Excitatory amino acid transporter 1 supports adult hippocampal neural stem cell self-renewal.

Within the adult mammalian dentate gyrus (DG) of the hippocampus, glutamate stimulates neural stem cell (NSC) self-renewing proliferation, providing a link between adult neurogenesis and local circuit activity. Here, we show that glutamate-induced self-renewal of adult DG NSCs requires glutamate transport via excitatory amino acid transporter 1 (EAAT1) to stimulate lipogenesis. Loss of EAAT1 prevented glutamate-induced self-renewing proliferation of NSCs and , with little role evident for canonical glutamate receptors.

Effects of the Italian Law on Patient Safety and Health Professional Responsibilities Five Years after Its Approval by the Italian Parliament.

The application of the Italian law No. 24/2017, which focused on patient safety and medical liability, in the Italian National Health Service has been evaluated by a survey conducted five years after the promulgation of the law. The law required the establishment of healthcare risk management and patient safety centers in all Italian regions and the appointment of a Clinical Risk Manager (CRM) in all Italian public and private healthcare facilities.

Restoring tripartite glutamatergic synapses: A potential therapy for mood and cognitive deficits in Gulf War illness.

Gulf War illness is associated with a combination of exposure to war-related chemical agents and traumatic stress. Currently, there are no effective treatments, and the pathophysiology remains elusive. Neurological problems are among the most commonly reported symptoms.

Activation of alpha7 nicotinic and NMDA receptors is necessary for performance in a working memory task.

Rationale: Working memory deficits are present in schizophrenia (SZ) but remain insufficiently resolved by medications. Similar cognitive dysfunctions can be produced acutely in animals by elevating brain levels of kynurenic acid (KYNA). KYNA's effects may reflect interference with the function of both the α7 nicotinic acetylcholine receptor (α7nAChR) and the glycineB site of the NMDA receptor.

Adolescent cannabis exposure increases heroin reinforcement in rats genetically vulnerable to addiction.

On the basis of epidemiological studies it has been proposed that cannabis use plays a causal role in the abuse of highly addictive drugs (Gateway Hypothesis). However, epidemiological studies are intrinsically unable to provide evidence of causality. Experimental studies can provide this evidence but they are feasible only in animal models and to date such evidence is lacking.

Subclinical Atherosclerosis in Primary Sjögren's Syndrome: Does Inflammation Matter?

Sjögren's syndrome (SS) is a systemic autoimmune disease mainly characterized by inflammatory involvement of exocrine gland. Atherosclerosis is a complex process leading to plaque formation in arterial wall with subsequent cardiovascular (CV) events. Recently, numerous studies demonstrated that SS patients bear an increased CV risk.

Targeting Inflammation to Prevent Cardiovascular Disease in Chronic Rheumatic Diseases: Myth or Reality?

Evidence for increased risk of cardiovascular morbidity and mortality in chronic inflammatory rheumatic diseases has accumulated during the last years. Traditional cardiovascular risk factors contribute in part to the excess of cardiovascular risk in these patients and several mechanisms, including precocious acceleration of subclinical atherosclerotic damage, inflammation, and immune system deregulation factors, have been demonstrated to strictly interplay in the induction and progression of atherosclerosis. In this setting, chronic inflammation is a cornerstone of rheumatic disease pathogenesis and exerts also a pivotal role in all stages of atherosclerotic damage.

One year in review 2018: idiopathic inflammatory myopathies.

Idiopathic inflammatory myopathies (IIMs) are a group of chronic autoimmune systemic diseases affecting the skeletal muscle and other organs. IIMs are also a complex group of diseases, in some cases, difficult to manage. Literature on IIMs has been growing fairly rapidly and keeping up-to-date on such a topic is of utmost importance for any rheumatologist who looks after IIM patients.

Discrepancy between subjective symptoms, objective measures and disease activity indexes: the lesson of primary Sjögren's syndrome.

