Hyperthermic superparamagnetic nanoparticles modulate adipocyte metabolism

Adipocytes are the principal cellular component in adipose tissue and their excessive hyperplasia or hypertrophy is actively involved in regulating physiologic and pathologic processes such as inflammation, cardiovascular disease, obesity and tumour. The main depot of energy in adipocytes is represented by lipid droplets, intracellular organelles that play fundamental roles in regulation of metabolic processes. An accumulation of such droplets could be a potential biomarker of disease caused by metabolic dysregulation. Recent studies have demonstrated that heat shock is associated with alteration in energy metabolism: the aim of this study is to modulate the energy metabolism of the adipocytes via controlled administration of thermal energy to reduce the number of lipid droplets. We have investigated the effect of controlled heating of adipocytes using an alternating magnetic field (AMF) on samples loaded with superparamagnetic nanoparticles (MNP) as heating agent

Both Monoclonal and Polyclonal Immunoglobulin Contingents Mediate Complement Activation in Monoclonal Gammopathy Associated-C3 Glomerulopathy

C3 glomerulopathy (C3G) results from acquired or genetic abnormalities in the complement alternative pathway (AP). C3G with monoclonal immunoglobulin (MIg-C3G) was recently included in the spectrum of “monoclonal gammopathy of renal significance.” However, mechanisms of complement dysregulation in MIg-C3G are not described and the pathogenic effect of the monoclonal immunoglobulin is not understood. The purpose of this study was to investigate the mechanisms of complement dysregulation in a cohort of 41 patients with MIg-C3G. Low C3 level and elevated sC5b-9, both biomarkers of C3 and C5 convertase activation, were present in 44 and 78% of patients, respectively. Rare pathogenic variants were identified in 2/28 (7%) tested patients suggesting that the disease is acquired in a large majority of patients. Anti-complement auto-antibodies were found in 20/41 (49%) patients, including anti-FH (17%), anti-CR1 (27%), anti-FI (5%) auto-antibodies, and C3 Nephritic Factor (7%) and were polyclonal in 77% of patients. Using cofactor assay, the regulation of the AP was altered in presence of purified IgG from 3/9 and 4/7 patients with anti-FH or anti-CR1 antibodies respectively. By using fluid and solid phase AP activation, we showed that total purified IgG of 22/34 (65%) MIg-C3G patients were able to enhance C3 convertase activity. In five documented cases, we showed that the C3 convertase enhancement was mostly due to the monoclonal immunoglobulin, thus paving the way for a new mechanism of complement dysregulation in C3G. All together the results highlight the contribution of both polyclonal and monoclonal Ig in MIg-C3G. They provide direct insights to treatment approaches and opened up a potential way to a personalized therapeutic strategy based on chemotherapy adapted to the B cell clone or immunosuppressive therapy

C4 nephritic factor in patients with immune-complex-mediated membranoproliferative glomerulonephritis and C3-glomerulopathy

L

Caractérisation des anomalies héréditaires et acquises au cours du syndrome hémolytique et urémique atypique et de la glomérulopathie à dépôts de C3

Résumé confidentielConfidential abstrac

Long-term study on symptomless human metapneumovirus infection in hematopoietic stem cell transplant recipients

From October 2004 through October 2006 a study was performed to evaluate the prevalence of human Metapneumovirus (hMPV) infection in adult hematopoietic stem cell transplant (HSCT) recipients. Sequential nasopharyngeal aspirates (NPA) were collected independently from respiratory symptoms and evaluated for hMPV-RNA by polymerase chain reaction (PCR) and sequence analysis. Results indicate epidemiological and molecular differences between the 2004-2005 and 2005-2006 periods and that hMPV seems not to symptomatically affect HSCT patients or cause late respiratory sequelae. In addition, data collected suggest a hospital origin of hMPV infection in most HSCT patients during the 2004-2005 period

Innovative approach to safely induce controlled lipolysis by superparamagnetic iron oxide nanoparticles-mediated hyperthermic treatment

