Small bowel pseudomelanosis and oral iron therapy

Small bowel pseudomelanosis is a rarely reported clinical entity characterized by brown pigmentation of small bowel mucosa. The authors describe two cases, both with iron deficiency anemia, one of an 81-year-old female patient submitted for capsule endoscopy that revealed a brown pigmentation of all small bowel mucosa and another of an 81-year-old male whose retrograde double-balloon enteroscopy revealed a diffuse brown pattern of small bowel mucosa. Ileal biopsies confirmed intense iron deposition in the macrophages of the lamina propria. Both patients were on oral iron therapy and the second one had a previous double-balloon enteroscopy, 2 years earlier, which revealed only ileal angiodysplasias. These two cases demonstrate the importance of two new endoscopic methods for diagnosis of small bowel pseudomelanosis, the rarity of such an entity and its close relation with oral iron therapy.

La gestione del portafoglio brevettuale del Dipartimento Energia e Trasporti

Prima della presente riforma del CNR, esisteva all’interno dell’Ente un Ufficio Brevetti, che supportava i propri ricercatori, a livello nazionale, nelle fasi di primo deposito, estensione all’estero, nella stipula di contratti di cessione e di licenza. Dal momento in cui è entrato in vigore il decreto di riordino dell’Ente (D.L. 4 giugno 2003, n. 127) e si sono creati e avviati gli 11 Dipartimenti, l’ufficio brevetti è stato soppresso e il portafoglio brevettuale è stato affidato ai Dipartimenti, ognuno con la propria macro area di competenza.

Protective effect of simvastatin in the cyclophosphamide-induced hemohrragic cystitis in rats

Cyclophosphamide (CYP) is an antineoplastic agent used for the treatment of many neoplastic and inflammatory diseases. Hemorrhagic cystitis is a frequent side effect of CYP. Several studies show that simvastatin has important pleiotropic (anti-inflammatory and immunomodulatory) effects. The purpose of the study was to investigate the effect of simvastatin on bladder, ureter and kidney injury caused by CYP. Methods: Adult male Wistar rats were randomly divided into three groups. The CYP/SIM group received simvastatin microemulsion by gavage during 7 days (10 mg/kg body wt) before the administration of CYP and the CYP/SAL group rats received saline 0.9%. The control rats were not treated. After that, all rats were treated with a single dose of CYP 200 mg/kg body wt intraperitoneally. The rats were killed 24 h after CYP administration. Plasma cytokines (TNF-a, IL-1b, IL-6) were measured by ELISA. Macro and light microscopic study was performed in the bladder, kidney and ureter. Results: In the bladders of CYP/SIMV treated rats edema of lamina propria with epithelial and sub-epithelial hemorrhage were lower than in CYP/SAL treated rats. The scores for macroscopic and microscopic evaluation of bladder and ureter were significantly lower in CYP/SIMV rats than in CYP/SAL rats. The kidney was not affected. The expression of TNF-a, IL-1b and IL-6 was significatly lower in CF/SINV rats (164.8±22, 44.8±8 and 52.4±13) than in CF/SAL rats (378.5±66, 122.9±26 e 123.6±18), respectively. Conclusion: The results of the current study suggest that simvastatin pretreatment attenuated CYP-induced urotelium inflammation and decreased the activities of cytokines

Comparison of prophylactic and therapeutic use of short-chain fatty acid enemas in diversion colitis: a study in Wistar rats

OBJECTIVES: To study the effect of short-chain fatty-acids on atrophy and inflammation of excluded colonic segments before and after the development of diversion colitis. INTRODUCTION: Diversion colitis is a chronic inflammatory process affecting the dysfunctional colon, possibly evolving with mucous and blood discharge. The most favored hypotheses to explain its development is short-chain fatty-acid deficiency in the colon lumen. METHODS: Wistar rats were submitted to colostomy with distal colon exclusion. Two control groups (A1 and B1) received rectally administered physiological saline, whereas two experimental groups (A2 and B2) received rectally administered short-chain fatty-acids. The A groups were prophylactically treated (5th to 40th days postoperatively), whereas the B groups were therapeutically treated (after post-operative day 40). The mucosal thickness of the excluded colon was measured histologically. The inflammatory reaction of the mucosal lamina propria and the lymphoid tissue response were quantified through established scores. RESULTS: There was a significant thickness recovery of the colonic mucosa in group B2 animals (p = 0.0001), which also exhibited a significant reduction in the number of eosinophilic polymorphonuclear cells in the lamina propria (p = 0.0126) and in the intestinal lumen (p = 0.0256). Group A2 showed no mucosal thickness recovery and significant increases in the numbers of lymphocytes (p = 0.0006) and eosinophilic polymorphonuclear cells in the lamina propria of the mucosa (p = 0.0022). CONCLUSION: Therapeutic use of short-chain fatty-acids significantly reduced eosinophilic polymorphonuclear cell numbers in the intestinal wall and in the colonic lumen; it also reversed the atrophy of the colonic mucosa. Prophylactic use did not impede the development of mucosal atrophy