Mucosal dryness is a key clinical feature in primary Sjögren's syndrome (pSS) and its assessment relies on both objective measurement of residual secretion and subjective symptoms reported by patients. However, while the objective assessment and grading of glandular dysfunction can be easily performed, the spectrum of clinical symptoms encompassed by the terms 'dry eye' and 'dry mouth' is wide and heterogeneous. Therefore, patient reported outcomes (PROs) for dryness in pSS poorly correlate with the amount of glandular secretion.

The prevalence and relevance of traditional cardiovascular risk factors in primary Sjögren's syndrome.

Accelerated atherosclerosis is a distinct feature of some inflammatory and autoimmune disorders and several specific autoimmune mechanisms and persistent inflammation have been identified to exert a pivotal role in precocious atherosclerotic damage in these disorders. Although increased atherosclerotic risk has been well established in some rheumatic autoimmune systemic diseases, such as systemic lupus erythematosus and rheumatoid arthritis, reliable data regarding the prevalence and pathogenetic mechanisms associated with increased atherosclerotic damage in primary Sjögren's syndrome are scarse. Indeed, primary Sjögren's syndrome is an autoimmune disorder characterised by chronic inflammation and autoimmune dysregulation that shares many pathogenic mechanisms and clinical features with systemic lupus erythematosus and rheumatoid arthitis.

One year in review 2017: idiopathic inflammatory myopathies.

Every year new concepts about pathogenesis, serology, diagnosis and treatment in inflammatory myopathies (IIMs) have been provided. The purpose of this manuscript is to summarise the most relevant literature contributions published over the last year about these complex and rare diseases.

Novel Therapeutic Strategies in Primary Sjögren's Syndrome.

Primary Sjögren's syndrome (pSS) is a chronic autoimmune disease mainly affecting exocrine glands. However, a subgroup of patients experiences extraglandular manifestations which worsens disease prognosis. To date evidence based guidelines for the management of pSS are lacking, hence the therapeutic approach is mainly based on expert opinion and data from other connective tissue diseases.

Prevalence and significance of anti-saccharomyces cerevisiae antibodies in primary Sjögren's syndrome.

Objectives: Saccharomyces cerevisiae is a common yeast used in the food industry. IgG and IgA antibodies against the phosphopeptidomannan of the S. cerevisiae cell wall (ASCA) are a well known marker of disease severity in Crohn's disease.

Insulin-Like Growth Factor Binding Protein 6 in Rheumatoid Arthritis: A Possible Novel Chemotactic Factor?

Objectives: Immune cell migration from the bloodstream to target tissues is a hallmark of rheumatoid arthritis (RA) pathogenesis. The role of chemoattractants, mainly chemokines, and their possible targeting for therapeutic purposes have been under intense investigation over the last few years but the results were not as satisfactory as expected. The insulin-like growth factor binding protein 6 (IGFBP6), a direct inhibitor of insulin-like growth factor (IGF)-II, also exerts IGF-independent effects including tumor cell migration .

Prenatal kynurenine exposure in rats: age-dependent changes in NMDA receptor expression and conditioned fear responding.

Rationale: Levels of kynurenic acid (KYNA), an endogenous negative modulator of alpha 7 nicotinic acetylcholine receptors (α7nAChRs) and antagonist at glutamatergic N-methyl-D-aspartate receptors (NMDARs), are elevated in the brain of patients with schizophrenia (SZ). In rats, dietary exposure to KYNA's immediate precursor kynurenine during the last week of gestation produces neurochemical and cognitive deficits in adulthood that resemble those seen in patients with SZ.

Objectives: The present experiments examined whether prenatal kynurenine exposure results in age-dependent changes in the kynurenine pathway (KP), expression of selected receptors, and cognitive function.

Caffeine, a common active adulterant of cocaine, enhances the reinforcing effect of cocaine and its motivational value.

Rationale: Caffeine is one of the psychoactive substances most widely used as an adulterant in illicit drugs, such as cocaine. Animal studies have demonstrated that caffeine is able to potentiate several cocaine actions, although the enhancement of the cocaine reinforcing property by caffeine is less reported, and the results depend on the paradigms and experimental protocols used.

