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FRANCESCO RIVASI

PROFESSORE FUORI RUOLO Esterno
Dipartimento di Scienze Biomediche, Metaboliche e Neuroscienze sede Policlinico

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Pubblicazioni

2023 - Can immunohistochemistry improve the pathological diagnosis of placenta accreta spectrum (PAS) disorders? [Articolo su rivista]
Losi, Lorena; Botticelli, Laura; Mancini, Luciano; Negro, Rosa; Hanspeter, Esther; Dematté, Eva; Grandi, Giovanni; Facchinetti, Fabio; Veneziano, Micaela; Malagoli, Claudia; Masini, Meris; Fabbiani, Luca; Rivasi, Francesco
abstract

Purpose: The term of placenta accreta spectrum (PAS) disorder includes all grades of abnormal placentation. It is crucial for pathologist provide standardized diagnostic assessment to evaluate the outcome of management strategies. Moreover, a correct and safe diagnosis is useful in the medico-legal field when it becomes difficult for the gynecologist to demonstrate the suitability and legitimacy of demolitive treatment. The purposes of our study were: (1) to assess histopathologic features according to the recent guidelines; (2) to determine if immunohistochemistry can be useful to identify extravillous trophoblast (EVT) and to measure the depth of infiltration into the myometrium to improve the diagnosis of PAS. Methods: The retrospective study was conducted on 30 cases of gravid hysterectomy with histopathologic diagnosis of PAS. To identify the depth of EVT, immunohistochemical stainings were performed using anti MNF116 (cytokeratins 5, 6, 8, 17, 19), actin-SM, HPL (Human Placental Lactogen), vimentin and GATA3 antibodies. Results: Our cases were graded based on the degree of invasion of the myometrium. Ten were grade 1 (33.3%), 12 grade 2 (40%) and 8 grade 3A (26.7%). EVT invasion was best seen and evident by double immunostainings with actin-SM and cytokeratins, actin-SM and HPL, actin-SM and GATA3. Conclusion: The role of pathologist is decisive to determine the different grades of PAS. A better understanding of the depth of myometrial invasion can be achieved by the use of immunohistochemistry affording an important tool to obtain reproducible grading of PAS. This purpose is crucial in the setting of postoperative quality reviews and particularly in the forensic medicine field.

2016 - Promoter Methylation and Down-regulated Expression of the TBX15 Gene in Ovarian Carcinoma [Articolo su rivista]
Gozzi, Gaia; Chelbi, Sonia T; Manni, Paola; Alberti, Loredana; Fonda, Sergio; Saponaro, Sara; Fabbiani, Luca; Rivasi, Francesco; Benhattar, Jean; Losi, Lorena
abstract

TBX15 is a gene involved in the development of mesodermal derivatives. As the ovaries and the female reproductive system are of mesodermal origin, the aim of the present study was to determine the methylation status of the TBX15 gene promoter and the expression levels of TBX15 in ovarian carcinoma, which is the most lethal and aggressive type of gynecological tumor, in order to determine the role of TBX15 in the pathogenesis of ovarian carcinoma. This alteration could be used to predict tumor development, progression, recurrence and therapeutic effects. The study was conducted on 80 epithelial ovarian carcinoma and 17 control cases (normal ovarian and tubal tissues). TBX15 promoter methylation was first determined by pyrosequencing following bisulfite modification, then by cloning and sequencing, in order to obtain information about the epigenetic haplotype. Immunohistochemical analysis was performed to evaluate the correlation between the methylation and protein expression levels. Data revealed a statistically significant increase of the TBX15 promoter region methylation in 82% of the tumor samples and in various histological subtypes. Immunohistochemistry showed an inverse correlation between methylation levels and the expression of the TBX15 protein. Furthermore, numerous tumor samples displayed varying degrees of intratumor heterogeneity. Thus, the present study determined that ovarian carcinoma typically expresses low levels of TBX15 protein, predominantly due to an epigenetic mechanism. This may have a role in the pathogenesis of ovarian carcinoma independent of the histological subtype.

2014 - Suppression of invasion and metastasis of triple-negative breast cancer lines by pharmacological or genetic inhibition of slug activity [Articolo su rivista]
Ferrari Amorotti, Giovanna; Chiodoni, Claudia; Shen, Fei; Cattelani, Sara; Soliera, Angela Rachele; Manzotti, Gloria; Grisendi, Giulia; Dominici, Massimo; Rivasi, Francesco; Colombo, Mario Paolo; Fatatis, Alessandro; Calabretta, Bruno
abstract

Most triple-negative breast cancers (TNBCs) exhibit gene expression patterns associated with epithelial-to-mesenchymal transition (EMT), a feature that correlates with a propensity for metastatic spread. Overexpression of the EMT regulator Slug is detected in basal and mesenchymal-type TNBCs and is associated with reduced E-cadherin expression and aggressive disease. The effects of Slug depend, in part, on the interaction of its N-terminal SNAG repressor domain with the chromatin-modifying protein lysine demethylase 1 (LSD1); thus, we investigated whether tranylcypromine [also known as trans-2-phenylcyclopropylamine hydrochloride (PCPA) or Parnate], an inhibitor of LSD1 that blocks its interaction with Slug, suppresses the migration, invasion, and metastatic spread of TNBC cell lines. We show here that PCPA treatment induces the expression of E-cadherin and other epithelial markers and markedly suppresses migration and invasion of TNBC cell lines MDA-MB-231 and BT-549. These effects were phenocopied by Slug or LSD1 silencing. In two models of orthotopic breast cancer, PCPA treatment reduced local tumor growth and the number of lung metastases. In mice injected directly in the blood circulation with MDA-MB-231 cells, PCPA treatment or Slug silencing markedly inhibited bone metastases but had no effect on lung infiltration. Thus, blocking Slug activity may suppress the metastatic spread of TNBC and, perhaps, specifically inhibit homing/colonization to the bone.

2013 - Fetal bacterial infections in antepartum stillbirth: a case series [Articolo su rivista]
Monari, Francesca; Gabrielli, L; Gargano, Giuseppe; Annessi, Eleonora; Ferrari, Francesca; Rivasi, Francesco; Facchinetti, Fabio
abstract

OBJECTIVES: This study aims to assess the frequency of fetal bacterial infections in stillbirth (SB) and to evaluate the best samples for the diagnosis of infection-related SB. STUDY DESIGN: Consecutive cases of antepartum SB were enrolled. Vaginal and placental swabs, as well as heart blood cultures and surface swabs from the neonate, were collected. Histological examinations were performed by the same examiner. Immunohistochemistry for leukocyte common antigen was performed in the placenta and fetus. Each case was discussed in a multidisciplinary audit. RESULTS: One hundred and nine cases were enrolled. Fetal blood cultures were positive in 20/95 cases (21%). Significant histological findings in the placenta/cord and in at least one fetal organ were observed in 8 cases of them (4 Group B Streptococcus GBS, 2 Listeria monocytogenes, 1 Coagulase negative Staphylococcus, 1 Pseudomonas aeruginosa). Neither tissue damage nor inflammatory infiltrate was found in the 12 remnant cases. Funisitis while not histological chorioamnionitis was associated with microbiological findings. Positive findings in maternal/placental/fetal swabs occurred in 18-32% of cases with both negative fetal blood cultures and histopathological findings. With the exception of GBS, no other bacteria agent could be detected by any of the swabs. CONCLUSIONS: Eight cases (8.4%) fulfilled both microbiological and histology criteria allowing the diagnosis of SB-related fetal infection demonstrating that search for infections is essential in SB evaluation. Fetal blood culture, placenta swab for GBS and search for histological funisitis are mandatory actions within the SB work-up in order to guide pathology examination and reach clinical conclusions.

2012 - Can leptin-derived sequence-modified nanoparticles be suitable tools for brain delivery? [Articolo su rivista]
Tosi, Giovanni; Badiali, Luca; Ruozi, Barbara; Vergoni, Anna Valeria; Bondioli, Lucia; Ferrari, Anna; Rivasi, Francesco; Forni, Flavio; Vandelli, Maria Angela
abstract

Aim: In order to increase the knowledge on the use of the nanoparticles (Np) in the brain targeting, this paper describes the conjugation of the sequence 12-32 (g21) of Leptin (Lp) to poly-lactide-co-glycolide (PLGA) Np. The capability of these modified Np to reach the brain was evaluated in rats after i.v. administration.Materials and Methods: The g21 was linked on the surface of Np labeled with tetramethylrhodamine (TRM) by means of the Avidin-Biotin technology. The g21 labeled Np were injected into the tail vein of rats and, after animal sacrifice, the brain localization was evaluated by confocal microscopy, fluorescence microscopy and electron microscopy. Studies to evaluate the biodistribution of the g21 modified Np in comparison to the un-modified Np were also carried out. Moreover, to confirm the absence of any anorectic effect of g21 linked on the surface of Np, appropriate studies were assess in the rats.Results: After i.v. administration, the g21 modified Np were able to cross the BBB and to enter the brain parenchyma. The biodistribution studies of both un-modified and modified Np pointed out an uptake at liver and spleen level, whereas only the g21 modified Np showed brain localization. The food-intake experiments pointed out that the i.v. administration of g21 conjugated to the Np surface did not produce any anorectic effect in the rats.Conclusion: g21-modified Np were able to cross the BBB. This new modified Np could be effectively considered as useful carrier systems for brain drug delivery.