During last years, evidence has been provided on the involvement of overweight and obesity in the pathogenesis and aggravation of several life-threatening diseases. Here, we demonstrate that, under appropriate administration conditions, polyhedral iron oxide nanoparticles are efficiently and safely taken up by 3T3 cell line-derived adipocytes (3T3 adipocytes) in vitro. Since these nanoparticles proved to effectively produce heat when subjected to alternating magnetic field, 3T3 adipocytes were submitted to superparamagnetic iron oxide nanoparticles-mediated hyperthermia treatment (SMHT), with the aim of modulating their lipid content. Notably, the treatment resulted in a significant delipidation persisting for at least 24h, and in the absence of cell death, damage or dedifferentiation. Interestingly, transcript expression of adipose triglyceride lipase (ATGL), a key gene involved in canonical lipolysis, was not modulated upon SMHT, suggesting the involvement of a novel/alternative mechanism in the effective lipolysis observed. By applying the same experimental conditions successfully used for 3T3 adipocytes, SMHT was able to induce delipidation also in primary cultures of human adipose-derived adult stem cells. The success of this pioneering approach in vitro opens promising perspectives for the application of SMHT in vivo as an innovative safe and physiologically mild strategy against obesity, potentially useful in association with balanced diet and healthy lifestyle

Anti-Factor B and Anti-C3b Autoantibodies in C3 Glomerulopathy and Ig-Associated Membranoproliferative GN

International audienceIn C3 glomerulopathy (C3G), the alternative pathway of complement is frequently overactivated by autoantibodies that stabilize the C3 convertase C3bBb. Anti-C3b and anti-factor B (anti-FB) IgG have been reported in three patients with C3G. We screened a cohort of 141 patients with C3G and Ig-associated membranoproliferative GN (Ig-MPGN) for anti-FB and anti-C3b autoantibodies using ELISA. We identified seven patients with anti-FB IgG, three patients with anti-C3b IgG, and five patients with anti-FB and anti-C3b IgG. Of these 15 patients, ten were diagnosed with Ig-MPGN. Among those patients with available data, 92% had a nephrotic syndrome, 64% had AKI, and 67% had a documented infection. Patients negative for anti-C3b and anti-FB IgG had much lower rates of infection (17 [25%] patients with C3G and one [10%] patient with Ig-MPGN). After 48 months, four of 15 (26%) positive patients had developed ESRD or died. All 15 patients had high plasma Bb levels, six (40%) patients had low levels of C3, and nine (60%) patients had high levels of soluble C5b9. In vitro, IgG purified from patients with anti-FB Abs selectively enhanced C3 convertase activity; IgG from patients with anti-C3b/anti-FB Abs enhanced C3 and C5 cleavage. IgG from patients with anti-C3b Abs stabilized C3bBb and perturbed C3b binding to complement receptor 1 but did not perturb binding to factor H. In conclusion, the prevalence of anti-C3b/anti-FB Abs and alternative pathway activation is similar in Ig-MPGN and C3G, suggesting similar pathogenic mechanisms. Identification of the underlying defect in Ig-MPGN could lead to improved treatment

Both Monoclonal and Polyclonal Immunoglobulin Contingents Mediate Complement Activation in Monoclonal Gammopathy Associated-C3 Glomerulopathy

International audienceC3 glomerulopathy (C3G) results from acquired or genetic abnormalities in the complement alternative pathway (AP). C3G with monoclonal immunoglobulin (MIg-C3G) was recently included in the spectrum of "monoclonal gammopathy of renal significance." However, mechanisms of complement dysregulation in MIg-C3G are not described and the pathogenic effect of the monoclonal immunoglobulin is not understood. The purpose of this study was to investigate the mechanisms of complement dysregulation in a cohort of 41 patients with MIg-C3G. Low C3 level and elevated sC5b-9, both biomarkers of C3 and C5 convertase activation, were present in 44 and 78% of patients, respectively. Rare pathogenic variants were identified in 2/28 (7%) tested patients suggesting that the disease is acquired in a large majority of patients. Anti-complement auto-antibodies were found in 20/41 (49%) patients, including anti-FH (17%), anti-CR1 (27%), anti-FI (5%) auto-antibodies, and C3 Nephritic Factor (7%) and were polyclonal in 77% of patients. Using cofactor assay, the regulation of the AP was altered in presence of purified IgG from 3/9 and 4/7 patients with anti-FH or anti-CR1 antibodies respectively. By using fluid and solid phase AP activation, we showed that total purified IgG of 22/34 (65%) MIg-C3G patients were able to enhance C3 convertase activity. In five documented cases, we showed that the C3 convertase enhancement was mostly due to the monoclonal immunoglobulin, thus paving the way for a new mechanism of Chauvet et al. C3 Glomerulopathy and Monoclonal Gammopathy complement dysregulation in C3G. All together the results highlight the contribution of both polyclonal and monoclonal Ig in MIg-C3G. They provide direct insights to treatment approaches and opened up a potential way to a personalized therapeutic strategy based on chemotherapy adapted to the B cell clone or immunosuppressive therapy

