The Emerging Role of Microbial Biofilm in Lyme Neuroborreliosis

Lyme borreliosis (LB) is the most common tick-borne disease caused by the spirochete Borrelia burgdorferi in North America and Borrelia afzelii or Borrelia garinii 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. During the course of the infection, bacteria migrate through the host tissues altering the coagulation and fibrinolysis pathways and the immune response, reaching the central nervous system (CNS) within 2 weeks after the bite of an infected tick. The early treatment with oral antimicrobials is effective in the majority of patients with LNB. Nevertheless, persistent forms of LNB are relatively common, despite targeted antibiotic therapy. It has been observed that the antibiotic resistance and the reoccurrence of Lyme disease are associated with biofilm-like aggregates in B. burgdorferi, B. afzelii, and B. garinii, both in vitro and in vivo, allowing Borrelia spp. to resist to adverse environmental conditions. Indeed, the increased tolerance to antibiotics described in the persisting forms of Borrelia spp., is strongly reminiscent of biofilm growing bacteria, suggesting a possible role of biofilm aggregates in the development of the different manifestations of Lyme disease including LNB

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

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-α 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-α 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. Aims of the present study were to investigate a) the role of MMP-9 in the development of psoriasis by assessing the presence of MMP-9 in lesional skin and in sera of psoriatic patients; b) the association of MMP-9 with the activity of the disease; c) the relationship between MMP-9 and TNF-α production. METHODS: Eleven psoriatic patients, clinically presenting joint symptoms associated to the cutaneous disease, were included in a therapeutic protocol based on the administration of anti-TNF-α monoclonal antibody (Infliximab). Sera and skin biopsies were collected before treatment and after 6 weeks of therapy. Tissues were kept in short term cultures and production soluble mediators such as TNF-α, MMP-9, MMP-2, VEGF and E-Selectin, which include angiogenic molecules associated to the development of plaque psoriasis, were measured in the culture supernatants by immunoenzymatic assays (ng/ml or pg/ml per mg of tissue). MMP-9 concentrations were also measured in the sera. The cutaneous activity of disease was evaluated by the Psoriasis Area and Severity Index (PASI). RESULTS: Clinical and laboratory assessment indicated that all but one patients had a significant improvement of the PASI score after three months of therapy. The clinical amelioration was associated to a significant decrease of MMP-9 (P = 0.017), TNF-α (P = 0.005) and E-selectin (P = 0.018) levels, spontaneously released by lesional biopsies before and after therapy. In addition, significant correlations were found between the PASI measurements and TNF-α (r(2 )= 0.33, P = 0.005), MMP-9 (r(2 )= 0.25, P = 0.017), E-selectin (r(2 )= 0.24, P = 0.018) production. MMP-9 levels were significantly correlated with those of TNF-α (r(2 )= 0.30, P = 0.008). A significant decrease of MMP-9 in the sera, associated to the clinical improvement was also found. CONCLUSION: Our findings show the existence of a direct relationship between MMP-9 and TNF-α production strongly suggesting that MMP-9 may play a key role in the skin inflammatory process in psoriasis

Human Herpesvirus 8 Infection in Patients With Cutaneous Lymphoproliferative Diseases

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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. In addition, two distinct groups emerged on the basis of anti-RNP or anti-PM-Scl 75/100 antibody production among UCTD patients. The levels of T reg cells were significantly lower in patients with SSc as compared to patients with UCTD or to healthy controls; in patients with lcSSc, T reg cells were inversely correlated to disease duration, suggesting that their levels may represent a marker of disease progression

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. Conventional methods such as crystal violet (CV) and tetrazolium (XTT) reduction assay, developed to evaluate biofilm formation in Candida species are usually time-consuming, present a high intra- and inter-assay variability of the results and are therefore hardly applicable to routine diagnostics. This study describes an in-vitro assay developed for the measurement of biofilm formation in Candida species based on the clinical Biofilm Ring Test ®(cBRT). We found a significant concordance between the cBRT and both CV (k = 0.74) and XTT (k = 0.62), respectively. Nevertheless, the cBRT resulted more reliable and reproducible than CV and XTT, requiring a minimal sample manipulation and allowing a high throughput assessment, directly on viable cells. The results indicate that the cBRT may provide a suitable, cost-effective technique for routine biofilm testing in clinical microbiology

Energy policy implications of carbon pricing scenarios for the Brazilian NDC implementation

International audienceThis study assesses the expansion of the Brazilian energy system across three GHG emissions pathways simulatingthe achievement of the Brazilian Nationally Determined Contribution. In the Reference scenario, the NDC isachieved through command-and-control policies. We then compare this pathway to an Emissions Pricing Scenario (EPS), which simulates a carbon pricing scheme. The Sensitive Fuels Exemption Scenario (SFE) is similar tothe latter, but gasoline, diesel and liquefied petroleum gas are exempted from pricing, strengthening politicalbuy-in to the mechanism.An integrated modelling approach combines bottom-up models representing energy demand and supply and amacroeconomic framework to ensure consistency across them. The adoption of carbon pricing schemes enablesthe use of a large potential of offsets (from the restoration of native vegetation) at a limited cost. This allowsmeeting NDC targets with bounded use of expensive mitigation actions comprised in command-and-control toolsin the reference scenario. This study shows that a carbon pricing policy can increase the effectiveness of meetingclimate commitments in Brazil, reducing GDP losses against business-as-usual trends. However, the mechanism’sscope and sectoral coverage are key to ensure that decarbonisation is pursued in all economic sectors and in linewith climate targets beyond the NDC horizon