2012 - Chronic/relapsing lymphadenopathy associated with HHV-6B infection: a new benign clinico-pathologic entity occurring in immunocompetent individuals [Abstract in Rivista]
Forghieri, Fabio; Potenza, Leonardo; Barozzi, Patrizia; Vallerini, Daniela; Riva, Giovanni; Zanetti, E; Quadrelli, C; Morselli, M; Leonardi, G; Maccaferri, M; Paolini, Ambra; Coluccio, Valeria; Colaci, Elisabetta; Pedrazzi, Letizia; Fantuzzi, Valeria; Bigliardi, Sara; Soci, Francesco; Bonacorsi, G; Zaldini, P; Rossi, G; Milani, M; Rivasi, Francesco; Gennari, W; Pecorari, M; Grottola, Antonella; Tagliazucchi, S; Rumpianesi, F; Mattioli, F; Presutti, Livio; Franzoni, Chiara; Gelmini, Roberta; Saviano, Massimo; Cermelli, Claudio; Marasca, Roberto; Narni, Franco; Luppi, Mario
abstract

Background. HHV-6 DNA sequences were disclosed in lymph node (LN) tis- sues of several patients with lymphoid malignancies, but a direct major role of HHV-6 in lymphoid malignant transformation has so far not been confirmed. In contrast, active HHV-6 infection has been associated to either infectious mononucleosis-like syndrome or acute lymphadenitis occurring in febrilepatients with systemic symptoms, or to Rosai-Dorfman disease in which viral antigens have been detected by immunohistochimical (IHC) analyses in both histiocytes and follicular dendritic cells (FDCs). Methods. We have retrospec- tively analyzed clinical and pathological data of 365 adult patients, consecutive- ly observed at our Institution over a period of 5 years (2006-2010), because of enlarged superficial lymph nodes and subsequently undergoing lymphadenec- tomy. In the benign/reactive cases in which well-recognized etiologies have been excluded, an involvement of HHV-6 active infection or reactivation was investigated by molecular and immunohistochemical examinations. Results. Malignant disorders, namely malignant lymphoproliferative disorders or solid cancer metastases, were found in 227 cases (62%), whereas in 138 cases (38%) benign/reactive pictures were documented on lymph node examination. Among these latter cases, a well-recognized etiology was demonstrated in 84 patients (61%), while in 54 cases (39%), a well-defined non-malignant reactive/infectious cause could not be documented. Immunohistochemical analyses resulted negative for both HHV-6A and HHV-6B in 38 of these latter lymph nodes (70%). In 7 patients (13%), a scattered, scanty and aspecific pos- itivity for HHV-6B late protein was documented in rare interfollicular plasma cells and histiocytes. Surprisingly, in 9 patients (17%), immunohistochemical analyses showed HHV-6B positive staining of FDCs, together with scattered positivity of interfollicular cells. These 9 HIV-negative adult patients (median age 42 years, range 18-76 years), with either localized or generalized LAP, were observed for a median follow-up of 38 months (range 28-166). Of note, six of them presented with recurrent LAP (one to 3 recurrences), without evolving into lymphoma. A common LN histological pattern at presentation showed florid fol- licular hyperplasia with concurrent mild paracortical expansion. Three cases also showed features consistent with PTGC. Constitutional symptoms were absent in all patients. The IHC reactions for both HHV-6A and HHV-6B, per- formed on further control cases, represented by 131 LN tissues from patients with either benign LAP induced by other known etiologies or lymphoma, were invariably negative. Serology was positive for both IgM and IgG with high avid- ity suggesting viral reactivation/reinfection. However, the molecular analyses failed to detect HHV-6 viremias in cell-free-serum samples of all the 9 patients with positive HHV-6B IHC staining, while positivity for HHV-6B DNA was dis- closed by PCR analyses in 7 out of the 7 LN tissues studied. Conclusions. We show for the first time that local reactivation/infection of HHV-6B should be con- sidered among the possible causes of chronic/relapsing benign LAP in immuno- competent individuals. IHC is the method of choice for investigating the pres- ence of HHV-6 infection in such cases. HHV-6B may indirectly modulate and trigger the proliferation of lymphocytes, by locally affecting FDCs and LN microenvironment. FDCs may indeed be involved in presenting HHV-6B anti- gens to other immune cells, mainly cortical B lymphocytes.

2012 - MUC5AC, cytokeratin 20 and HER2 expression and K-RAS mutations within mucinogenic growth in congenital pulmonary airway malformations [Articolo su rivista]
Rossi, G; Gasser, B; Sartori, G; Migaldi, Mario; Costantini, M; Mengoli, Mc; Piccioli, S; Cavazza, A; Rivasi, Francesco
abstract

Histopathology MUC5AC, cytokeratin 20 and HER2 expression and K-RAS mutations within mucinogenic growth in congenital pulmonary airway malformations Aims:  To analyse the expression of several mucins (MUC1, MUC2, MUC3, MUC5AC and MUC6), epidermal growth factor receptor (EGFR), v-erb-b2 erythroblastic leukaemia viral oncogene homologue 2 (HER2), thyroid transcription factor-1 (TTF-1), caudal type homeobox 2 (CDX2) and cytokeratin 20 (CK20), and the presence of mutations of EGFR, KRAS and HER2 in congenital pulmonary airway malformations (CPAM). Methods and results:  Forty-one cases of CPAM and six pulmonary sequestrations were included. TTF-1 expression was observed in all cases but was not seen in mucinogenic growths in CPAM. CDX2 expression was completely negative. MUC1 expression was noted in 12 (29%) CPAM and in 33% sequestrations. MUC5AC was noted in only five cases (26%) by immunohistochemistry and was found in the mucinogenic proliferations of type 1 CPAM. No immunolabelling was noted for the other mucins. EGFR was expressed variably in almost all cases, while HER2 and CK20 was seen exclusively in the mucinogenic proliferations. All mucinous growths were characterized by KRAS mutations. No EGFR and HER2 gene alterations were identified. Conclusions:  KRAS mutations and MUC5AC, CK20 and HER2 expression was seen in all mucinogenic proliferations, supporting the neoplastic nature of these cytologically bland growths. These findings emphasize the importance of complete surgical resection of such lesions.

2011 - A case of human conjunctival dirofilariosis by Dirofilaria immitis in Italy. [Articolo su rivista]
F. O., Avellis; L. H., Kramer; P., Mora; A., Bartolino; P., Benedetti; Rivasi, Francesco
abstract

This short communication describes a case of human conjunctival dirofilariosis by Dirofilaria immitis. A 51-year-old man from the Emilia-Romagna region of northeastern Italy referred for ocular foreign body sensation in his right eye. A slight swelling of the bulbar conjunctiva was observed. A live, whitish, 10-cm-long nematode was extracted from the subconjunctival space. Histology revealed typical features of a filarioid nematode belonging to the genus Dirofilaria sp. Molecular analysis with polymerase chain reaction confirmed that the extracted nematode was a male of D. immitis. The removal of the parasite leads to complete resolution of symptoms. Ocular human dirofilariosis caused by infection with the filarioid nematode D. immitis is extremely rare, but should be considered in humans living in Italian endemic areas.