Evaluation of alpha-synuclein immunohistochemical methods for the detection of Lewy-type synucleinopathy in gastrointestinal biopsies

International audience

Development of dendritic cells in the intestine

The intestinal tract is exposed to a large variety of antigens such as food proteins, commensal bacteria and pathogens and contains one of the largest arms of the immune system. The intestinal immune system has to discriminate between harmless and harmful antigens, inducing tolerance to harmless antigens and active immunity towards pathogens and other harmful materials. Dendritic cells (DC) in the mucosal lamina propria (LP) are central to this process, as they sample bacteria from the local environment and constitutively migrate to the draining mesenteric lymph nodes (MLN), where they present antigen to naïve T cells in order to direct an appropriate immune response. Despite their crucial role, understanding the function and phenotype of LP DC has been hampered by the fact that they share phenotypic markers with macrophages (mφ), which are the dominant population of mononuclear phagocyte (MP) in the LP. Recent work in our own and other laboratories has established gating strategies and phenotyping panels that allow precise discrimination between intestinal DC and mφ using the mφ specific markers CD64 and F4/80. In this way four bona fide DC subsets with distinct functions have been identified in adult LP based on their expression of CD11b and CD103 and a major aim of my project was to understand how these subsets might develop in the neonatal intestine. At the beginning of my PhD, the laboratory had used these new methods to show that signal regulatory protein α (SIRPα), an inhibitory receptor expressed by myeloid cells, was expressed by mφ and most DC in the intestine, except for those expressing CD103 alone. In addition, mice carrying a non-signalling mutation in SIRPα (SIRPα mt) had a selective reduction in CD103+CD11b+ DC, a subset which is unique to the intestinal LP. This was the basis for the initial experiments of my project, described in Chapter 3, where I investigated if the phenotype in SIRPα mt mice was intrinsic to haematopoietic cells or not. To explore this, I generated bone marrow (BM) chimeric mice by reconstituting irradiated WT mice with SIRPα mt BM, or SIRPα mt animals with WT BM. These experiments suggested that the defect in CD103+CD11b+ DC was not replicated in DC derived from BM of SIRPα origin. However as this seemed inconsistent with other data, I considered the possibility that 18 the phenotype may have been lost with age, as the BM chimeric mice were considerably older than those used in the original studies of SIRPα function. However a comparison of DC subsets in the intestine of WT and SIRPα mt mice as they aged provided no conclusive evidence to support this idea. As these experiments did show age-dependent effects on DC subsets, in Chapter 4, I went on to investigate how the DC populations appeared in the intestine and other tissues in the neonatal period. These experiments showed there were few CD103+CD11b+ DC present in the LP and migratory DC compartment of the MLN in the neonate and that as this population gradually increased in proportion with age, there was a reciprocal decrease in the relative proportion of CD103-CD11b+ DC. Interestingly, most of the changes in DC numbers in the intestine were found during the second or third week of life when the weaning process began. To validate my findings that there were few CD103+CD11b+ DC in the neonate and that this was not merely an absence of CD103 upregulation, I examined the expression of CD101 and Trem-1, markers that other work in the laboratory had suggested were specific to the CD103+CD11b+ DC lineage. My work showed that CD101 and Trem-1 were co- expressed by most CD103+CD11b+ DC in small intestine (SI) LP, as well as a small subset of CD103-CD11b+ DC in this tissue. Interestingly, Trem-1 was highly specific to the SI LP and migratory DC in the MLN, but absent from the colon and other tissues. CD101 expression was also only found on CD11b+ DC, but showed a less restricted pattern of distribution, being found in several tissues as well as the SI LP. The relative timing of their development suggested there might be a relationship between CD103+CD11b+ and CD103-CD11b+ DC and this was supported