Objectives: We examined the ability of caffeine to enhance the motivational and rewarding properties of cocaine using an intravenous self-administration paradigm in rats.

One year in review 2016: novelties in the treatment of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic disease characterised by inflammation of the synovial tissue in joints, which can lead to joint destruction. The primary goal of the treatment is to control pain and inflammation, reduce joint damage and disability, and maintain or improve physical function and quality of life. The present review is aimed at providing a critical analysis of the recent literature on the novelties in the treatment of RA, with a particular focus on the most relevant studies published over the last year.

Altered immunoregulation in rheumatoid arthritis: the role of regulatory T cells and proinflammatory Th17 cells and therapeutic implications.

In recent years several studies investigated the role of T lymphocyte subpopulations in the pathogenesis of rheumatoid arthritis (RA). Pathogenic Th17 cells mediate pannus growth, osteoclastogenesis, and synovial neoangiogenesis; hence they are key players in the development of the disease. On the other hand, regulatory T (Treg) cells are a T cell subset whose peculiar function is to suppress autoreactive lymphocytes.

One year in review 2015: Sjögren's syndrome.

Primary Sjögren's syndrome (pSS) is a chronic autoimmune disease mainly characterised by the inflammation of exocrine glands; however, a broad spectrum of systemic manifestations may characterise the disease. Recently, pSS has been the object of considerable immunologic and clinical research which has led to significant advances in the diagnosis, prognostic assessment and management of the disease. Herewith, we provide a critical digest of the recent literature on this topic.

Cardiovascular disease in systemic sclerosis.

Cardiovascular (CV) system involvement is a frequent complication of autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). It still remains unclear if a premature atherosclerosis (ATS) occurs even in systemic sclerosis (SSc). Although microvascular disease is a hallmark of SSc, in the last few years a number of studies highlighted a higher prevalence of macrovascular disease in SSc patients in comparison to healthy individuals and these data have been correlated with a poorer prognosis.

Impairment of acquisition of intravenous cocaine self-administration by RNA-interference of dopamine D1-receptors in the nucleus accumbens shell.

Microdialysis during i.v. drug self-administration (SA) have implicated nucleus accumbens (NAc) shell DA in cocaine and heroin reinforcement.

Endocannabinoid 2-Arachidonoylglycerol Self-Administration by Sprague-Dawley Rats and Stimulation of in vivo Dopamine Transmission in the Nucleus Accumbens Shell.

2-Arachidonoylglycerol (2-AG) is the most potent endogenous ligand of brain cannabinoid CB1 receptors and is synthesized on demand from 2-arachidonate-containing phosphoinositides by the action of diacylglycerol lipase in response to increased intracellular calcium. Several studies indicate that the endocannabinoid (eCB) system is involved in the mechanism of reward and that diverse drugs of abuse increase brain eCB levels. In addition, eCB are self-administered (SA) by squirrel monkeys, and anandamide increases nucleus accumbens (NAc) shell dopamine (DA) in rats.

A systematic microdialysis study of dopamine transmission in the accumbens shell/core and prefrontal cortex after acute antipsychotics.

Rationale: The only systematic in vivo studies comparing antipsychotic (AP) effects on nucleus accumbens (NAc) shell and core dopamine (DA) transmission are voltammetric studies performed in pargyline-pretreated, halothane-anaesthetized rats. Studies in freely moving rats not pretreated with pargyline are not available. This study was intended to fill this gap by the use of in vivo microdialysis in freely moving rats.

Balance between regulatory T and Th17 cells in systemic lupus erythematosus: the old and the new.

Pathogenic mechanisms underlying the development of systemic lupus erythematosus (SLE) are very complex and not yet entirely clarified. However, the pivotal role of T lymphocytes in the induction and perpetuation of aberrant immune response is well established. Among T cells, IL-17 producing T helper (Th17) cells and regulatory T (Treg) cells represent an intriguing issue to be addressed in SLE pathogenesis, since an imbalance between the two subsets has been observed in the course of the disease.