Laminin-6 and Laminin-5 Are Recognized by Autoantibodies in a Subset of Cicatricial Pemphigoid

We characterized basement membrane zone (BMZ) autoantigens targeted by autoantibodies (AAb) from patients with cicatricial pemphigoid. Serum from a patient with severe oral cicatricial pemphigoid contained IgG anti-BMZ AAb. The AAb labeled a lower BMZ component on salt-split skin and localized to the lower lamina lucida/lamina densa by direct and indirect immunoelectron microscopy (HEM) but did not label blood vessels. The AAb did not react with EHS laminin-1 and type IV collagen, pepsinized human type IV collagen, recombinant entactin, or NC1 domain of type VII collagen by dot blotting and western blotting. We focused our studies on the laminin family, as laminin-5 was identified as an autoantigen in cicatricial pemphigoid. Culture-conditioned media from normal keratinocytes (containing laminin-6 and laminin-5) and JEB keratinocytes (containing laminin-6 but not laminin-5) were studied by western blotting. Under nonreducing conditions, the patient's AAb recognized a 600-kDa protein (laminin-6) intensely and a 400-kDa protein (laminin-5) weakly in normal keratinocyte medium even though abundant laminin-5 was present. In JEB keratinocyte medium, however, the 600-kDa protein (laminin-6) alone was recognized by the patient's AAb. The AAb also immunolabeled BMZ of JEB skin that lacked laminin-5. The AAb from this patient and two other patients with anti-laminin-5 cicatricial pemphigoid immunoprecipitated both laminin-6 an4 laminin-5. Taken together, the results of IEM, non-reducing western blotting, immunoprecipitation, and JEB skin BMZ immunolabeling indicate that laminin-6, as well as laminin-5, is identified by the AAb from a subset of cicatricial pemphigoid patients. We propose the name “anti-laminin cicatricial pemphigoid” for this subset

Produção de biodiesel e geração de energia elétrica a partir de óleo de mamona em Quixeramobim, CE.

Introdução; Fase agrícola - produção de mamona; Fase industria l- extração de óleo e transesterificação; Fase final - geração de energia elétrica; Considerações finais.bitstream/CNPA/17471/1/DOC136.pd

Continuous Subcutaneous Insulin Infusion in Patients With Type 2 Diabetes A Cohort Study to Establish the Relationship Between Glucose Control and Plasma Oxidized Low Density Lipoprotein

Background: Oxidative stress is a detrimental feature of diabetes implicated in the progression of the disease and its complications. The relationship between insulin therapy and oxidative stress is complex. This study tested the hypothesis that improved glucose control, rather than insulin dose, is central to reduced oxidative stress in patients with type 2 diabetes following continuous subcutaneous insulin infusion (CSII). Methods: In this 16-week, multicenter study, 54 CSII-naïve patients with type 2 diabetes (age 57 ± 10 years, HbA1c 69 ± 15 mmol/mol [8.5 ± 1.4%], diabetes duration 13 ± 6 years) treated with either oral antidiabetic agents (OAD) alone (n = 17), basal insulin ± OAD (n = 17), or multiple daily injections (MDI) ± OAD (n = 20) were the evaluable group. Diabetes medications except metformin were discontinued, and 16 weeks of CSII was initiated. Insulin dose was titrated to achieve optimal glycemic control. A plasma marker of oxidative stress relevant to cardiovascular disease (oxidized low density lipoprotein [ox-LDL]) was assessed at baseline and week 16. Results: CSII improved glycemic control (HbA1c −13 ± 2 mmol/mol [−1.2 ± 0.2%]; fasting glucose −36.6 ± 8.4 mg/dL; mean glucose excursion −23.2 ± 6.5 mg/dL, mean ± SE; all P .05), but was significantly more pronounced in patients on statins (P = .019). The effect of CSII was more closely correlated to improvements in glucose excursion (P = .013) than to insulin dose (P > .05) or reduction in HbA1c (P > .05). Conclusions: CSII induces depression of plasma ox-LDL associated with change in glucose control, rather than with change in insulin dose. The effect is augmented in patients receiving statins

Retroperitoneal Castleman's tumor and paraneoplastic pemphigus: report of a case and review of the literature