by microarray analysis. I hypothesised that the CD103-CD11b+ DC that co-expressed CD101 and Trem-1 may be the cells that developed into CD103+CD11b+ DC. To investigate this I analysed how CD101 and Trem-1 expression changed with age amongst the DC subsets in SI LP, colonic LP (CLP) and MLN. The proportion of CD101+Trem-1+ cells increased amongst CD103+CD11b+ DC in the SI LP and MLN with age, while amongst CD103+CD11b+ DC in the CLP this decreased. This was not the same in CD103-CD11b+ DC, where CD101 and Trem-1 expression was more varied with age in all tissues. CD101 and Trem-1 were not expressed to any great extent on CD103+CD11b- or CD103-CD11b- DC. The phenotypic development of the 19 intestinal DC subsets was paralleled by the gradual upregulation of CD103 expression, while the production of retinoic acid (RA), as assessed by the AldefluorTM assay, was low early in life and did not attain adult levels until after weaning. Thus DC in the neonatal intestine take some time to acquire the adult pattern of phenotypic subsets and are functionally immature compared with their adult counterparts. In Chapter 5, I used CD101 and Trem-1 to explore the ontogeny of intestinal DC subsets in CCR2-/- and SIRPα mt mice, both of which have selective defects in one particular group of DC. The selective defect seen amongst CD103+CD11b+ DC in adult SIRPα mt mice was more profound in mice at D7 and D14 of age, indicating that it may be intrinsic to this population and not highly dependent on environmental factors that change after birth. The expression of CD101 and Trem-1 by both CD103+CD11b+ and CD103-CD11b+ DC was reduced in SIRPα mt mice, again indicating that this entire lineage was affected by the lack of SIRPα signalling. However there was also a generalised defect in the numbers of all DC subsets in many tissues from early in life, suggesting there was compromised development, recruitment or survival of DC in the absence of SIRPα signalling. In contrast to the findings in SIRPα mt mice, more CD103+CD11b+ DC co-expressed CD101 and Trem-1 in CCR2-/- mice, while there were no differences in the expression of these molecules amongst CD103-CD11b+ DC. This may suggest that CCR2+ CD103-CD11b+ DC are not the cells that express CD101 and Trem-1 that are predicted to be the direct precursors of CD103+CD11b+ DC. I also examined the expression of DC growth factor receptors on DC subsets from mice of different ages, but no clear age or subset- related patterns of the expression of mRNA for Csf2ra, Irf4, Tgfbr1 and Rara could be observed. Next, I investigated whether Trem-1 played any role in DC development. Preliminary experiments in Trem-1-/- mice show no differences between any of the DC subsets, nor were there any selective effects on individual subsets when DC development from Trem-1-/- KO and WT BM was compared in competitive chimeras. However these experiments were difficult to interpret due to viability problems and because I found an unexpected defect in the ability of Trem-1-/- BM to generate all DC, irrespective of whether they expressed Trem-1 or not. 20 The final experiments I carried out were to examine the role of the microbiota in driving the differentiation of intestinal DC subsets, based on the hypothesis that this could be one of the environmental factors that might influence events in the developing intestine. To this end I performed experiments in both antibiotic treated and germ free adult mice, both of which showed no significant phenotypic differences amongst any of the DC subsets. However the study of germ free mice was compromised by recent contamination of the colony and may not be the conclusive answer. Together the data in this thesis have shown that the population of CD103+CD11b+ DC, which is unique to the intestine, is not present at birth. These cells gradually increase in frequency over time and as this occurs there is a reciprocal decrease in the frequency of CD103-CD11b+ DC. Along with other results, this leads to the idea that there may be a linear developmental pathway from CD103-CD11b+ DC to CD103+CD11b+ DC that is driven by non-microbial factors that are located preferentially in the small intestine. My project indicates that markers such as CD101 and Trem-1 may assist the dissection of this process and highlights the importance of the neonatal period for these events.

