Benzodiazepine diazepam regulates cell surface β-adrenergic receptor density in human monocytes.

Downregulation of cell surface β-adrenergic receptors (β-AR) is an important adaptive response that prevents deleterious effects of receptor overstimulation. Various factors including reactive oxygen species cause β-AR downregulation. In this study, we evaluated the effects of ligands of the peripheral benzodiazepine receptor (PBR), a key protein in regulating oxidative stress, on surface density of endogenous β-and β-ARs in highly differentiated cells such as human monocytes, which express both β-AR subtypes.

Renal resistive index in IgA nephropathy and renal scleroderma vasculopathy.

Background: Renal Ultra-Sound (US) and Doppler US provide measurements which reflect changes in renal and systemic haemodynamic. The renal resistive index (RRI), obtained through the Doppler spectrum analysis of renal small arteries, is altered in several pathologic conditions. Glomerulonephritis cause minor RRI changes, while renal scleroderma vasculopathy (RSV) leads to significant RRI modifications.

Cardiovascular Risk and Quality of Life in Autosomal Dominant Polycystic Kidney Disease Patients on Therapy With Tolvaptan: A Pilot Study.

Introduction: Cardiovascular (CV) complications are the most frequent cause of morbidity and mortality in autosomal dominant polycystic kidney disease (ADPKD) patients. In 2017, the Italian Medicines Agency authorised tolvaptan, a vasopressin V2 receptor antagonist, for the treatment of ADPKD, based on the Tolvaptan Phase 3 Efficacy and Safety Study in ADPKD (TEMPO 3: 4), TEMPO 4: 4 and Replicating Evidence of Preserved Renal Function: An Investigation of Tolvaptan Safety and Efficacy (REPRISE) studies.

Aim Of The Study: The aim of the study was to assess the impact of tolvaptan on CV risk and quality of life, evaluated by nutritional, inflammatory, metabolic, instrumental parameters and psychocognitive tests on ADPKD patients.

Role of Alarmins in the Pathogenesis of Systemic Sclerosis.

Systemic sclerosis (SSc) is a rare chronic autoimmune disease associated with significant morbidity and mortality. Two main subsets of SSc are recognized: (i) diffuse cutaneous SSc with rapidly progressive fibrosis of the skin, lungs, and other internal organs; and (ii) limited cutaneous SSc, which is dominated by vascular manifestations, with skin and organ fibrosis generally limited and slowly progressing. In spite of intense investigation, both etiology and pathogenesis of SSc are still unknown.

Oxidative stress in the pathogenesis of systemic scleroderma: An overview.

Systemic sclerosis (SSc) is a rare disorder of the connective tissue characterized by fibrosis of the skin, skeletal muscles and visceral organs. Additional manifestations include activation of the immune system and vascular injury. SSc causes disability and death as the result of end-stage organ failure.

Lung ultrasound in systemic sclerosis: correlation with high-resolution computed tomography, pulmonary function tests and clinical variables of disease.

Interstitial lung disease (ILD) is a hallmark of systemic sclerosis (SSc). Although high-resolution computed tomography (HRCT) is the gold standard to diagnose ILD, recently lung ultrasound (LUS) has emerged in SSc patients as a new promising technique for the ILD evaluation, noninvasive and radiation-free. The aim of this study was to evaluate if there is a correlation between LUS, chest HRCT, pulmonary function tests findings and clinical variables of the disease.

Diesel exhaust particle exposure in vitro impacts T lymphocyte phenotype and function.

Background: Diesel exhaust particles (DEP) are major constituents of ambient air pollution and their adverse health effect is an area of intensive investigations. With respect to the immune system, DEP have attracted significant research attention as a factor that could influence allergic diseases interfering with cytokine production and chemokine expression. With this exception, scant data are available on the impact of DEP on lymphocyte homeostasis.

Relationship between redox status and cell fate in immunity and autoimmunity.

Significance: The signaling function of redox molecules is essential for an efficient and proper execution of a large number of cellular processes, contributing to the maintenance of cell homeostasis. Excessive oxidative stress is considered as playing an important role in the pathogenesis of autoimmune diseases by enhancing inflammation and breaking down the immunological tolerance through protein structural modifications that induce the appearance of neo/cryptic epitopes.

Recent Advances: There is a complex reciprocal relationship between oxidative stress and both apoptosis and autophagy, which is essential to determine cell fate.

Red blood cell alterations in systemic sclerosis: a pilot study.

Aims: The aim of this work was to investigate whether systemic oxidative imbalance that occurs in patients with systemic sclerosis affects red blood cell integrity.

Methods: Reactive oxygen species, intracellular content of total thiols and molecules involved in red blood cell aging (e.g.

Autoantibodies to estrogen receptor α interfere with T lymphocyte homeostasis and are associated with disease activity in systemic lupus erythematosus.

