Statin-Induced Necrotizing Autoimmune Myopathy: Case Report of a Patient under Chronic Treatment.

Introduction: 3-Hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) inhibitors are widely used worldwide to treat dyslipidaemia and prevent cardiovascular events. Statins can cause a wide variety of muscle injuries ranging from myalgia to severe rhabdomyolysis. In most cases, these symptoms are mild and self-limiting and do not require specific treatment besides drug withdrawal.

Sepsis by in an Elderly Immunocompetent Patient after a Cat Bite.

colonizes animal scratches and bites. This bacterium was described to cause sepsis or endocarditis mainly in immunocompromised patients. We report the case of a 92-year-old woman presenting at the Emergency Department with coma and fever a week after the bite of her cat.

Neutrophil migration towards C5a and CXCL8 is prevented by non-steroidal anti-inflammatory drugs via inhibition of different pathways.

Background And Purpose: Non-steroidal anti-inflammatory drugs (NSAIDs) have been shown to induce PG-independent anti-inflammatory actions. Here, we investigated the role of three different NSAIDs (naproxen, ibuprofen and oxaprozin) on neutrophil responses to CXCL8 and C5a.

Experimental Approach: Human neutrophils were isolated from healthy volunteers by dextran and Ficoll-Hypaque density gradients.

Syndrome of inappropriate antidiuretic hormone secretion and Ibuprofen, a rare association to be considered: role of tolvaptan.

The association between the syndrome of inappropriate antidiuretic hormone secretion (SIADH) and the use of nonsteroidal anti-inflammatory drugs (NSAIDs) is rare and has never been treated with an arginine vasopressin receptor antagonist. We report a unique case of SIADH associated with ibuprofen use and successfully treated with tolvaptan. A 76-year-old man came to our observation because of lumbar pain and epigastric discomfort.

Exocytosis of azurophil and arginase 1-containing granules by activated polymorphonuclear neutrophils is required to inhibit T lymphocyte proliferation.

ARG1, expressed by human PMNs, inhibits T cell proliferation by depleting extracellular L-arginine. Here, we report that ARG1, released from gelatinase granules by PMNs, is inactive at physiological pH unless activated by factor(s) stored in azurophil granules. Whereas ARG1 exocytosis was induced by TNF-α or ionomycin, only the latter mediated the release of both granules, resulting in extracellular ARG enzyme activity at physiological pH.

Acipimox reduces circulating levels of insulin and associated neutrophilic inflammation in metabolic syndrome.

Metabolic syndrome is a proatherosclerotic condition clustering cardiovascular risk factors, including glucose and lipid profile alterations. The pathophysiological mechanisms favoring atherosclerotic inflammation in the metabolic syndrome remain elusive. Here, we investigated the potential role of the antilipolytic drug acipimox on neutrophil- and monocyte-mediated inflammation in the metabolic syndrome.

Systemic and intraplaque mediators of inflammation are increased in patients symptomatic for ischemic stroke.

Background And Purpose: The concept of "vulnerable plaque" has been extended to the more recent definition of the "cardiovascular vulnerable patient," in which "intraplaque" and "systemic" factors contribute to the cumulative risk of acute cardiovascular events. Thus, we investigated the possible role of systemic and intraplaque inflammation in patients asymptomatic versus symptomatic for ischemic stroke.

Methods: Regions upstream and downstream the blood flow were isolated from internal carotid plaques of patients asymptomatic (n=63) or symptomatic (n=18) for ischemic stroke.

Coronary artery calcification and cardiovascular risk: the role of RANKL/OPG signalling.

Background: Coronary artery disease (CAD) represents the most relevant cause of death and morbidity in the adult population of developed and developing countries. During the last decades, a strong research effort has been performed to identify more selective markers and better assess the cardiovascular risk in both primary and secondary prevention.

Materials And Methods: This review updates current knowledge regarding the pathophysiological relevance as possible markers of coronary calcification of the receptor activator of nuclear factor-kappa ligand (RANKL)/osteoprotegerin (OPG) system.

CX3CR1 is expressed by human B lymphocytes and mediates [corrected] CX3CL1 driven chemotaxis of tonsil centrocytes.