2011 - Brain targeting by engineered nanoparticles [Relazione in Atti di Convegno]
Tosi, Giovanni; A., Grabrucker; L., Bondioli; Ruozi, Barbara; Zoli, Michele; Vilella, Antonietta; Forni, Flavio; Rivasi, Francesco; Vandelli, Maria Angela
abstract

In the last years, the application of "nanotechnology“ to the field of “medicine” surely represented the most innovative strategy to cope with difficult-to-treat diseases. Thus, nanotech-based drug delivery and targeting are nowadays some of the hottest topics in science and in particular in Neuroscience. The results of our research, based on in vitro and in vivo preclinical tests strongly indicate that specifically engineered nanoparticles, made of poly-lactide-co-glycolide (PLGA) polymer, are able to cross the Blood-brain barrier (BBB) and to deliver a variety of drugs or active molecules inside the Central Nervous System (CNS). A recent report from the World Health Organization (WHO) emphasizes that neurological disorders (brain injuries, neuroinfections, multiple sclerosis, epilepsy, stroke, Alzheimer and Parkinson disease) affect up to one billion people worldwide [World Health Organization, Neurological disorders : public health challenger, Geneva, 2006]. Until now, only 2% of the overall drugs are able to enter the brain as the BBB restricts the diffusion of substances from blood to the brain. Thus, one of the challenges of pharmaceutical research nowadays is to discover tools enabling an effective and efficacious delivery of drugs into the CNS. To improve the efficacy of drugs, a possible answer could be the nanomedicine approach, and its application on neuroscience (neuro-nanomedicine). Thereby, the perspective of introducing a tool, capable of directed delivery of every drug into the brain, is undoubtedly an attractive goal for researchers and practitioners. To that end, neuro -nanomedicine exploits pharmaceutical technology, using well-known nanocarriers such as liposomes and polymeric nanoparticles (NPs). These nanosystems, ranging from 100 nm to 250 nm, are able to protect loaded drugs from being metabolised and eliminated, to assure the controlled release of the embedded drugs and to target specific cell population if specifically engineered.To achieve this goal we planned, create and test specifically engineering the NPs surface able to take advantage of the BBB crossing pathways, such as endocytosis or transcytosis. We applied this approach modifying FDA-approved biodegradable NPs with two different peptides to produce highly selective nanosystems able to enter the brain after i.v. administration in the rodents model. The administration of engineered-NPs allowed a variety of drugs to cross the BBB at a rate of 15-20% of the injected dose. The mechanism of BBB crossing of those NPs were elucidated by means of several in vitro and in vivo experiments as the safety of NPs on neuron cell colture was proven. The potential impact of such nanotech-based innovations relies on the possible changes in treatments and cures of the most difficult-to-treat neurological diseases, opening the pave to a new vista on the future trend in medicine, which should strengthen the relationship between different field of research (from clinician-based to chemistry, nanotechnology, biology and pre-clinical study) becoming more and more translational and interdisciplinar.

2011 - Brain targeting by engineered nanoparticles: in vivo and in vitro evidences [Abstract in Atti di Convegno]
Tosi, Giovanni; A., Grabrucker; L., Bondioli; Ruozi, Barbara; Zoli, Michele; Vilella, Antonietta; Forni, Flavio; Rivasi, Francesco; Vandelli, Maria Angela
abstract

In the last years, the application of "nanotechnology“ to the field of “medicine” surely represented the most innovative strategy to cope with diseases and could be named as nanomedicine, which is mostly applied to difficult-to-treat diseases. In this field of research, the most important goal to be reached is an increase in selectivity and specificity of drug-action. Several results with stimulating findings in preclinical or clinical phases have been obtained using nanocarriers delivering agents to targeted pathologies, and among them, it is known that neuro-pathologies represent a stimulating issue. In fact, the pharmaceutical treatment of Central Nervous System (CNS) disorders is the second largest area of therapy, following cardiovascular diseases. Nowadays, non-invasive drug delivery systems for CNS are actively studied. The nano-technological approach consists of the use of nanosystems (colloidal carriers), which could be polymer-based (nanoparticles, Np) or solid lipid material made (solid lipid nanoparticles, SLNp) and lipid-based (liposomes, LP). In fact, the development of these new delivery systems started with the discovery that properly surface-engineered colloidal vectors, with a diameter around 200 nm, are able to cross the BBB without causing apparent damage, and to deliver drugs or genetic materials into the brain. During this talk, an overview will be presented considering the most recent literature results of nanomedicine applied to brain diseases, focusing in particular on peptide-decorated nanosystems able to target the CNS.In vitro and in vivo experiments allowed to establish a pathway through which engineered NPs can cross the BBB and showed the possible NPs’ transport from cell to cell inside the CNS and the possible tropism of NPs for specific neuronal cell populations.References• A.M. Grabrucker, C. C. Garner, T.M. Boeckers, L. Bondioli, B. Ruozi, F.Forni, M.A. Vandelli, G.Tosi , Development of novel Zn2+ loaded nanoparticles designed for cell-type targeted drug release in CNS neurons: in vitro evidences. PLOS ONE, 2011, Vol 6, e17851.• G. Tosi, R.A. Fano, L. Badiali, R. Benassi, F. Rivasi, B. Ruozi, F. Forni, M.A., Vandelli. Investigation on the mechanisms for Blood-Brain Barrier crossing of brain-targeted glycopeptides nanoparticles, Nanomedicine UK, 2011, 6(3), 423-436• G. Tosi, AV Vergoni, B. Ruozi, L. Bondioli, L. Badiali, F. Rivasi, L. Costantino, F. Forni, M.A. Vandelli, Sialic-acid and glycopeptides conjugated PLGA nanoparticles for Central Nervous System targeting: in vivo pharmacological evidence and biodistribution, Journal of Controlled Release, 2010,145, 49-57.

2011 - Dirofilarial infections in Europe [Articolo su rivista]
C., Genchi; L. H., Kramer; Rivasi, Francesco
abstract

Nematodes of the genus Dirofilaria are currently considered emerging agents of parasitic zoonoses in Europe. Climatic changes and an increase in the movement of reservoirs (mostly infected dogs) have caused an increase in the geographical range of these parasites from the traditionally endemic/hyperendemic southern regions, and the risk for human infection has increased. In the last several years, forecast models have predicted that current summer temperatures are sufficient to facilitate extrinsic incubation of Dirofilaria in many areas of Europe. The global warming projected by the Intergovernmental Panel on Climate Change suggests that warm summers suitable for Dirofilaria transmission in Europe will be the rule in the future decades, and if the actual trend of temperature increase continues, filarial infection should spread into previously infection-free areas. Dirofilaria repens is currently the filarial species that is most commonly reported as spreading from southern to northern areas. This article reviews the zoonotic aspects, effects of climate, and other global drivers on Dirofilaria infections in Europe and the possible implications on the transmission and control of these mosquito-borne nematodes.

2011 - Down-regulation of μ-protocadherin expression is a common event in colorectal carcinogenesis [Articolo su rivista]
Losi, Lorena; Parenti, Sandra; Fabrizio, Ferrarini; Rivasi, Francesco; Margherita, Gavioli; Gianni, Natalini; Ferrari, Sergio; Grande, Alexis
abstract

We have previously reported that treatment of colorectal cancer cells with mesalazine results in the up-regulated expression of a novel member of the cadherin protein superfamily, named μ-protocadherin, which is able to sequester β-catenin on plasmatic membrane of treated cells inhibiting its proliferation signalling pathway. This finding suggests that μ-protocadherin could exert an oncosuppressive effect on colorectal epithelium. The purpose of our study was to assess whether μ-protocadherin expression is down-regulated during colorectal carcinogenesis. This issue was addressed by analyzing the messenger RNA and protein expression of μ-protocadherin in normal and tumor colorectal cell samples using a combination of quantitative real-time polymerase chain reaction, microarray analysis, and immunohistochemical examination. To better contextualize the role played by μ-protocadherin in the pathogenesis of colorectal cancer, this last assay was also extended to β-catenin, E-cadherin, and Ki-67 proteins. The results obtained evidenced that (1) levels of μ-protocadherin transcript were down-regulated in all the analyzed colorectal cancer samples as compared with normal mucosa; (2) expression of μ-protocadherin protein was completely lost in most analyzed colorectal cancer samples (71%); (3) μ-protocadherin retains β-catenin on the plasmatic membrane of normal colon enterocytes, which implies that β-catenin is released from this site and translocated to the nucleus in colorectal cancer cells. Our data consequently suggest that down-regulation of μ-protocadherin expression is a common event in colorectal carcinogenesis and might therefore play an important role in this pathologic process.

2011 - Heavy metals nanoparticles in fetal kidney and liver tissues [Articolo su rivista]
Gatti, Antonietta; Bosco, P; Rivasi, Francesco; Bianca, S; Ettore, G; Gaetti, L; Montanari, S; Bartoloni, G; Gazzolo, D.
abstract

The proliferation of the nanotechnologies with the production of engineered nanoparticles presents a dilemma to regulators regarding hazard identification mostly for human health. We investigated the presence of inorganic micro and nanosized contamination in fetal liver and kidney tissues by Field Emission Gun-Environmental Scanning Electron Microscope (FEGESEM) innovative observations. An observational study in 16 fetuses, complicated (n=8) or not (n=8) by neural tube defects, whose mothers obtained the authorization for abortion between 21-23 weeks of gestation was carried out. Heavy metals concentrations in maternal blood were undetectable. FEGESEM assessment showed particles of iron, silicon, aluminum and magnesium in different tissues analyzed. The mean size and the number of the foreign bodies detected in kidney and liver tissues were higher in NTD fetuses as well as the number of total particles (P < 0.05, for all). The present study shows first the presence of xenobiotic, nanoscaled contamination, not detectable in maternal blood in fetuses. Data are suggestive and open-up a new clue for further investigations to elucidate the relationship between pollution at nanoscale stage and multiorgan damage.