Lo sviluppo della radiofonia privata locale in Italia - un paragone alla situazione finlandese

Il monopolio statale si rompe in Italia già nel 1976 e le piccole antenne private sono nate come funghi. Talvolta gli studiosi hanno ipotizzato che questo settore radiofonico fiorisca e sia in continua crescita in Italia, comparato particolarmente alla situazione finlandese. Tra i radioascoltatori internazionali l'Italia è considerata il paradiso delle antenne locali per la gran quantità degli impianti radiofonici in ambito locale. Si ipotizza anche che la gran quantità delle stazioni di radio garantisca automaticamente l'obiettività dell'informazione, o almeno la polifonia della radio. Invece in Finlandia lo Stato ha limitato il diritto di impiantare una stazione radio e il numero delle stazioni in rete con una legge abbastanza rigida a livello europeo per controllare la privatizzazione del settore e la diffusione della nuova ideologia di radiofonia libera. Con la mia ricerca vorrei affermare la correttezza di tali ipotesi e, allo stesso tempo, verificare se l'Italia sia tuttora un paradiso di radiofonia locale. Uno degli scopi di questa ricerca è far capire che la formazione e la struttura del campo radiofonico dipende spesso della società intorno a sé. Dal momento che l'analisi si basa parzialmente sui metodi quantitativi, diamo un'occhiata ai numeri delle stazioni statali, reti nazionali e seminazionali e radio locali e provinciali nella provincia di Parma e in Finlandia Propria. Inoltre in questa tesi di laurea vorrei ricercare quali potrebbero essere i motivi storici, legislativi, culturali ed economici che hanno influito sul precoce sviluppo italiano nel campo della radiofonia locale. Per dare una più ampia visione della situazione italiana, ho fatto delle osservazioni sulla struttura del campo radiofonico in questi due paesi, sulle differenze essenziali tra Finlandia e Italia e sui motivi che influiscono nella nascita della radiofonia privata in ambito locale paragonando i fatti italiani con quelli finlandesi. Questa ricerca può dare un contributo importante agli appassionati del radioascolto ed essere utile come inizio di una più vasta valutazione di radiofonia locale per coloro che sono interessati ai mass media come mezzi di comunicazione, di potere e di democrazia. Contrariamente agli articoli anteriori e alle ricerche fatte, ormai la radiofonia provinciale non ha più molta importanza in Italia. Possiamo dire che non ci sia più un modello italiano da ammirare, perché le reti nazionali dominano le frequenze e raccolgono ormai un pubblico di dimensioni ragguardevoli e in continua crescita. Anche se il numero delle emittenti locali è diminuito notevolmente nella provincia di Parma, non possiamo concludere che la radiofonia locale in Italia sia morta basandosi su una sola ricerca che riguarda il cambiamento della struttura radiofonica in una località italiana.

Evaluation of Calretinin as a New Marker in the Diagnosis of Hirschsprung Disease

Background: Hirschsprung’s disease (HD) is a congenital intestinal motility disorder with absence of ganglion cells in the colonic wall. Diagnosis of the disease is mainly based on the identification of the lack of ganglion cells in the pathology sections of the colon which is very difficult and time consuming and also needs several serial cut sections. There are many proposed markers in this field in the literature but none of them has been satisfactory. Calretinin immunohistochemistry (IHC) has been introduced as a new diagnostic marker to overcome the problems in diagnosis of this disease about 5 years ago. However there are few studies regarding the benefits and pitfalls of this marker. Objectives: The aim of this study is to determine the diagnostic value of calretinin IHC in detecting aganglionosis (HD). Patients and Methods: 27 HD patients and 28 non-Hirschsprung’s disease (NHD) patients were collected in a prospective study and calretinin IHC was performed on 31 aganglionic and 51 normoganglionic full wall thickness sections of colectomies (some of the cases had more than 1 section). The IHC slides were evaluated by two pathologists and the diagnostic value was calculated in comparison with gold standard which is the presence or absence of ganglion cells in serial Hematoxylin and Eosin (HE) stained sections of the colectomies. Results: There was great concordance between the final diagnosis of both pathologists and gold standard (k > 0.9). Calretinin immunostaining showed 100% specificity and positive predictive value and more than 90% sensitivity and negative predictive value. High agreement was present between the two pathologists (k > 0.9). Conclusions: Calretinin IHC is a very convenient, useful and valuable method to demonstrate aganglionosis in HD patients. Loss of calretinin immunostaining in lamina propria and submucosa is characteristic of HD.

Effects of glyphosate-resistant crops on water quality.