BACKGROUND: Castleman's disease is a rare lymphoproliferative syndrome. Its etiology and pathogenesis are unclear. The disease can be occasionally associated with a paraneoplastic pemphigus (PNP), an autoimmune mucocutaneous disorder commonly seen in neoplasms of lymphocytic origin. CASE PRESENTATION: We present a case of a 63-year old male patient who was referred for surgical treatment of a lately diagnosed retroperitoneal pelvic mass. The patient had been already treated for two years due to progressive diffuse cutaneous lesions histologically consistent with lichen ruber verucosus and pemphigus vulgaris. Intraoperatively a highly vascularized solid mass occupying the small pelvis was resected after meticulous vascular ligation and hemostasis. After surgery and following immunosuppressive treatment a clear remission of the skin lesions was observed. CONCLUSION: Castleman's tumor should be always suspected when a retroperitoneal mass is combined with PNP. In a review of the literature we found 37 additional cases. Complete surgical resection of the tumor can be curative in most of the cases

The Protease Inhibitor Alpha-2-Macroglobuline-Like-1 Is the p170 Antigen Recognized by Paraneoplastic Pemphigus Autoantibodies in Human

Paraneoplastic pemphigus (PNP) is a devastating autoimmune blistering disease, involving mucocutaneous and internal organs, and associated with underlying neoplasms. PNP is characterized by the production of autoantibodies targeting proteins of the plakin and cadherin families involved in maintenance of cell architecture and tissue cohesion. Nevertheless, the identity of an antigen of Mr 170,000 (p170), thought to be critical in PNP pathogenesis, has remained unknown

Klimafolgenabschätzungen in der Wasserwirtschaft und deren Nutzen für die Praxis

KlimafolgenClimate ImpactsDer globale Klimawandel kann regional unterschiedliche Auswirkungen haben. Während sich die wissenschaftliche Forschung vor allem mit der Analyse der Daten beschäftigt, ist die fachliche Praxis darum bemüht, die Ergebnisse zu interpretieren und Handlungsempfehlungen daraus abzuleiten. Im Zuge des Projektes KliBiW (Globaler Klimawandel – Wasserwirtschaftliche Folgenabschätzung für das Binnenland) wurden die Auswirkungen des Klimawandels auf die Hochwasser- und Niedrigwasserverhältnisse in Niedersachsen untersucht. Hierzu wurden die Daten von zwei regionalen Klimamodellen (WETTREG2006 und REMO), beide angetrieben durch das Globalmodell ECHAM5/MPI-OM, räumlich interpoliert und die Niederschläge zum Teil zeitlich disaggregiert, um hoch aufgelöste Klimainformationen bereitzuhalten. Anschließend erfolgte die Kopplung mit einem hydrologischen Modellsystem (PANTA RHEI), das bereits in der Hochwasservorhersagezentrale des NLWKN im Einsatz ist. Über Langzeitsimulationen wurden zukünftige Veränderungen in den Abflussverhältnissen räumlich und zeitlich differenziert für das Aller-Leine Gebiet identifiziert. Als Betrachtungszeiträume dienten eine nahe Zukunftsphase (2021 – 2050) und eine ferne Zukunftsphase (2071 – 2100). Die Veränderungen verschiedener hydrologischer Hoch- und Niedrigwasser-Kenngrößen wurden gegenüber einem Kontrollzeitraum (1971 – 2000) aufgezeigt. Die Auswertungen an 8 Pegeln in Einzugsgebieten >1.000 km² auf Tageswertbasis und an 6 Pegeln in Einzugsgebieten <1.000 km² auf Stundenwertbasis zeigten, dass sich die Hochwassersituation zukünftig verschärfen kann. Während kleinere Hochwässer häufiger auftreten können, nehmen die Scheitelabflüsse insbesondere in der fernen Zukunft zu. Aussagen zu größeren Ereignissen sind aufgrund der großen Bandbreite der Ergebnisse jedoch mit erheblichen Unsicherheiten behaftet. Die Niedrigwasserverhältnisse zeigten eine Abnahme der Abflüsse, speziell im Sommer, sowie eine Zunahme der Dauer undnder Volumendefizite bei Trockenperioden. Hierbei erschien die Variabilität und Ausprägung der Trockenheit in kleineren Einzugsgebieten etwas größer. Die Nutzung dieser Erkenntnisse stellt die fachliche Praxis vor die Herausforderung, die Ergebnisse zu interpretieren und zu kommunizieren. Unsicherheiten in den Modellketten müssen berücksichtigt und, wenn möglich, quantifiziert werden. Die abgeleiteten hydrologischen Konsequenzen des Klimawandels können z.B. Anwendung finden in der gesetzlich geforderten Berücksichtigung der Auswirkungen des Klimawandels auf die Risikogebiete entsprechend der Hochwasserrisikomanagement-Richtlinie (2007/60/EG). Dieser Beitrag gibt einen Überblick über wasserwirtschaftlich relevante Auswertungen von Klimamodelldaten auf unterschiedlichen räumlichen Skalen und zeigt anhand ausgewählter Beispiele auf, wie primär im wissenschaftlichen Kontext erhobene Ergebnisse effektiv für praxisrelevante Fragestellungen genutzt werden können