2011 - Investigation on Mechanisms of Glycopeptide Nanoparticles for Drug Delivery across the Blood-Brain Barrier [Articolo su rivista]
Tosi, Giovanni; Fano, Rita Adriana; Bondioli, Lucia; Badiali, Luca; Benassi, Rois; Rivasi, Francesco; Ruozi, Barbara; Forni, Flavio; Vandelli, Maria Angela
abstract

AimsNano-neuroscience, based on the use polymeric nanoparticles (NPs), is representing an emerging field of research for achieving an effective therapy for neurodegenerative diseases. In particular, poly-lactide-co-glycolide (PLGA) glyco-heptapetide-conjugated NPs (g7-NPs) were shown to be able to cross the Blood-Brain Barrier (BBB). However, the in vivo mechanisms of the BBB crossing of this kind of NPs has not been investigated until now. This paper aimed to develop a deep investigation on the mechanism of BBB crossing of the modified NPs.Materials and MethodsLoperamide (LOP) and Rhodamine-123 (Rh-123) (model drugs unable to cross the BBB) were loaded into NPs, composed of a mixture of poly-lactide-co-glycolide (PLGA), differently modified with g7 or with a random sequence of the same aminoamids (random-g7). To study brain targeting of these model drugs, loaded NPs were administered via tail vein in rats in order to perform both pharmacological studies and biodistribution analysis along with fluorescent, confocal and electron microscopy analysis, in order to achieve NPs BBB crossing mechanism. Computational analysis on the conformation of the g7- and random-g7-NPs of the NPs surface was also developed. Results Only LOP delivered to the brain with g7-NPs created a high central analgesia, corresponding to the 14% of the injected dose, data confirmed by biodistribution studies. Electron photomicrographs showed the ability of g7-NPs in crossing the BBB as evidenced by several endocytotic vesicles and macropinocytotic processes. The computational analysis on g7 and random-g7 showed a different conformation (linear versus globular), thus suggesting a different interaction with the BBB. ConclusionTaken together, these evidences suggested that g7-NPs BBB crossing is owing to a multiple-pathway, mainly membrane-membrane interaction and macropinocytosis-like mechanisms. The results of the computational analysis showed the Biousian structure of the g7 peptide, on the contrary of random-g7 peptide (globular conformation), suggesting that this difference is pivotal in explaining the BBB crossing and to allow to hypothesize the mechanism of BBB crossing by g7-NPs.

2011 - Lambert-Eaton myasthenic syndrome associated with intravascular uterine leiomyoma. [Articolo su rivista]
Galassi, G; Ariatti, A; Agnoletto, V; Rivasi, Francesco
abstract

Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune neurologic disease with impaired transmission across neuromuscular junction, and . LEMS is thought to be caused by antibodies directed against presynaptic P/Q-type voltage-gated calcium channels (VGCC), most likely associated with small cell lung cancers (SCLC) , and . LEMS shares clinical features with myasthenia gravis; patients usually experience cranial, limb fluctuating weakness and autonomic signs , and . Neurologic symptoms precede or concur with cancer diagnosis , and . This 40 year old woman experienced (September 2006) dry mouth, fluctuating fatiguability.

2011 - Nanoparticles and the BBB crossing: in vivo and in vitro upcomings [Relazione in Atti di Convegno]
Tosi, Giovanni; Bondioli, Lucia; Ruozi, Barbara; Andreas, Grabrucker; Vilella, Antonietta; Zoli, Michele; Rivasi, Francesco; Vandelli, Maria Angela; Forni, Flavio
abstract

In the last years, the application of "nanotechnology “to the field of “medicine” surely represented the most innovative strategy to cop_20e with diseases and it could be named as nanomedicine applied to difficult-to-treat diseases. As known, in this field of research, the most important goal to be reached is an increase in selectivity and specificity of drug action. Several results with stimulating findings in preclinical or clinical phases have been reached by using nanocarriers, delivering agents to targeted pathologies, and among them, it is known that neuro-pathologies represent a stimulating issue. In fact, the pharmaceutical treatment of Central Nervous System (CNS) disorders is the second largest area of therapy, following cardiovascular diseases. Nowadays, non-invasive drug delivery systems for CNS are actively studied. In fact, the development of new delivery systems (nanoparticles and liposomes) started with the discovery that properly surface-engineered colloidal vectors, with a diameter around 200 nm, were shown to be able to cross the Blood-Brain Barrier without apparent damage, and to deliver drugs or genetic materials into the brain. During this talk, an overview will be presented considering the most recent literature results of nanomedicine applied to brain diseases, carried out with all the most popular kinds of nanoparticulate systems, focusing in particular on immune-nanoparticles and peptide-decorated nanosystems able to target the CNS, with in vivo and in vitro evidences investigating the pathway for BBB crossing and CNS localization of engineered nanoparticles. The brain localization and the multi-modal pathways for BBB crossing highlighted the endocytosis as preferential pathway; moveover, in vitro test on hippocampal neurons showed the presence of cell-to-cell transport of nanoparticles.

2011 - Nanoparticles for brain delivery of drugs: in vivo experiments and mechanism of BBB crossing [Articolo su rivista]
Tosi, Giovanni; Fano, Rita Adriana; Badiali, Luca; Bondioli, Lucia; Ruozi, Barbara; Vergoni, Anna Valeria; Rivasi, Francesco; Benassi, Rois; Vandelli, Maria Angela; Forni, Flavio
abstract

Specific ligands on the surface allowed the Np to cross the Blood-Brain Barrier (BBB) carrying model drugs within the brain district after their i.v. administration in experimental animals. It is known that sialic acid receptors are present in several organs, including in the brain parenchyma. Thus, we prepared PLGA NPs surface modified with a BBB-penetrating peptide (simil-opioid peptide) for BBB crossing and with a sialic acid residue (SA) for the interaction with brain receptors. This double coverage could allow to obtain novel targeted NPs with a prolonged residence within the brain parenchyma, thus letting to reach a long-lasting brain delivery of drugs. The central analgesic activity of Loperamide (opioid drug, unable to cross the BBB) loaded in these novel NPs was evaluated in order to point out the capability of the NPs to reach and to remain in the brain. The results showed that the pharmacological effect induced by loaded NPs administration remained significant over 24 hrs. Using confocal and fluorescent microscopy, the novel NPs were localized within the tissue parenchyma (brain, kidney, liver, spleen and lung). Finally, the biodistribution studies showed a localization of the 6% of the injected dose into the CNS over a prolonged time (24 hrs). Notwithstanding an increased accumulation of SA-covered NPs in those organs showing SA-receptors (liver, kidney, lung), the pharmacological and biodistribution results are proofs of the ability of double targeted NPs to enter the brain allowing the drug to be released over a prolonged time. Moreover, electron microscopy of brain sections after iv administration of modified NPs, allowed us to hypothesize a multiple-pathway mechanism of BBB crossing of modified NPs. NPs surface interaction with BBB membrane without a clear involvement of specific receptors, but possibly based on “biousian conformation” of the surface of NPs, along with ruffles of the membrane produced near to modified-NPs, seemed to mediate a BBB crossing process based on endocytosis

2011 - Peritoneal keratin granulomas: cytohistological correlation in a case of endometrial adenocarcinomawith squamous differentiation. [Articolo su rivista]
Rivasi, Francesco; Palicelli, A.
abstract

Granulomatous peritoneal inflammationcan be due to many aetiological factors, mostly nonneoplastic(i.e. bacterial and fungal infections, parasiticinfestations, sarcoidosis, endometriosis, Crohnsdisease, foreign body reaction due to surgical material,plant material after barium enema examination,vegetable fragments from intestinal perforation, andvernix caseosa derived from amniotic fluid) but rarelysecondary to a neoplastic process.1–3 However, peritonealkeratin granulomas (PKG) have been found tobe associated with endometrial and ⁄ or ovarian adenocarcinomawith squamous differentiation,1–6 cervicalsquamous cell carcinoma (particularly followingradiation therapy),1 endometrial atypical polypoidadenomyoma with squamous morulae3 or brokenovarian dermoid cysts.1–3 We report a case of PKGvery similar to that reported by Chen,1 in a patientwith endometrial adenocarcinoma with squamousdifferentiation, and can find no other reports investigatingthe cytohistological correlation of these raregranulomatous lesions.