Objective: Estrogens influence many physiologic processes and are also implicated in the development or progression of numerous diseases, including autoimmune disorders. Aberrations of lymphocyte homeostasis that lead to the production of multiple pathogenic autoantibodies, including autoantibodies specific to estrogen receptor (ER), have been detected in the peripheral blood of patients with systemic lupus erythematosus (SLE). This study was undertaken to assess the presence of both anti-ERα and anti-ERβ antibodies in sera from patients with SLE, to analyze the effect of these antibodies on peripheral blood T lymphocyte homeostasis, and to evaluate their role as determinants of disease pathogenesis and progression.

Laser Doppler perfusion imaging in systemic sclerosis impaired response to cold stimulation involves digits and hand dorsum.

Objectives: To assess by Laser Doppler perfusion imaging (LDPI) skin blood perfusion of hands in patients with SSc and primary RP (PRP) at baseline and after cold stimulation (CS). In SSc patients, the associations between skin perfusion and nailfold video capillaroscopy (NVC) patterns were also evaluated.

Methods: Forty patients with SSc, 38 patients with PRP and 32 healthy controls were recruited.

Analyses of T cell phenotype and function reveal an altered T cell homeostasis in systemic sclerosis. Correlations with disease severity and phenotypes.

We investigated in systemic sclerosis (SSc) patients the T cell homeostasis and its relationship with the clinical course of the disease. Distribution of peripheral T cell subsets, thymic output, lymphocyte proliferation and apoptosis were analyzed by flow cytometry or ELISA. Age inappropriate levels of naive CD4(+) T cells and thymic output were observed.

Estrogen receptor profiles in human peripheral blood lymphocytes.

Estrogens are well-known regulators of the immune responses. Most of their effects are mediated by two receptors: estrogen receptor (ER)alpha and ERbeta. Up to date the presence of intracellular ER in human immune cells represents a controversial issue, while their surface membrane expression has scarcely been explored.

Pyrimethamine induces apoptosis of melanoma cells via a caspase and cathepsin double-edged mechanism.

The unresponsiveness of metastatic melanoma to conventional chemotherapeutic and biological agents is largely due to the development of resistance to apoptosis. Pyrimethamine belongs to the group of antifolate drugs, and in addition to antiprotozoan effects, it exerts a strong proapoptotic activity, which we recently characterized in human T lymphocytes. However, no data regarding pyrimethamine anticancer activity are available thus far.

Progressive derangement of the T cell compartment in a case of Evans syndrome.

Background: Evans syndrome (ES) is a rare disorder characterized by combined autoimmune thrombocytopenia and autoimmune hemolytic anemia. Several studies have documented a number of B cell defects, whereas only limited information is currently available about the T cell subset.

Methods: A wide panel of immunological analyses aiming specifically at a quantitative and qualitative evaluation of the T cell compartment was performed in an unusual case of ES.

Unravelling the complexity of T cell abnormalities in common variable immunodeficiency.

We investigated several phenotypic and functional parameters of T cell-mediated immunity in a large series of common variable immunodeficiency (CVID) patients. We demonstrated that the vast majority of CVID patients presented multiple T cell abnormalities intimately related among them, the severity of which was reflected in a parallel loss of CD4+ naive T cells. A strong correlation between the number of CD4+ naive T cells and clinical features was observed, supporting the subgrouping of patients according to their number of naive CD4+ T lymphocytes.

Pyrimethamine (2,4-diamino-5-p-chlorophenyl-6-ethylpyrimidine) induces apoptosis of freshly isolated human T lymphocytes, bypassing CD95/Fas molecule but involving its intrinsic pathway.

Pyrimethamine (2,4-diamino-5-p-chlorophenyl-6-ethyl-pyrimidine), a folic acid antagonist, may exert, in addition to antiprotozoan effects, immunomodulating activities, including induction of peripheral blood lymphocyte apoptosis. However, the molecular mechanisms underlying this proapoptotic activity remain to be elucidated. Here we show that pyrimethamine, used at a pharmacologically relevant concentration, induced per se apoptosis of activated lymphocytes via the activation of the caspase-8- and caspase-10-dependent cascade and subsequent mitochondrial depolarization.

Persistently biased T-cell receptor repertoires in HIV-1-infected combination antiretroviral therapy-treated patients despite sustained suppression of viral replication.

In most HIV-1-infected patients, highly active antiretroviral therapy (HAART) reduces plasma viral load to <50 copies/mL and increases CD4+ T-cell number and function. However, it is still unclear whether alterations of T-cell receptor (TCR) beta-chain variable region (BV) repertoire, tightly related to disease progression, can be fully recovered by long-term treatment with HAART. This study analyzed the evolution of both T-cell subset composition and TCRBV perturbations in chronically HIV-1-infected patients with moderate immunodeficiency during 36 months of HAART.