Tissue factor as a potential coagulative/vascular marker in relapsing-remitting multiple sclerosis.

Objectives: Recent studies supported coagulation involvement in multiple sclerosis, an inflammatory-demyelinating and degenerative disease of the central nervous system. The main objectives of this observational study were to identify the most specific pro-coagulative/vascular factors for multiple sclerosis pathogenesis and to correlate them with brain hemodynamic abnormalities.

Methods: We compared i) serum/plasma levels of complement(C)/coagulation/vascular factors, viral/microbiological assays, fat-soluble vitamins and lymphocyte count among people with multiple sclerosis sampled in a clinical remission (=30; 23F/7M, 40 ± 8.

Homocysteine and Inflammatory Cytokines in the Clinical Assessment of Infection in Venous Leg Ulcers.

Inflammation and biofilm-associated infection are common in chronic venous leg ulcers (VU), causing deep pain and delayed healing. Albeit important, clinical markers and laboratory parameters for identifying and monitoring persistent VU infections are limited. This study analyzed 101 patients with infected (IVU) and noninfected VUs (NVU).

The Impact of Bacterial Biofilms on End-Organ Disease and Mortality in Patients with Hematologic Malignancies Developing a Bloodstream Infection.

Bacterial bloodstream infection (BSI) represents a significant complication in hematologic patients. However, factors leading to BSI and progression to end-organ disease and death are understood only partially. The study analyzes host and microbial risk factors and assesses their impact on BSI development and mortality.

Neutrophil-to-lymphocyte ratio, Factor VIII and Antithrombin III: inflammatory-clotting biomarkers in glioma.

One of the key difficulties in glioma treatment is our limited ability to consistently assess cancer response or progression either by neuroimaging or specific blood biomarkers. An ideal biomarker could be measured through non-invasive methods such as blood-based biomarkers, aiding both early diagnosis and monitoring disease evolution. This is a single-center, case-control, 10-year retrospective, longitudinal study.

Silver Sulfadiazine Eradicates Antibiotic-Tolerant and Biofilms in Patients with Infected Diabetic Foot Ulcers.

Infections are among the most frequent and challenging events in diabetic foot ulcers (DFUs). Pathogenic bacteria growing in biofilms within host tissue are highly tolerant to environmental and chemical agents, including antibiotics. The present study was aimed at assessing the use of silver sulfadiazine (SSD) for wound healing and infection control in 16 patients with DFUs harboring biofilm-growing and .

Coagulation/Complement Activation and Cerebral Hypoperfusion in Relapsing-Remitting Multiple Sclerosis.

Introduction: Multiple sclerosis (MS) is a demyelinating disease of the central nervous system with an underlying immune-mediated and inflammatory pathogenesis. Innate immunity, in addition to the adaptive immune system, plays a relevant role in MS pathogenesis. It represents the immediate non-specific defense against infections through the intrinsic effector mechanism "immunothrombosis" linking inflammation and coagulation.

Naïve/Effector CD4 T cell ratio as a useful predictive marker of immune reconstitution in late presenter HIV patients: A multicenter study.

A significant proportion of HIV-infected patients experiencing a late diagnosis highlights the need to define immunological protocols able to help the clinicians in identifying patients at higher risk for immunological failure. The aim of the study was to evaluate the feasibility of easy cytometric tests in defining the effect of antiretroviral treatment (cART) on immunological homeostasis and in identifying predictive markers of early immune recovery. Chronic HIV infected patients (n = 202) were enrolled in a prospective multicentric study, and their immunological profile was studied before (w0) and after 24 weeks (w24) of antiretroviral treatment (cART) using a standardized flow cytometric panel.

Microbial biofilm correlates with an increased antibiotic tolerance and poor therapeutic outcome in infective endocarditis.

Background: Infective endocarditis (IE) is associated with high rates of mortality. Prolonged treatments with high-dose intravenous antibiotics often fail to eradicate the infection, frequently leading to high-risk surgical intervention. By providing a mechanism of antibiotic tolerance, which escapes conventional antibiotic susceptibility profiling, microbial biofilm represents a key diagnostic and therapeutic challenge for clinicians.

Nucleic Acid Sensing Perturbation: How Aberrant Recognition of Self-Nucleic Acids May Contribute to Autoimmune and Autoinflammatory Diseases.

Bacteria and mammalian cells have developed sophisticated sensing mechanisms to detect and eliminate foreign genetic material or to restrict its expression and replication. Progress has been made in the understanding of these mechanisms, which keep foreign or unwanted nucleic acids in check. The complex of mechanisms involved in RNA and DNA sensing is part of a system which is now appreciated as "immune sensing of nucleic acids" or better "nucleic acid immunity.

The Emerging Role of Microbial Biofilm in Lyme Neuroborreliosis.

Lyme borreliosis (LB) is the most common tick-borne disease caused by the spirochete in North America and or in Europe and Asia, respectively. The infection affects multiple organ systems, including the skin, joints, and the nervous system. Lyme neuroborreliosis (LNB) is the most dangerous manifestation of Lyme disease, occurring in 10-15% of infected individuals.

The clinical Biofilm Ring Test: a promising tool for the clinical assessment of biofilm-producing Candida species.

Candida species are opportunistic pathogens responsible for a variety of diseases, ranging from skin and mucosal lesions to severe systemic, life-threatening infections. Candida albicans accounts for more than 70% of all Candida infections, however, the clinical relevance of other species such as Candida parapsilosis and Candida krusei are being increasingly recognized. Biofilm-producing yeasts cells acquire an increased resistance to antifungal agents, often leading to therapeutic failure and chronic infection.