2010 - Contrast-enhanced MRI and PET-CT in the evaluation of patients with suspected local recurrence of rectal carcinoma. [Articolo su rivista]
Fiocchi, F; Iotti, V; Ligabue, Guido; Pecchi, A; Luppi, G; Bagni, B; Rivasi, Francesco; Torricelli, Pietro
abstract

This study aimed to evaluate the role of contrast-enhanced magnetic resonance imaging (MRI) and positron emission tomography-computed tomography (PET-CT) in the assessment of local recurrence of rectal cancer.Among 200 patients scheduled for CT follow-up, 60 (48 low risk; 12 high risk) were selected due to CT findings suspicious for or suggestive of local recurrence. Patients underwent contrast-enhanced MRI and PET-CT within 2 weeks. Biopsy was considered the gold standard in 39 cases and follow-up at 6 and 12 months in the remaining 21.Local recurrence was confirmed by histology in 15 cases (7 low risk; 8 high risk) and was excluded in 21 cases by long-term follow-up and in 24 by histology. Sensitivity, specificity, positive and negative predictive value and accuracy were 86.7%, 68.9%, 48.1%, 93.9% and 73.3% for contrast-enhanced MRI and 93.3%, 68.9%, 50%, 96.9% and 75% for PET-CT.Contrast-enhanced MRI and PET-CT can help in the detection of local recurrence of rectal cancer, even though their roles in early detection remains debatable, as the value of these techniques in current surveillance protocols is still to be defined.

2010 - FATAL ASPERGILLUS FLAVUS INFECTION IN A NEONATE [Articolo su rivista]
Roncati, Luca; Barbolini, Giuseppe; Fano, Rita Adriana; Rivasi, Francesco
abstract

Aspergillosis is an uncommon perinatal infection diagnosed with increasing frequency in recent years. We report a premature infant who required both nutrition and ventilation artificially assisted and developed a disseminated invasive nosocomial infection from Aspergillus flavus. Autopsy revealed marked hypotrophy of the thymus and ultisystem invasive aspergillosis chiefly involving the vascular and alimentary systems and also the respiratory tract, the central nervous system, and the skin. From what we know, this is the first case of the literature with a misleading initial clinical presentation involving the alimentary tract (hepatomegaly, ingravescent cholestatic icterus) and evolving in ntestinal occlusion.

2010 - Massive ovarian edema in a prepubertal girl without signs of virilization or early puberty [Articolo su rivista]
Repetto, P.; Ceccarelli, P. L.; Bianchini, M. A.; Mordenti, M.; Durante, V.; Rivasi, Francesco; Cacciari, Alfredo
abstract

Massive ovarian edema is a rare cause of ovarian enlargement in young women. This article describes the case in a nine-year-old girl without signs of virilization or early puberty. The patient underwent laparotomy and a right oophorectomy was performed. The final pathology was massive ovarian edema. Awareness of this rare and benign lesion in young women and pediatric patients may allow a conservative management avoiding oophorectomy in some cases.

2010 - Nanoparticles for brain delivery of drugs: in vivo experiments andmechanism of BBB crossing [Relazione in Atti di Convegno]
Tosi, Giovanni; Fano, Rita Adriana; Badiali, Luca; Bondioli, Lucia; Ruozi, Barbara; Vergoni, Anna Valeria; Rivasi, Francesco; Benassi, Rois; Vandelli, Maria Angela; Forni, Flavio
abstract

Specific ligands on the surface allowed the Np to cross the Blood-Brain Barrier (BBB) carrying model drugs within the brain district after their i.v. administration in experimental animals. It is known that sialic acid receptors are present in several organs, including in the brain parenchyma. Thus, we prepared PLGA Np surface modified with a BBB-penetrating peptide (simil-opioid peptide) for BBB crossing and with a sialic acid residue (SA) for the interaction with brain receptors. This double coverage could allow to obtain novel targeted Np with a prolonged residence within the brain parenchyma, thus letting to reach a long-lasting brain delivery of drugs. The central analgesic activity of Loperamide (opioid drug, unable to cross the BBB) loaded in these novel Np was evaluated in order to point out the capability of the Np to reach and to remain in the brain. The results showed that the pharmacological effect induced by loaded Np administration remained significant over 24 hrs. Using confocal and fluorescent microscopy, the novel Np were localized within the tissue parenchyma (brain, kidney, liver, spleen and lung). Finally, the biodistribution studies showed a localization of the 6% of the injected dose into the CNS over a prolonged time (24 hrs). Notwithstanding an increased accumulation of SA-covered Np in those organs showing SA-receptors (liver, kidney, lung), the pharmacological and biodistribution results are proofs of the ability of double targeted Np to enter the brain allowing the drug to be released over a prolonged time. Moreover, electron microscopy of brain sections after iv administration of modified Np, allowed us to hypothesize a multiple-pathway mechanism of BBB crossing of modified Np. Np surface interaction with BBB membrane without a clear involvement of specific receptors, but possibly based on “biousian conformation” of the surface of Np, along with ruffles of the membrane produced near to modified-Np, seemed to mediate a BBB crossing process based on endocytosis.

2010 - Organising pneumonia mimicking invasive fungal disease in patients with leukaemia. [Articolo su rivista]
Forghieri, Fabio; Potenza, Leonardo; Morselli, M; Maccaferri, Monica; Pedrazzi, L; Barozzi, Patrizia; Vallerini, Daniela; Riva, Giovanni; Zanetti, Eleonora; Quadrelli, Chiara; Rossi, G; Rivasi, Francesco; Messino', M; Rumpianesi, F; Grottola, Antonella; Venturelli, C; Pecorari, M; Codeluppi, M; Torelli, Giuseppe; Luppi, Mario
abstract

Clinical charts from 63 consecutive highly immunocompromised haematologic patients presenting with pulmonary nodular lesions on CT scan, classified as either probable or possible invasive fungal disease (IFD) according to the revised EORTC/MSG classification, were retrospectively studied. Histopathological analysis of lung tissues, available for 23 patients, demonstrated proven IFD in 17 cases (14 invasive aspergillosis and 3 invasive zygomycosis), diffuse alveolar damage in one and organising pneumonia (OP) in five cases. In the OP cases, three of which have been defined as probable IFD according to EORTC/MSG classification, extensive immunohistochemical, molecular and immunological analyses for fungi were negative. Our case descriptions extend the notion that OP may be encountered as a distinct histopathological entity in pulmonary nodular lesions in patients with leukaemia with probable/possible IFD.

2010 - Peptide-engineered polylactide-co-glycolide (PLGA) nanoparticles for brain delivery of drugs: in vivo experiments and proof of concept [Relazione in Atti di Convegno]
Tosi, Giovanni; Fano, Rita Adriana; Badiali, Luca; Bondioli, Lucia; Ruozi, Barbara; Vergoni, Anna Valeria; Rivasi, Francesco; Benassi, Rois; Vandelli, Maria Angela; Forni, Flavio
abstract

Drug delivery to the Central Nervous System (CNS) represents a huge challenge for all neuroscientists owing to the presence of the Blood-Brain Barrier (BBB) hampering the influx to the brain of most of the drugs, enzymes, gene materials. Nanotechnology, based on polymeric nanoparticles (Np) and liposomes, could be an useful tool for the delivery of the drugs in the brain if they are planned for crossing the BBB. This goal can be achieved specifically engineering the Np surface in order to take advantage of the BBB crossing pathways, such as endocytosis or transcytosis. We applied this approach modifying polylactide-co-glycolide (PLGA) Np with two different peptides to produce highly selective nanosystems able to enter the brain after i.v. administration in the rats [Costantino L. et al. (2005). J Control Rel 108, 84-96; Tosi G. et al. (2007) J. Control Rel 122, 1-9]. The administration of decorated Np with a simil-opioid peptide (planned and synthesized in our laboratories) allows a variety of P-glycoprotein substrate to cross the BBB at a rate of 15-20% of the injected dose, as microscopy technique (confocal, fluorescent), biodistribution and pharmacological studies proved [Vergoni A.V. et al. (2009) Nanomedicine (NBM) 5, 369-377] These systems cross the BBB via an endocytic mechanism pointed out by an electron microscopy procedure (fig. 1). On the contrary, the Np decorated with a Leptin fragment should be able to take advantage of specific BBB-leptin receptors (Ob-R). In vivo experiments pointed out the efficacy of these leptin modified Np in the brain delivery and the trancytosis mechanism of the BBB crossing (fig. 2). Any anoretic effect of the Leptin-fragment covering the Np was exclude by food-intake experiments.Figure 1. Left: Electron microscopy image of multiple mechanisms of simil-opioid-Np interaction with BBB endothelial cells; Right: Fig. 2. Brain images after iv administration of Leptin-derived peptide- Np. Red spots are due to Np labeled with TRICT and blue-spots are brain nuclei with DAPI.