Politiche professionali: studio qualitativo sulle percezioni e le opinioni dei professionisti infermieri/ostetriche e degli studenti della Laurea magistrale in Scienze infermieristiche e ostetriche.

Introduzione. La politica, ovvero la scienza e l'arte di amministrare la cosa pubblica, è un ambito di grande importanza e occuparsi di politica professionale significa dedicarsi al bene della professione. Le politiche professionali sono parte integrante del prendersi cura e la famiglia professionale ha bisogno di punti chiari di riferimento: formazione, tutela, promozione, rappresentanza istituzionale.Obiettivo. Esplorare percezioni, idealití , immaginario condiviso e desideri circa le politiche professionali di infermieri/ostetriche e studenti della laurea magistrale per riuscire ad avere una rappresentazione della realtí  e avviare una riflessione critica sul tema. Metodo. È stato effettuato uno studio qualitativo su un campione propositivo di 22 professionisti infermieri/ostetriche quali testimoni qualificati della situazione nazionale. I dati sono stati raccolti attraverso un questionario costruito ad hoc.Risultati. Dall'analisi delle risposte sono emersi 10 temi principali, tra i quali spiccano: per la formazione l'importanza delle nuove conoscenze ma anche la scarsa differenziazione dei ruoli; per l'ambito lavorativo l'assenza di meritocrazia e di nuove opportunití ; per la ricerca il divario tra teoria e pratica. In sintesi, i risultati evidenziano come la partecipazione ai processi di formazione delle politiche sia saltuaria e di poca intensití  e come pochi infermieri/ostetriche siano coinvolti attivamente per la promozione e sviluppo di progetti nel settore delle politiche per i sistemi sanitari e per la salute.Conclusioni. L'indagine rileva che vi è una coscienza forte delle problematicití  esistenti, ma questa coscienza non sembra relazionarsi adeguatamente ai contesti lavorativi, istituzionali e culturali. Di conseguenza non si verifica quella necessaria crescita delle politiche professionali, la sola capace di generare percorsi politici atti a risolvere le questioni di fondo. Parole chiave: politica sanitaria, partecipazione politica, infermieri/ostetriche, leadership politica.Professional policies: a qualitative study of perceptions and opinions of professionals nurses/midwives and students attending the Master of Science in NursingABSTRACTIntroduction. Politics, the science and the art of administering public affairs, is a very important field. Dealing with professional policy means to dedicate ourselves to the good of the profession. Professional policies are an integral part of taking care; the professional family needs clear reference points: training, tutoring, promotion and institutional representation.Aim. Exploring perceptions, ideals, shared imagination and desires about the professional policies of nurses/midwives and of master's students in order to be able to have a representation of the reality and to start a critical reflection on the subject. Method. A qualitative study was conducted on a proactive sample of 22 nurses / midwives as qualified witnesses of the national situation. The data was collected through a questionnaire built ad hoc.Results.  From the analysis of the answers given to the questionnaire, we identified 10 main themes. In the training sector two of the themes that were selected are the importance of the new knowledges and inadequate differentiation of the positions; Regarding the working sector two of the themes that came out are the lack of meritocracy and of new opportunities; meanwhile, in the research field one of the main theme identified is the gap between the theory and the practice.Conclusions.  The present study finds out that participation in policy-making processes is occasional and of little intensity: just few nurses/midwives are actively involved in the promotion and development of projects in the health sector and of healthcare policies. Keywords: health policy, political participation, nurses/midwiferies, political leadership