Background: Fractalkine/CX(3)CL1, a surface chemokine, binds to CX(3)CR1 expressed by different lymphocyte subsets. Since CX(3)CL1 has been detected in the germinal centres of secondary lymphoid tissue, in this study we have investigated CX(3)CR1 expression and function in human naïve, germinal centre and memory B cells isolated from tonsil or peripheral blood.

Methodology/principal Findings: We demonstrate unambiguously that highly purified human B cells from tonsil and peripheral blood expressed CX(3)CR1 at mRNA and protein levels as assessed by quantitative PCR, flow cytometry and competition binding assays.

sHLA-I contaminating molecules as novel mechanism of ex vivo/in vitro transcriptional and posttranscriptional modulation of transforming growth factor-beta in CD8+ T lymphocytes and neutrophils after intravenous immunoglobulin treatment.

Background: Numerous mechanisms have been proposed to explain the beneficial action of intravenous immune globulin (IVIG) in autoimmune and systemic inflammatory disorders. Among others' data, an in vitro increase of intracellular TGF-beta expression when culturing CD4+ T lymphocytes in the presence of IVIG has been reported. As IVIG infusion involves administration of soluble contaminants likewise all hemoderivative preparations, we hypothesized that, besides several other immunomodulatory proposed mechanisms, the clinical effects of IVIG therapy might be, at least partly, due to contaminating soluble HLA Class I (sHLA-I) molecules capable to exert pleiotropic immunomodulatory effects among which TGF-beta(1) modulation.

Antiproliferative and proapoptotic activities of a new class of pyrazole derivatives in HL-60 cells.

A series of N-substituted pyrazole derivatives have been synthesized and tested for their anticancer effect on the HL-60 leukaemia cell line. Four were active both in cell-growth inhibition and in inducing apoptosis. The inhibition of cell growth mainly reflects a compound-induced reduction in the number of cells in phases from S to M, whereas the induction of apoptosis involves inhibition of expression of Bcl-2 and enhanced expression of Bax with consequent reduced activation of the proapoptotic caspase 3.

Oxaprozin-induced apoptosis on CD40 ligand-treated human primary monocytes is associated with the modulation of defined intracellular pathways.

The modulation of CD40L activity might represent a promising therapeutic target to reduce monocyte inflammatory functions in chronic diseases, such as rheumatoid arthritis. In the present study, we investigated the possible influence of nonsteroidal anti-inflammatory drugs (NSAIDs) on CD40L-induced monocyte survival. Monocytes were isolated from buffy coats by using Ficoll-Percoll gradients.

Intestinal radiation-induced stricture favours small bowel obstruction by phytobezoar: report of a case.

Bezoars represent the fifth most frequent cause of acute small bowel obstruction. Phytobezoar is the most common type of bezoar. It is a concretion of undigestible fibers derived from ingested vegetables and fruits.

Delayed apoptosis of human monocytes exposed to immune complexes is reversed by oxaprozin: role of the Akt/IkappaB kinase/nuclear factor kappaB pathway.

Background And Purpose: Monocytes-macrophages play a key role in the initiation and persistence of inflammatory reactions. Consequently, these cells represent an attractive therapeutic target for switching off overwhelming inflammatory responses. Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most common drugs for the symptomatic treatment of rheumatic diseases.

Tumor necrosis factor-alpha (TNF-alpha) induces integrin CD11b/CD18 (Mac-1) up-regulation and migration to the CC chemokine CCL3 (MIP-1alpha) on human neutrophils through defined signalling pathways.

Strong evidence suggests that neutrophils may play an active role in acute and chronic inflammatory disorders, such as rheumatoid arthritis and atherosclerosis. Given the role of pro-inflammatory cytokine TNF-alpha in these inflammatory processes, we planned the present study to investigate the effect of short term incubation with TNF-alpha on neutrophil migration to CCL3, a chemokine produced in inflammatory sites and normally devoid of neutrophil chemotactic properties. We found that TNF-alpha primed neutrophils for migration to CCL3 via CCR5.

Are there any differences among non-steroidal anti-inflammatory drugs? Focus on nimesulide.