2010 - Polymeric nanoparticles for CNS drug delivery: strategies and perspectives [Relazione in Atti di Convegno]
Tosi, Giovanni; Bondioli, Lucia; Badiali, Luca; Ruozi, Barbara; Vergoni, Anna Valeria; Rivasi, Francesco; Vandelli, Maria Angela; Forni, Flavio
abstract

The application of nanotechnology to health raises high expectations for a more efficient and affordable healthcare. Even if several areas of medical care could benefit from the advantages that nanotechnology can offer, a selective CNS drug delivery and targeting could improve the therapy of brain diseases which have a tremendous negative impact not only on the patient himself but also on the whole society and linked social and insurance systems. Polymeric nanoparticles (Np) have been considered as strategic carriers for the brain delivery and targeting. Specific ligands on the surface allowed the Np to cross the Blood-Brain Barrier (BBB) carrying model drugs within the brain district after their i.v. administration in experimental animals. A new strategy for Np brain targeting by using a simil-opioid peptide−derived PLGA, obtaining Np showing both the ligands for CNS targeting and the marker of fluorescence on their surface was found (M-Np). After administration, the M-Np were found to be able to cross the BBB and the ability of these M-Np to act as drug carriers has been shown (Tosi et al., 2007). Moreover, the biodistribution of M-Np showed a localization into the CNS in a quantity (15% of the injected dose) about two orders of magnitude greater than that found with the other known Np drug carriers (Vergoni et al., 2009). Moreover, it is known that sialic acid receptors are present in several organs, including in the brain parenchyma. Thus, PLGA Np modified on their surface with a BBB-crossing ligand (simil-opioid peptide) and with a sialic acid residue (SA) were prepared (SA-M-Np). This double targeting (for BBB crossing and for the interaction with brain receptors) allowed to obtain novel targeted Np with a prolonged residence within the brain parenchyma, thus letting to reach a long-lasting brain delivery of drugs. Notwithstanding an increased accumulation of SA-covered Np in those organs showing SA-receptors (liver, kidney, lung), the pharmacological and biodistribution results are proofs of the ability of double-targeted Np to enter the brain allowing the drug to be released over a prolonged time. References•Tosi G. et al., Targeting the Central Nervous System. In vivo experiments with peptide derivatized nanoparticles loaded with Loperamide and Rhodamine 123, J. Control. Release 122 (2007) 1-9.•Vergoni AV et al., Nanoparticles as drug delivery agents specific for CNS: in vivo biodistribution. Nanomedicine: Nanotechnology, Biology and Medicine 5 (2009) 369-377.

2010 - Sialic acid and glycopeptides conjugated PLGA nanoparticles for central nervous system targeting: In vivo pharmacological evidence and biodistribution [Articolo su rivista]
Tosi, Giovanni; Vergoni, Anna Valeria; Ruozi, Barbara; Bondioli, Lucia; Badiali, Luca; Rivasi, Francesco; Costantino, Luca; Forni, Flavio; Vandelli, Maria Angela
abstract

Polymeric nanoparticles (Np) have been considered as strategic carriers for brain targeting. Specific ligands on the surface allowed the Np to cross the Blood-Brain Barrier (BBB) carrying model drugs within the brain district after their i.v. administration in experimental animals.It is known that sialic acid receptors are present in several organs, including in the brain parenchyma. Thus, in this paper, we prepared PLGA Np surface modified with a BBB-penetrating peptide (similopioid peptide) for BBB crossing and with a sialic acid residue (SA) for the interaction with brain receptors. This double coverage could allow to obtain novel targeted Np with a prolonged residence within the brain parenchyma, thus letting to reach a long-lasting brain delivery of drugs. The central analgesic activity of Loperamide (opioid drug, unable to cross the BBB) loaded in these novel Np was evaluated in order to point out the capability of the Np to reach and to remain in the brain. The results showed that the pharmacological effect induced by loaded Np administration remained significant over 24 h. Using confocal and fluorescent microscopies, the novel Np were localized within the tissue parenchyma (brain, kidney, liver, spleen and lung). Finally, the biodistribution studies showed a localization of the 6% of the injected dose into the CNS over a prolonged time (24 h). Notwithstanding an increased accumulation of SA-covered Np in those organs showing SA-receptors (liver, kidney, and lung), the pharmacological and biodistribution results are proofs of the ability of double targeted Np to enter the brain allowing the drug to be released over a prolonged time.

2010 - The role of fetal autopsy and placental examination in the causes of fetal death: a retrospective study of 132 cases of stillbirths. [Articolo su rivista]
Bonetti, L. R.; P., Ferrari; N., Trani; L., Maccio; S., Laura; S., Giuliana; Facchinetti, Fabio; Rivasi, Francesco
abstract

PURPOSE: To investigate the most plausible cause of stillbirth by evaluating clinical records and postmortem examination findings including placental analysis. METHODS: A retrospective cohort study concerning 132 stillbirths from 124 pregnancies occurred in the Mother-Infant Department of the University Hospital of Modena, Italy, from January 2000 to December 2004. Collected data were reviewed and classified according to the Gardosi ReCoDe system. RESULTS: A reasonable cause of fetal death was identified in 99/124 pregnancies (79.84\%). No associated relevant factors were disclosed in 25 fetuses (20.16\%) classified as unexplained stillbirths. A succeeding scrupulous analysis of the placenta and an accurate clinical record review were useful to detect other conditions in 82 cases, including 5 cases of unexplained stillbirth. The major relevant conditions associated to stillbirths were feto-placental infection especially in the early fetal gestation age, under the 24th week of gestation, and placental insufficiency occurred both in early and late gestation age fetuses and mainly associated with a IUGR (<10th customized percentile). The main frequent secondary conditions were represented by placental anomalies including cluster of avascular villi with stromal fibrosis associated to thrombosis in minor and/or major vessel(s). Through the further analysis of the placenta, we were able to reduce the unexplained stillbirth rate from 20.16 to 15\%. CONCLUSION: Accurate fetal autopsy and placental examination related to meticulous clinical collecting data are requisites in the valuation of stillbirth and could play an important role in reduction of unexplained stillbirth rate.

2009 - Cataract development in a young patient with lathosterolosis: A clinicopathologic case report [Articolo su rivista]
Cavallini, Gm; Masini, C; Chiesi, C; Campi, L; Rivasi, Francesco; Ferrari, P.
abstract

PURPOSE: To report a unique case of cataract in a young patient with lathosterolosis, a singular defect of cholesterol biosynthesis, and to report the clinical results and histopathologic findings after cataract surgery. METHODS: A 7-year-old patient with lathosterolosis, a rare defect of cholesterol biosynthesis, presented with a complex phenotype, including severe mental retardation, liver disease, multiple congenital anomalies, and bilateral posterior subcapsular cataracts. After a severe metabolic decompensation, a worsening in the lens opacity of the left eye occurred. The authors thus performed cataract surgery and made a histopathologic analysis of aspirated lenticular samples. The following examinations were performed at 1 day, 1 week, 3 months, 6 months, 12 months, and 24 months: refraction, biomicroscopy, and fundus evaluation. Visual acuity was not assessable due to lack of patient collaboration. The postoperative follow-up period was 24 months. RESULTS: Histopathologic findings on lenticular fragments revealed the presence of fibers disposed in a honeycomb, samples with homogeneous eosinophilic lens fibers, and other fragments characterized by bulgy elements referable to cortical fibers with degenerative characteristics. After surgery, biomicroscopic evaluation revealed no significant inflammation and good intraocular lens centration at the various control visits. No intraoperative or postoperative complications occurred. No posterior capsule opacification occurred 2 years after surgery. CONCLUSIONS: Lathosterolosis may lead to dysmetabolic cataract development; this unique case of cataract in such a patient has been successfully managed with surgery. Clinical results were excellent, and no complications occurred either intra- or postoperatively.

2009 - Dirofilarial human cases in the Old World, attributed to Dirofilaria immitis: a critical analysis. [Articolo su rivista]
Pampiglione, S; Rivasi, Francesco; Gustinelli, A.
abstract

AIMS: To review 28 cases of human dirofilariasis reported in the last 30 years in the Old World and attributed, by their respective authors, to Dirofilaria immitis or a species of Dirofilaria other than D. repens. METHODS AND RESULTS: Each case was analysed by examining the published accounts or by discussions with the authors, who were interviewed whenever possible. CONCLUSIONS: On the basis of these analyses we conclude that there is as yet no proof demonstrating with certainty that Old World D. immitis plays a pathogenic role in humans. It remains to be explained why D. immitis causes pulmonary infections in humans in the Americas while, in the Old World, this location appears, instead, to be always associated with D.repens, even though the former species is at times more frequent than the latter both in dogs and in the vectors. To explain this apparently different pathogenic power, two hypotheses are proposed: (i) there are perhaps twin populations with different genotypes on the two sides of the Atlantic, with different infective capacity for man and dog; (ii) the infective capacity to humans of the parasite could be modified, only in the Old World, by some unidentified factor, possibly inherent to the vector, that affects the complex mechanism of the vector-parasite relationship, affecting the survival of the larvae.