BPIFB1 is a lung-specific autoantigen associated with interstitial lung disease.

Interstitial lung disease (ILD) is a complex and heterogeneous disorder that is often associated with autoimmune syndromes. Despite the connection between ILD and autoimmunity, it remains unclear whether ILD can develop from an autoimmune response that specifically targets the lung parenchyma. We examined a severe form of autoimmune disease, autoimmune polyglandular syndrome type 1 (APS1), and established a strong link between an autoimmune response to the lung-specific protein BPIFB1 (bactericidal/permeability-increasing fold-containing B1) and clinical ILD. Screening of a large cohort of APS1 patients revealed autoantibodies to BPIFB1 in 9.6% of APS1 subjects overall and in 100% of APS1 subjects with ILD. Further investigation of ILD outside the APS1 disorder revealed BPIFB1 autoantibodies present in 14.6% of patients with connective tissue disease-associated ILD and in 12.0% of patients with idiopathic ILD. The animal model for APS1, Aire⁻/⁻ mice, harbors autoantibodies to a similar lung antigen (BPIFB9); these autoantibodies are a marker for ILD. We found that a defect in thymic tolerance was responsible for the production of BPIFB9 autoantibodies and the development of ILD. We also found that immunoreactivity targeting BPIFB1 independent of a defect in Aire also led to ILD, consistent with our discovery of BPIFB1 autoantibodies in non-APS1 patients. Overall, our results demonstrate that autoimmunity targeting the lung-specific antigen BPIFB1 may contribute to the pathogenesis of ILD in patients with APS1 and in subsets of patients with non-APS1 ILD, demonstrating the role of lung-specific autoimmunity in the genesis of ILD

Injectable gellan gum-based nanoparticles-loaded system for the local delivery of vancomycin in osteomyelitis treatment

Infection spreading in the skeletal system leading to osteomyelitis can be prevented by the prolonged administration of antibiotics in high doses. However systemic antibiotherapy, besides its inconvenience and often low efficacy, provokes numerous side effects. Thus, we formulated a new injectable nanoparticle-loaded system for the local delivery of vancomycin (Vanc) applied in a minimally-invasive way. Vanc was encapsulated in poly(Llactide- co-glycolide) nanoparticles (NPs) by double-emulsification. The size (258 ± 11 nm), polydispersity index (0.240 ± 0.003) and surface potential (-25.9 ± 0.2 mV) of NPs were determined by dynamic light scattering and capillary electrophoresis measurements. They have a spherical morphology and a smooth topography as observed using atomic force microscopy. Vanc loading and encapsulation efficiencies were 8.8 ± 0.1 and 55.2 ± 0.5 %, respectively, based on fluorescence spectroscopy assays. In order to ensure injectability, NPs were suspended in gellan gum and cross-linked with $Ca^{2+}$; also a portion of dissolved antibiotic was added to the system. The resulting system was found to be injectable (extrusion force 11.3 ± 1.1 N), reassembled its structure after breaking as shown by rheology tests and ensured required burst release followed by sustained Vanc delivery. The system was cytocompatible with osteoblast-like MG-63 cells (no significant impact on cells’ viability was detected). Growth of Staphylococcus spp. reference strains and also those isolated from osteomyelitic joints was inhibited in contact with the injectable system. As a result we obtained a biocompatible system displaying ease of application (low extrusion force), self-healing ability after disruption, adjustable drug release and antimicrobial properties