How Human Papillomavirus Replication and Immune Evasion Strategies Take Advantage of the Host DNA Damage Repair Machinery.

The DNA damage response (DDR) is a complex signalling network activated when DNA is altered by intrinsic or extrinsic agents. DDR plays important roles in genome stability and cell cycle regulation, as well as in tumour transformation. Viruses have evolved successful life cycle strategies in order to ensure a chronic persistence in the host, virtually avoiding systemic sequelae and death.

Activation of DNA Damage Response Induced by the Kaposi's Sarcoma-Associated Herpes Virus.

The human herpes virus 8 (HHV-8), also known as Kaposi sarcoma-associated herpes virus (KSHV), can infect endothelial cells often leading to cell transformation and to the development of tumors, namely Kaposi's sarcoma (KS), primary effusion lymphoma (PEL), and the plasmablastic variant of multicentric Castleman's disease. KSHV is prevalent in areas such as sub-Saharan Africa and the Mediterranean region presenting distinct genotypes, which appear to be associated with differences in disease manifestation, according to geographical areas. In infected cells, KSHV persists in a latent episomal form.

Analysis of the ORFK1 hypervariable regions reveal distinct HHV-8 clustering in Kaposi's sarcoma and non-Kaposi's cases.

Background: Classical Kaposi's Sarcoma (cKS) is a rare vascular tumor, which develops in subjects infected with Human Herpesvirus-8 (HHV-8). Beside the host predisposing factors, viral genetic variants might possibly be related to disease development. The aim of this study was to identify HHV-8 variants in patients with cKS or in HHV-8 infected subjects either asymptomatic or with cKS-unrelated cutaneous lymphoproliferative disorders.

High frequency of antiphospholipid antibodies in relapse of multiple sclerosis: a possible indicator of inflammatory-thrombotic processes.

The exact prevalence and pathogenic role of antiphospholipid antibodies (aPL) in multiple sclerosis (MS) remain unclear. This observational laboratory-blinded study evaluated the rate of aPL positivity in healthy controls and MS patients in different disease phases to recognize their frequency and possible pathogenic meaning. Reactivity for anti-cardiolipin, anti-β2 glycoprotein I, anti-prothrombin, anti-annexin V (IgG and IgM) was studied by enzyme immunoassays in 60 healthy controls and 100 consecutive MS patients [58 relapsing-remitting (RR) patients in remission, 26 RR patients in relapse, and 16 secondary progressive patients].

Assessment of T regulatory cells and expanded profiling of autoantibodies may offer novel biomarkers for the clinical management of systemic sclerosis and undifferentiated connective tissue disease.

In order to identify disease biomarkers for the clinical and therapeutic management of autoimmune diseases such as systemic sclerosis (SSc) and undifferentiated connective tissue disease (UCTD), we have explored the setting of peripheral T regulatory (T reg) cells and assessed an expanded profile of autoantibodies in patients with SSc, including either limited (lcSSc) or diffuse (dcSSc) disease, and in patients presenting with clinical signs and symptoms of UCTD. A large panel of serum antibodies directed towards nuclear, nucleolar, and cytoplasmic antigens, including well-recognized molecules as well as less frequently tested antigens, was assessed in order to determine whether different antibody profiles might be associated with distinct clinical settings. Beside the well-recognized association between lcSSc and anti-centromeric or dcSSC and anti-topoisomerase-I antibodies, we found a significative association between dcSSc and anti-SRP or anti-PL-7/12 antibodies.

Effective therapy with anti-TNF-alpha in patients with psoriatic arthritis is associated with decreased levels of metalloproteinases and angiogenic cytokines in the sera and skin lesions.

Tumor necrosis factor-alpha (TNF-alpha) plays a central role in sustaining the inflammatory process in the skin as well as in the joints of patients with psoriasis and psoriatic arthritis. In fact, biological therapies based on monoclonal antibodies against TNF-alpha have been proven to be effective on both the arthropathy and the cutaneous symptoms of the disease. Among the several effects produced by TNF-alpha on keratinocytes there is the induction of expression of MMP-9, a matrix metalloproteinase (MMP) produced mainly by monocytes and macrophages.

Decreased levels of metalloproteinase-9 and angiogenic factors in skin lesions of patients with psoriatic arthritis after therapy with anti-TNF-alpha.

Background: Inflammation represents an early and key event in the development of both the cutaneous psoriasis and psoriatic arthritis. Compelling evidences indicate that the production of TNF-alpha plays a central role in psoriasis by sustaining the inflammatory process in the skin as well as in the joints. Among the multiple effects produced by TNF-alpha on keratinocytes, the induction of matrix metalloproteinase-9 (MMP-9), a collagenase implicated in joint inflammatory arthritis which acts as an angiogenesis promoting factor, might represent a key mechanism in the pathogenesis of the disease.

Zoledronic-acid-induced circulating level modifications of angiogenic factors, metalloproteinases and proinflammatory cytokines in metastatic breast cancer patients.

Background: To evaluate the modifications of circulating angiogenic factors, metalloproteinases and acute-phase cytokines after the first single zoledronic acid (ZA) intravenous infusion.

Experimental Design: Eighteen consecutive breast cancer patients with bone metastases were evaluated for circulating levels of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), metalloproteinase 1 (MMP-1), metalloproteinase 2 (MMP-2), interleukins 1beta, 6 and 8 (IL-1beta, IL-6, IL-8), interferon gamma, tumor necrosis factor alpha (TNF-alpha) and transforming growth factor beta1 just before and 2 and 7 days after ZA infusion.

Results: The MMP-2 basal value showed a statistically significant decrease 48 h after ZA (p = 0.