Although the efficacy of non-steroidal anti-inflammatory drugs (NSAIDs) as anti-inflammatory, analgesic and antipyretic agents is well established, there is still an open question as to whether their different pharmacokinetic and pharmacodynamic characteristics do have a different clinical impact in treating rheumatology patients. The mechanism related to the anti-inflammatory activity of these drugs is mainly related to the inhibition of the cyclo-oxygenase (COX)-2 isoform, whereas inhibition of COX-1 is associated with the side effects of these drugs. However, some NSAIDs exert their anti-inflammatory and analgesic action by additional mechanisms.

Human mesenchymal stem cells inhibit neutrophil apoptosis: a model for neutrophil preservation in the bone marrow niche.

Mesenchymal stem cells (MSC) establish close interactions with bone marrow sinusoids in a putative perivascular niche. These vessels contain a large storage pool of mature nonproliferating neutrophils. Here, we have investigated the effects of human bone marrow MSC on neutrophil survival and effector functions.

Nonleukoreduced red blood cell transfusion induces a sustained inhibition of neutrophil chemotaxis by stimulating in vivo production of transforming growth factor-beta1 by neutrophils: role of the immunoglobulinlike transcript 1, sFasL, and sHLA-I.

Background: Red blood cell (RBC) transfusion has been linked to increased susceptibility to infections in critically ill patients and to augmented incidence of postoperative infections. The mechanisms by which transfusions can induce immunosuppression are only partially defined. Recently, it has been demonstrated that RBC supernatants inhibit neutrophil migration.

Synthesis and biological evaluation of N-pyrazolyl-N'-alkyl/benzyl/phenylureas: a new class of potent inhibitors of interleukin 8-induced neutrophil chemotaxis.

Neutrophils chemotaxis is a complex multistep process that, if upregulated, causes acute inflammation and a number of autoimmune diseases. We report here the synthesis of a new N-(4-substituted)pyrazolyl-N'-alkyl/benzyl/phenylureas that are potent inhibitors of interleukin-8 (IL8)-induced neutrophil chemotaxis. The first series of compounds, obtained by functionalization with a urea moiety of the 5-amino-1-(2-hydroxy-2-phenylethyl)-1H-pyrazole-4-carboxylic acid ethyl ester 3, blocked the IL8-induced neutrophil chemotaxis, while they did not block N-formylmethionylleucylphenylalanine-mediated chemotaxis.

Nephrotic syndrome in a patient with IgM myeloma with associated neutrophilia.

An unusual case having IgM monoclonal gammopathy with clinical and pathologic features of multiple myeloma (MM) in association with neutrophilia and nephrotic syndrome is reported. The patient showed lytic bone lesions, decreased IgG and IgA levels, Bence-Jones proteinuria, nephrotic proteinuria with edema, and histological plasma cell infiltration typical of MM. Moreover, mature neutrophilic leukocytosis, hepatomegaly, high leukocyte alkaline phosphatase score (LAP), absence of Philadelphia (Ph) chromosome and bcr gene rearrangement were also evidenced, all these features representing findings typical of the recently described plasma cell dyscrasia-associated neutrophilia.

Immune complexes induce monocyte survival through defined intracellular pathways.

Monocytes recruitment and survival at sites of inflammation are determinant for the persistence of inflammatory reactions. Immune-complexes (ICs), whose tissue deposition is involved in a variety of autoimmune diseases, activate monocytes through the interaction with Fcgamma-receptor triggering the secretion of several inflammatory modulators and favoring their tissue accumulation by inhibiting the apoptosis. To elucidate the intracellular pathways governing this process, on the basis of our previous findings regarding the dose-dependent inhibition of apoptosis in IC-activated monocytes, we have investigated the role of PI3K/Akt pathway, MAP kinases, nuclear factor-kappaB (NF-kappaB), and caspase 3, 8, and 9.

Insulin primes human neutrophils for CCL3-induced migration: crucial role for JNK 1/2.

The present article shows that a short-term exposure of purified human neutrophils to recombinant insulin conferred on these cells both the ability to migrate and the capacity to mobilize [Ca2+]i in response to CCL3, a chemokine per se ineffective with native neutrophils. Furthermore, the effects of recombinant insulin were reproduced by short-term incubation with sera from adult patients with metabolic syndrome, known to be characterized by a hyperinsulinemic state. A strict linear correlation (P<0.