Un modello di filtrazione glomerulare selettivo per le varianti di albumina umana

L’albumina (HSA) è la proteina più abbondante nel plasma umano, in esso svolge una serie di funzioni tra cui il mantenimento della pressione oncotica del plasma, la regolazione del tono vascolare attraverso il trasporto e il rilascio di NO, il trasporto di metalli pesanti e di ioni e la difesa contro i radicali liberi dell’ossigeno. Queste funzioni, anche se non sono tutte quelle svolte dall’albumina, sono consentite dalla plasticità di questa proteina che può realizzare una serie di microtransizioni cambiando la pKs dei gruppi ionizzabili in relazione al pH o al ligando con cui interagisce. Lo scopo principale di questa tesi è di mettere in luce che, seguendo le modificazioni dell’albumina, alcune alterazioni della funzione filtrante del glomerulo possono essere causate da una eterogenea popolazione di pori glomerulari. Questi possono avere sia dimensioni sia struttura elettrochimica diverse, dal momento che nel corso delle glomerulopatie vengono perse quantità variabili di cariche negative affacciate dalla parte luminale dei pori, dove vengono filtrate normalmente le proteine. La seconda variabile può essere dovuta alle molecole da filtrare le quali subiscono modificazioni di struttura e quindi di carica; anche in questo caso si ha una alterazione della filtrazione glomerulare. In questa tesi sono studiate alcune forme di albumina variante. Sia studi indiretti sia un’unica ipotesi, evidenziano come le varianti di albumina vengono escluse dalla filtrazione e permangono nel siero, dove subiscono anche proteolisi specifiche: anche i peptidi prodotti dalla proteolisi non vengono filtrati dal glomerulo, oppure vengono completamente riassorbiti a livello tubulare. Ne consegue che la proteina modificata elettrostaticamente determina una alterazione della filtrazione glomerulare, a parità di grandezza omogenea dei pori glomerulari. E’ stato analizzato un modello matematico sulla specificità della filtrazione da parte della barriera glomerulare e studi sia antecedenti al modello sia successivi ad esso ne confermano la validità. In alcuni casi è stata dimostrata la validità per il modello a pori omogenei senza varianti nelle proteine, in altri casi quello ad isoporo non è stato ritenuto valido ed è stato così affrontato il sistema di filtrazione secondo un modello eteroporoso, con le conseguenti verifiche e dimostrazioni della sua efficacia

D'histoires oubliées et langues perdues. Le lexique comme outil de recherche dans l'histoire de l'alchimie et de la chimie

In an academic environment devoted to a progressive anglicisation of the scientific debate, how can we achieve exhaustive results – within historicophilosophical analysis – having to deal with sources written in a multiplicity of languages, including the specific vocabularies of obsolete or extinct epistemological systems? The present paper questions the possibility of creating specific lexicons, both period- and author-oriented, as dedicated research tools for historians of science

Il pianoforte di Einstein

Se gli oggetti potessero parlare potrebbero raccontare molte storie delle persone a cui sono appartenuti, ma anche dei tempi che hanno attraversato. Questo libro racconta l’inedita storia del pianoforte regalato da Einstein alla sorella Maja nel 1931, poi passato nelle mani del pittore Hans Joachim Staude e ora conservato all’Osservatorio Astrofisico di Arcetri. Attraverso fonti e immagini, viene così ricostruito il legame di Einstein con l’Italia, e soprattutto con Firenze, tra scienza, arte e cultura, all’epoca dell’avvento del fascismo, della questione ebraica, delle leggi razziali e della guerra fino all’emigrazione negli Stati Uniti. Una vicenda costellata di avvenimenti a volte meravigliosi, a volte tragici, mai banali. Un’avventura vissuta a fianco delle vite di molte donne e uomini che hanno dovuto confrontarsi con sfide quotidiane ed epocali, accompagnate da un filo conduttore, la musica, che ha legato in maniera indissolubile le loro esistenze

HIV-2 infection in a migrant from Gambia: the history of the disease combined with phylogenetic analysis revealed the real source of infection

Human immunodeficiency virus type 2 (HIV-2) infection prevalence is increasing in some European countries. The increasing migratory flow from countries where HIV-2 is endemic has facilitated the spread of the virus into Europe and other regions. We describe a case of HIV-2 infection in a migrant individual in the Asylum Seeker Centre (ASC) in Italy. The patient's virus was sequenced, and found to be a typical HIV-2 genotype A virus. Bayesian evolutionary analysis revealed that the HIV-2 sequence from migrant dated back to 1986 in a subcluster including sequences from Guinea Bissau. This was coherent with the migrant history who lived in Guinea Bissau from his birth until 1998 when he was 13 years old. Monitoring for HIV-2 infection in migrants from western Africa is necessary using adequate molecular tools to improve the diagnosis and understand the real origin of infection

Dynamic changes of mmp-9 plasma levels correlate with jvc reactivation and immune activation in natalizumab-treated multiple sclerosis patients