2009 - Distribution of second primari malignancies suggest a bidirectional effect between breast and endometrial cancer. A population-based study [Articolo su rivista]
Cortesi, L.; DE MATTEIS, Elisabetta; Rashid, I.; Cirilli, C.; Proietto, Manuela; Rivasi, Francesco; Federico, Massimo
abstract

INTRODUCTION: The aim of this study was to investigate the incidence of second primary tumors in patients with breast cancer (BC), with particular regard to bidirectional risk for endometrial cancer (EC). METHODS: A total of 7512 and 343 patients with first and second primary BC, respectively, were referenced to the expected number of cases calculated using the standardized incidence ratio (SIR) over the same period, to evaluate the observed and expected ratio between the groups. Data on tamoxifen use were also considered. RESULTS: A total of 499 women with primary BC developed a second tumor. The total SIR, that is, the ratio between observed second primary cancer among patients with BC and the expected primary cancers in the general population, was significantly higher (SIR = 1.23; 95% confidence interval, 1.12-1.34; P = 0.007), particularly for melanoma (2.25), EC (2.15), ovarian cancer (1.74), hematologic malignancies (1.36), and bilateral BC (1.25). A greater risk of BC after thyroid (2.22) and EC (1.62) was also observed. Furthermore, the risk of developing EC was higher in patients treated with tamoxifen (SIR = 2.50 vs 1.34). CONCLUSIONS: Bidirectional risk of endometrial cancer was not exclusively related to tamoxifen use.

2009 - Engineered polylactide-co-glycolide(PLGA) Np as drug delivery systems for the Central Nervous System [Relazione in Atti di Convegno]
Tosi, Giovanni; Costantino, Luca; Rivasi, Francesco; Bondioli, Lucia; Ruozi, Barbara; Vergoni, Anna Valeria; Tacchi, Raffaella; Bertolini, Alfio; Vandelli, Maria Angela; Forni, Flavio
abstract

Nanoparticulate polymeric systems (nanoparticles, Np) have been widely studied for the delivery of drugs to a specific target site. Np have been recently considered for the therapy of various brain diseases. The major problem in accessing the central nervous system (CNS) is due to the presence of the Blood-Brain Barrier (BBB). Recently, it has been shown the possibility to reach the CNS district crossing the BBB using nanoparticles (Np) made of polylactide-co-glycolide (PLGA), modified with a simil-opioid sequence and different glycosidic moieties. Firstly, PLGA was modified with different glycol-heptapetides (Glucose, Lactose, Xylose, and Mannose as sugar moieties and with a single [P] or a triple sequence of heptapeptides [3P]). Then, after i.v. administration, Np, labeled with covalent linkage with a fluorescent dye, were demonstrated to be able to cross the BBB by using confocal microscopy. A strong analgesic effects due to the encapsulated Loperamide, a P-glycoprotein (P-gp) substrate model drug, demonstrated the ability of modified PLGA Np to cross the BBB, after i.v. administration. The effect was different in the intensity and in the time period according to the different surface modification, being the Glucose preferable when compared with the other ones. When 3P-PLGA Np were used, a different profile in the pharmacological activity was assessed, i.e. a sudden maximum analgesic effect followed by a fast decrease over the time. Finally, the biodistribution of Np loaded with Rhodamine-123 (P-gp substrate) was analyzed quantifying the fluorescent intensity in the different organs including brain, in order to better understand the fate of these modified Np.

2009 - Enterobiasis in ectopic locations mimicking tumor-like lesions. [Articolo su rivista]
Pampiglione, S; Rivasi, Francesco
abstract

Both the clinical and the histopathological diagnostic difficulties of oxyuriasis in unusual sites and their importance from a clinical point of view are pointed out. The authors report two ectoptic cases of enterobiasis observed in Northern Italy, one located in a fallopian tube of a 57-year-old woman and the other in a perianal subcutaneous tissue of a 59-year-old man, mimicking tumor-like lesions. The authors take advantage of the occasion to focus the attention of the medical world on this subject, lamenting the scarce importance given to this parasitosis in university courses of medical schools and in medical textbooks as it is incorrectly considered “out-of-fashion.”

2009 - Expression of estrogen receptor in hemangioma of the uterine cervix: Reports of three cases and review of the literature [Articolo su rivista]
Reggiani Bonetti, Luca; Boselli, F.; Lupi, M.; Bettelli, S.; Schirosi, L.; Bigiani, N.; Sartori, G.; Rivasi, Francesco
abstract

The occurrence of hemangioma in the female genital tract, particularly in uterine cervix, is rare. The majority of them show asymptomatic behavior. Surgical excision remains curative in most of the cases. Conservative therapies such as sclerosing agents, cryotherapy, and CO(2) laser excision may be alternatively applied. We present three cases of hemangiomas of the cervix in asymptomatic women, diagnosed as cavernous hemangioma in two cases and capillary hemangioma in one. All tumors were immunoreactive for CD31, CD34, factor-VIII-related antigen. Focal expression of estrogen receptors was detected. No positivity was obtained with progesterone receptor antibodies. The presence of estrogen receptor in the endothelial cells of the hemangioma of the cervix suggests a direct role of this hormone in the hemangioma development. A possible target therapy is discussed.

2009 - External ophthalmomyiasis by Oestrus ovis larvae diagnosed in a Papanicolaou-stained conjunctival smear. [Articolo su rivista]
Rivasi, Francesco; Campi, L; Cavallini, Gm; Pampiglione, S.
abstract

Human ophthalmomyiasis is an eye infection associated with the larvae of certain flies of the Order Diptera (Insecta). This parasitic infection is classified as internal, orbital or external in relation to the location of the larvae.1 External ophthalmomyiasis is caused by species of a number of families, which include Oestrus ovis. This species, also called 'sheep bot fly', is a parasite specific to ovines and can only incidentally affect man. Adult Oestrus ovis females normally project their larvae into the muzzle of sheep while flying. In humans, the face and particularly the eyes are affected, these larvae being responsible for most cases of human external ophthalmomyiasis.2,3 In sheep, the larvae climb into the nasal passages reaching the frontal sinuses. After a few months, they detach and complete their life cycle in the soil from which the adult emerges at the next favourable season. The cycle ends in the human host as the parasite dies after a few days or weeks. While the infection is uncommon and reported only sporadically in Northern Italy, shepherds, farmers and people living in rural areas where sheep are bred are particularly affected.4,5 The larva, a millimetre in length and equipped with two oral hooks and numerous rows of tiny spines, irritates the conjunctival layer provoking an acute foreign body sensation, photophobia, blepharospasm, a watery to mucopurulent discharge, a sometimes painful chemosis with oedema of the eyelids.2,4 The prognosis is normally benign. Careful conjunctival examination can demonstrate the typical larvae. We report a human case of this infection, which occurred in Northern Italy and was diagnosed by cytological examination of a Papanicolaou-stained conjunctival smear.

2009 - Glycopeptide-decorated nanoparticles as drug carriers for CNS: effects of surface coverage and carbohydrate type [Articolo su rivista]
Tosi, Giovanni; Costantino, Luca; Rivasi, Francesco; Ruozi, Barbara; Bondioli, Lucia; Vergoni, Anna Valeria; Tacchi, Raffaella; Bertolini, Alfio; Vandelli, Maria Angela; Forni, Flavio
abstract

n order to study the ability of peptide-decorated PLGA Np to act as CNS drug delivery agents, the effect of various degrees of Np surface coverage by the peptide H2N-Gly-L-Phe-D-Thr-Gly-L-Phe-L-Leu-L-Ser(O-R)-CONH2 (R = -D-glucose) and of the type of carbohydrate present on Ser (R= H, -D-glucose, -D-xylose, -D-lactose, -D-Mannose) were evaluated. Loperamide was used as a model drug and its presence on rat CNS was evaluated by means of its pharmacological effect (antinociceptive assay, hot-plate test). The pharmacological effect exerted by loperamide loaded into Np demonstrated to be strongly dependent on the degree of peptidic surface coverage of Np. Thus, in the presence of a high surface coverage, a very short effect is observed, which appears early on (0.5 min) after Np iv administration. Moreover, the sugar moiety influences markedly the CNS effect of loperamide loaded into the peptide-decorated Np: among the carbohydrates here examined, the presence of Beta-D-glucose on the Ser of the peptide showed the best results, both in terms of the maximum effect and length.

2009 - Mature Solid Teratoma of the Fallopian Tube Mimicking Metastasis of Endometrial Adenocarcinoma: A Case Report. [Articolo su rivista]
Roncati, L; Barbolini, G; Ghirardini, G; Rivasi, Francesco
abstract

We report a mature solid teratoma of the fallopian tube in an elderly woman. This mass was noted on CT scan and considered metastatic in nature since following a bioptical diagnosis of endometrial adenocarcinoma. Hysterectomy and bilateral salpingectomy and ovariectomy were performed and a second minor mature solid teratoma was discovered inside the right ovary. Neoplasms of the fallopian tube are very uncommon and this is the first Italian case to be added to about other 60 of the literature. Moreover it joins minimum teratomatous diameter with maximum recorded age.