2009

Sistemi di Mobile-Health per il monitoraggio e l'assistenza alla gravidanza

Con il termine "Mobile-Health" si intende l’uso di tecnologie mobili in ambito medico-sanitario. Questa tesi si propone di fornire un quadro generale di come i sistemi di Mobile-Health possano aiutare nell'assistenza e nel monitoraggio della gravidanza. Attraverso l'analisi delle ricerche effettuate in questo campo, e lo studio dei sistemi attualmente utilizzati in ambito ospedaliero, si cerca di valutare se effettivamente questo tipo di tecnologie può fornire un contributo significativo nell'assistere le donne incinte. Viene trattato il tema del Self-Management che riguarda appunto l'auto-gestione della propria condizione di salute attraverso l’uso di tecnologie mobili. Vengono introdotti problemi e complicazioni della gravidanza e i corrispettivi trattamenti. Si analizzano studi e ricerche che riguardano dispositivi e software per le donne incinte, compreso il tema delle “app mediche”. Infine, grazie al contributo delle dottoresse Iliana Colonna e Marina Carfagna (coordinatrici ostetriche negli ospedali di Rimini e Cesena), si presenta una panoramica sull’attuale uso di tecnologie nei reparti ospedalieri di ostetricia.

Il monolite di copertura del Mausoleo di Teodorico in Ravenna: commento alle ipotesi sulla sua messa in opera

Nella tesi si cerca di dare una nuova chiave di lettura del monumento unico nel suo genere, quanto noto Parliamo del Mausoleo di Teodorico che si erige nelle immediate vicinanze del centro di Ravenna.Il Mausoleo costruito nel v secolo, quando Ravenna è capitale dell’impero d’Occidente e vi si stabilisce Teodorico il Grande. La struttura è stata molto esaminata nel corso del tempo da molti studiosi ma non si ha notizia di una analisi d'insieme. Si è cercato quindi di mettere a fuoco uno degli aspetti più emblematici ed ancor ben lungi da scientifiche certezze: La sua copertura.Si tratta di un monolite con un peso stimato tra le 240 e le 270 Tonnellate proveniente dalle cave di Aurisina in Istria. Numerosi studiosi si sono cimentati nello stipulare le proprie ipotesi sul trasporto e soprattutto sulla sua messa in opera senza giungere ad un univoca conclusione. Si è proceduto poi alla loro schematizzazione in filoni principali senza tralasciare una propria opinione valutandone i pro e i contro anche in base alle conoscenze attuali. Si sono confrontati metodi di trasporto dei monoliti, senza tralasciare l’analisi delle macchine da cantiere dell’epoca a supporto delle ipotesi proposte. Da ultimo mi sono soffermato sul significato semantico delle dentellature di sommità della copertura, o modiglioni: anche per questi elementi vi sono stati e mi auguro ci saranno numerosi dibattiti sul loro aspetto simbolico o quantomeno funzionale. Durante la stesura della è scaturito anche un interessante confronto di idee che testimonia quanto la questione sia ancora articolata ed interessante. Si apre quindi a suggerimenti per spunti futuri specialmente per quanto riguarda indagini diagnostiche strumentali sulla cupola e sulla sua crepa. Mi auguro che raccogliendo e analizzando le principali ipotesi si possa proseguire questo filone investigativo.

Development of an antigen-driven colitis model to study presentation of antigens by antigen presenting cells to T cells

Inflammatory bowel disease (IBD) is a chronic inflammation which affects the gastrointestinal tract (GIT). One of the best ways to study the immunological mechanisms involved during the disease is the T cell transfer model of colitis. In this model, immunodeficient mice (RAG-/-recipients) are reconstituted with naive CD4+ T cells from healthy wild type hosts. This model allows examination of the earliest immunological events leading to disease and chronic inflammation, when the gut inflammation perpetuates but does not depend on a defined antigen. To study the potential role of antigen presenting cells (APCs) in the disease process, it is helpful to have an antigen-driven disease model, in which a defined commensal-derived antigen leads to colitis. An antigen driven-colitis model has hence been developed. In this model OT-II CD4+ T cells, that can recognize only specific epitopes in the OVA protein, are transferred into RAG-/- hosts challenged with CFP-OVA-expressing E. coli. This model allows the examination of interactions between APCs and T cells in the lamina propria.