The aim of the study was to investigate the changes of matrix metalloproteinase (MMP)-2 and MMP-9 plasma levels during natalizumab treatment and their correlation with JC virus (JCV) reactivation and T-lymphocyte phenotypic modifications in peripheral blood samples from 34 relapsing-remitting multiple sclerosis (RRMS) patients. MMP-9 levels were assessed by zymography in plasma samples. JCV-DNA was detected through quantitative real time PCR in plasma samples. T-lymphocyte phenotype was assessed with flow cytometry. MMP-9 plasma levels resulted increased from 12 to 24 natalizumab infusions. Stratifying plasma samples according to JCV-DNA detection, MMP-9 plasma levels were significantly increased in JCV-DNA positive than JCV-DNA negative samples. MMP-9 plasma levels resulted positively correlated with JCV viral load. CD4 immune senescence, CD8 immune activation and CD8 effector percentages were positively correlated to MMP-9 plasma levels, whereas a negative correlation between CD8 naïve percentages and MMP-9 plasma levels was found. Our data indicate an increase of MMP-9 plasma levels between 12 and 24 natalizumab infusions and a correlation with JCV-DNA detection in plasma, T-lymphocyte immune activation and senescence. These findings could contribute to understand PML pathogenesis under natalizumab treatment, suggesting a potential role of MMP-9 as a predictive marker of PML in RRMS patients

Broadband stimulated Raman scattering with Fourier-transform detection

We propose a new approach to broadband Stimulated Raman Scattering (SRS) spectroscopy and microscopy based on time-domain Fourier transform (FT) detection of the stimulated Raman gain (SRG) spectrum. We generate two phase-locked replicas of the Stokes pulse after the sample using a passive birefringent interferometer and measure by the FT technique both the Stokes and the SRG spectra. Our approach blends the very high sensitivity of single-channel lock-in balanced detection with the spectral coverage and resolution afforded by FT spectroscopy. We demonstrate our method by measuring the SRG spectra of different compounds and performing broadband SRS imaging on inorganic blends

Reactivation of hepatitis B virus with immune-escape mutations after ocrelizumab treatment for multiple sclerosis

Ocrelizumab is an anti-CD20 monoclonal antibody for the treatment of multiple sclerosis (MS) that is closely related to rituximab. We describe a case of hepatitis B virus (HBV) reactivation in an MS patient with resolved HBV infection receiving ocrelizumab. HBV reactivation was monitored with HBV-DNA and HBV surface antigen periodic assessment. Anti-HBV treatment with entecavir was started after HBV-DNA detection. Ocrelizumab can reactivate viral replication in patients with resolved HBV infection. HBV reactivation monitoring seems an effective and safe option for the management of these patients. More studies are needed to assess the optimal management of HBV reactivation in MS patients on ocrelizumab treatment

Higher levels of osteoprotegerin and immune activation/immunosenescence markers are correlated with concomitant bone and endovascular damage in HIV-suppressed patients

HIV-infected patients appear to have a significantly greater risk of non-AIDS comorbidities such as osteoporosis and atherosclerosis. Subjects with osteoporosis are at a higher risk of developing cardiovascular disease than those with normal bone mass, therefore a possible relation between these two conditions can be hypothesized. In the setting of HIV infection, several factors might contribute to bone disease and endothelial dysfunction. The aim of our study was to evaluate the relationship between bone and cardiovascular disease and to investigate the role of traditional factors, T-cell phenotype and osteoprotegerin in HIV positive subjects on effective antiretroviral therapy. We included 94 HIV positive subjects on antiretroviral therapy with virological suppression and 41 healthy subjects matched for age and gender as a control group. Carotid-Intima Media Thickness (c-IMT) and bone mineral density (BMD) were performed by ultrasound and DEXA, respectively. CD4+/CD8+ T-cell activation, senescence and osteoprotegerin plasma levels were measured by flow-cytometry and ELISA, respectively. Among HIV positive patients, 56.4% had osteopenia/osteoporosis and 45.7% had pathological c-IMT (>0.9mm). Subjects with pathological c-IMT and BMD exhibited higher CD4+ and CD8+ activated, CD8+ senescent and osteoprotegerin than subjects with normal c-IMT and BMD. HIV positive subjects with osteopenia/osteoporosis had higher c-IMT than subjects with normal BMD, and linear regression analysis showed a negative correlation between BMD and c-IMT. Several factors are implicated in the pathogenesis of non-AIDS comorbidities in HIV positive patients. Osteoprotegerin together with inflammation and immunosenescence in HIV positive patients could affect bone and vascular system and could be considered as a possible common link between these two diseases

JC virus-DNA detection is associated with CD8 fffector accumulation in peripheral blood of patients with multiple sclerosis under natalizumab treatment, independently from JC virus serostatus

Although natalizumab (anti-α4 integrin) represents an effective therapy for relapsing remitting multiple sclerosis (RRMS), it is associated with an increased risk of developing progressive multifocal leukoencephalopathy (PML), caused by the polyomavirus JC (JCV). The aim of this study was to explore natalizumab-induced phenotypic changes in peripheral blood T-lymphocytes and their relationship with JCV reactivation. Forty-four patients affected by RRMS were enrolled. Blood and urine samples were classified according to natalizumab infusion number: 0 (N0), 1-12 (N12), 13-24 (N24), 25-36 (N36), and over 36 (N > 36) infusions. JCV-DNA was detected in plasma and urine. T-lymphocyte phenotype was evaluated with flow cytometry. JCV serostatus was assessed. Ten healthy donors (HD), whose ages and sexes matched with the RRMS patients of the N0 group, were enrolled. CD8 effector (CD8 E) percentages were increased in natalizumab treated patients with detectable JCV-DNA in plasma or urine compared to JCV-DNA negative patients (JCV-) (p < 0.01 and p < 0.001, resp.). Patients with CD8 E percentages above 10.4% tended to show detectable JCV-DNA in plasma and/or urine (ROC curve p = 0.001). The CD8 E was increased when JCV-DNA was detectable in plasma or urine, independently from JCV serology, for N12 and N24 groups (p < 0.01). As long as PML can affect RRMS patients under natalizumab treatment with a negative JCV serology, the assessment of CD8 E could help in the evaluation of JCV reactivation