymal transition (EMT) is known to be associated with cancer progression, metastatic spread, and therapeutic resistance and to occur at the invasive front. Cancer stem cells (CSCs) display stemness features and might be implicated in tumor initiation, local recurrence and metastasis. The present study was conducted to examine the expression status and relationships between EMT- and CSC-related proteins in the different tumor areas of primary colorectal cancer (CRC), along with their clinicopathological significance.

Overexpression of SIRT1 prevents hypoxia‑induced apoptosis in osteoblast cells.

Hypoxic‑ischemic injury of the bone results in osteonecrosis. Nicotinamide adenosine dinucleotide (NAD)‑dependent deacetylase sirtuin‑1 (SIRT1), a type of NAD‑dependent deacetylase, is involved in multiple biological functions, particularly in anti‑apoptosis. However, the effects of SIRT1 in osteoblasts remain unclear and whether SIRT1 protects osteoblasts in hypoxic conditions remains to be elucidated.

Mitochondrial Cx43, an important component of cardiac preconditioning.

Connexin 43 (Cx43) forms gap junction channels that are essential for the propagation of electrical depolarization in cardiomyocytes, but also with important roles in the pathophysiology of reperfusion injury. However, more recent studies have shown that Cx43 has also important functions independent from intercellular communication between adjacent cardiomyocytes. Some of these actions have been related to the presence of Cx43 in the mitochondria of these cells (mitoCx43).

FAM83H is involved in the progression of hepatocellular carcinoma and is regulated by MYC.

Recently, the roles of FAM83H in tumorigenesis have been interested and increased expression of FAM83H and MYC in hepatocellular carcinoma (HCC) have been reported. Therefore, we investigated the expression and role of FAM83H in 163 human HCCs and further investigated the relationship between FAM83H and oncogene MYC. The expression of FAM83H is elevated in liver cancer cells, and nuclear expression of FAM83H predicted shorter survival of HCC patients.

Correlation between trough serum levels of adalimumab and absolute PASI score in a series of patients with psoriasis.

Background: The possibility of monitoring serum drug levels has opened the door to optimising biologic therapy. To consolidate this advance, it is imperative to demonstrate an adequate correlation between serum drug levels and clinical course.

Objectives: To investigate whether a correlation exists between adalimumab levels and clinical response measured as absolute PASI.

Lysyl oxidase overexpression accelerates cardiac remodeling and aggravates angiotensin II-induced hypertrophy.

Lysyl oxidase (LOX) controls matrix remodeling, a key process that underlies cardiovascular diseases and heart failure; however, a lack of suitable animal models has limited our knowledge with regard to the contribution of LOX to cardiac dysfunction. Here, we assessed the impact of LOX overexpression on ventricular function and cardiac hypertrophy in a transgenic LOX (TgLOX) mouse model with a strong cardiac expression of human LOX. TgLOX mice exhibited high expression of the transgene in cardiomyocytes and cardiofibroblasts, which are associated with enhanced LOX activity and HO production and with cardiofibroblast reprogramming.

Delayed, oral pharmacological inhibition of calpains attenuates adverse post-infarction remodelling.

Unlabelled: Calpains activate during myocardial ischemia-reperfusion and contribute to reperfusion injury. Studies in transgenic animals with altered calpain/calpastatin system subjected to permanent ischemia suggest that calpains are also involved in post-infarction remodelling and heart failure.

Aims: To determine whether delayed oral administration of the calpain inhibitor SNJ-1945 reduces adverse myocardial remodelling and dysfunction following transient coronary occlusion.

Novel targets and future strategies for acute cardioprotection: Position Paper of the European Society of Cardiology Working Group on Cellular Biology of the Heart.

Ischaemic heart disease and the heart failure that often results, remain the leading causes of death and disability in Europe and worldwide. As such, in order to prevent heart failure and improve clinical outcomes in patients presenting with an acute ST-segment elevation myocardial infarction and patients undergoing coronary artery bypass graft surgery, novel therapies are required to protect the heart against the detrimental effects of acute ischaemia/reperfusion injury (IRI). During the last three decades, a wide variety of ischaemic conditioning strategies and pharmacological treatments have been tested in the clinic-however, their translation from experimental to clinical studies for improving patient outcomes has been both challenging and disappointing.

A phase II study of a human anti-PDGFRα monoclonal antibody (olaratumab, IMC-3G3) in previously treated patients with metastatic gastrointestinal stromal tumors.

Background: This study evaluated tumor response to olaratumab (an anti-PDGFRα monoclonal antibody) in previously treated patients with metastatic gastrointestinal stromal tumor (GIST) with or without PDGFRα mutations (cohorts 1 and 2, respectively).

Patients And Methods: Patients received olaratumab 20 mg/kg intravenously every 14 days until disease progression, death, or intolerable toxicity occurred. Outcome measures were 12-week tumor response, progression-free survival (PFS), overall survival (OS), and safety.