2009 - Unexpected intrauterine fetal death in parvovirus B19 fetal infection [Articolo su rivista]
Silingardi, Enrico; Santunione, Anna Laura; Rivasi, Francesco; Gasser, B; Zago, S; Garagnani, Lorella
abstract

The AA. presents 5 cases of maternal-fetal infection from parvovirus B19. The aspects anatomopathologic, diagnostic, clinical and professional liability are discussed

2008 - Alveolar rhabdomyosarcoma of the uterine cervix. A case report confirmed by FKHR break-apart rearrangement using a fluorescence in situ hybridization probe on paraffin-embedded tissues. [Articolo su rivista]
Rivasi, Francesco; Botticelli, L; Bettelli, Sr; Masellis, G.
abstract

Alveolar rhabdomyosarcoma (ARMS) is a very rare malignant soft tissue tumor found in the uterine cervix. In fact, to our knowledge, only 3 cases have previously been described in the literature. A 49-year-old premenopausal woman who had a history of vaginal bleeding underwent hysterectomy for multiple uterine nodules. Pathologic examination showed multiple leiomyomas in the uterus and ARMS in the cervix. An FKHR break-apart rearrangement by fluorescence in situ hybridization (FISH) probe on paraffin-embedded tissues identified specific chromosomal abnormalities. Systemic chemotherapy and pelvic irradiation were also performed. She remains in clinical remission from neoplastic recurrences 14 months after surgery. The literature has been reviewed; the histologic differential diagnosis of this rare lesion has been discussed and FISH has been suggested to be useful in differentiating ARMS from other poorly differentiated round cell tumors.

2008 - FISH analysis in cell touch preparations and cytological specimens from formalin-fixed fetal autopsies. [Articolo su rivista]
Rivasi, Francesco; Schirosi, L; Bettelli, S; Bigiani, N; Curatola, C.
abstract

Postmortem studies on still-borns and miscarriages are important to define the sex and eventually the morphologic anomalies correlated to chromosomal aberrations. When the conditions for carrying out a cytogenetic study do not exist, these chromosomal alterations can be investigated by nucleic acid fluorescent in situ hybridization (FISH), which can be performed on interphase nuclei, usually on formalin-fixed paraffin embedded tissues or on fresh cytological specimens. The objective of the present study is to prove whether this technique can be successfully applied to formalin-fixed cell touch preparations and cytological specimens obtained from foetal autopsies. The study was carried out 12 abortions some of which were spontaneous and some of which were therapeutic. The materials were formalin-fixed. Cell touch preparations and cytological specimens were obtained. The FISH was performed using X/Y probes (Vysis) and the Aneuvysion Kit (05J38-030, Vysis), the probes being for chromosomes 13/21 and X/Y/18. To verify the reliability of the technique, the same reactions were also performed on fresh analogous materials. The slides were evaluable, and the probes hybridized to interphase nuclei showed distinct signals. All the samples were adequate for FISH analysis without any notable difference in the results. Moreover, it is technically possible to perform this analysis not only on fresh but particularly on formalin-fixed cytological specimens. On the other hand, the use of this type of cytological samples, as compared to formalin-fixed and paraffin embedded tissue sections, has the advantage of presenting intact, noncut nuclei with preserved cytomorphology, avoiding the problems of overlapping nuclei and making the identification of the real chromosomal arrangement easier.

2008 - Mosquito-based survey for the detection of flaviviruses and filarial nematodes in Aedes albopictus and other anthropophilic mosquitoes collected in northern Italy. [Articolo su rivista]
Masetti, A; Rivasi, Francesco; Bellini, R.
abstract

In order to optimize resources, an assay allowing the detection of several etiological agents would be useful. This paper describes a polymerase chain reaction (PCR)-based assay for the parallel detection of different pathogens in mosquitoes (Diptera: Culicidae). The assay combines the analysis of both RNA and DNA, hence allowing the detection of both flaviviruses (Flaviviridae: Flavivirus) and filarial nematodes (Spirurida: Onchocercidae). The sensitivity of diagnostic assay for both flavivirus and nematode infections was tested by means of spiked samples and resulted adequate for the purpose of screening mosquito samples. The assay was implemented to check pathogen infections in 637 mosquitoes field-collected in Romagna, northern Italy. The integrity of RNA extracted from mosquito pools was checked by control amplifications targeting the 18 S rRNA of mosquitoes. Control amplifications were successful in 118 out of 119 pools. Flavivirus RNA was not found in any of these 118 pools, whereas DNA of Dirofilaria immitis (Leidy) was detected in one pool of Aedes albopictus (Skuse).

2008 - Periorbital subcutaneous tumor-like lesion due to Dirofilaria repens [Articolo su rivista]
Eccher, A; Dalfior, D; Gobbo, S; Martignoni, G; Brunelli, M; Decaminada, W; Bonetti, F; Rivasi, Francesco; Barbareschi, M; Menestrina, F.
abstract

Dirofilariasis is a zoonotic infection, which is occasionally seen in humans and rarely found as a subcutaneous orbital swelling. The authors report a case of a 62-year-old woman presented with a 3-month history of a right periorbital subcutaneous nodule. Treatment with antibiotics and corticosteroids was not satisfactory. Magnetic resonance imaging analysis showed a nodule with a central colliquative area. The lesion displaced the eyeball superiorly but did not affect the intraorbital muscles. The patient was subjected to excisional biopsy and the nodule measured 15 mm. Histological findings showed microabscess reaction with heterogeneous lymphoid infiltration. Additional consecutive sections finally showed Dirofilaria repens, curled up in spirals with external cuticular ridges in an environment characterized by epithelioid cells. The lesion did not recur for 5 months. Periorbital swelling can be rarely caused by Dirofilaria repens; therefore, this diagnosis should be considered in all cases of subcutaneous inflammatory or tumor-like lesion of unknown etiology.

2008 - P16 ink4a and HPV L1 immunohistochemistry is helpful for estimating the behavior of low-grade dysplastic lesions of the cervix uteri [Articolo su rivista]
Negri, G; Bellisano, G; Zannoni, Gf; Rivasi, Francesco; Kasal, A; Vittadello, F; Antoniazzi, S; Faa, G; Ambu, R; EGARTER VIGL, E.
abstract

As only a minority of low-grade dysplastic lesions of the cervix uteri will eventually progress to carcinoma, predicting the behavior of these lesions could be of high value in clinical practice. The aim of the study was to evaluate p16 ink4a and L1 as immunohistochemical markers of the biologic potentiality of low-grade dysplasia of the uterine cervix. The study included 38 conization specimens with coexisting cervical intraepithelial neoplasia grade 1 (CIN1) and 3 (CIN3) (group A) and 28 punch biopsies from women with CIN1 and proven spontaneous regression in the follow-up (group B). In group A, all CIN3 were p16 ink4a positive (p16+) and L1 negative (L1-). The CIN1 of this group were p16+L1- and p16+L1+ in 68.42% and 31.57%, respectively. No other expression pattern was found in this group. In group B, the p16+L1-, p16+L1+, p16-L1+, and p16-L1- patterns were found in 3.57%, 25%, 14.29%, and 57.14%, respectively. Overall, 96.29% p16+L1- CIN1 were found in group A, whereas all the p16-L1+ and p16-L1- CIN1 were found in group B. A significant difference between staining pattern distributions of group A and B was observed (P&lt;0.0001). The results of the study show that p16 ink4a and L1 immunohistochemistry can be helpful for estimating the biologic potentiality of low-grade squamous cervical lesions. Particularly in cases in which the grade of the lesion is morphologically difficult to assess, the p16/L1 expression pattern could be useful for planning the clinical management of these women.

2008 - Spontaneous umbilical cord hematoma: An unusual cause of fetal mortality: A report of 3 cases and review of the literature [Articolo su rivista]
Gualandri, G; Rivasi, Francesco; Santunione, Anna Laura; Silingardi, Enrico
abstract

Spontaneous hematoma of the umbilical cord represents a rare cause of fetal morbidity and mortality and the outcome is poor in half of the cases. There are many risk factors, such as infections, morphologic anomalies, alterations of the vessel walls, prolapses, twisting and traction of the cord, but in many cases the causes remain unknown. We present 3 cases of umbilical cord hematoma which took place at the end of the pregnancy and were followed by perinatal death of the fetus. In the 3 cases, which were autopsied including macroscopical and histopathologic examination of the placenta and the umbilical cord, a cordonal pathology was present; in all cases, there were alterations of the vascular wall, and in the third case inflammatory vasculopathy was found. In all 3 cases, the cause of death was attributed to acute anoxia due to the cordonal hematoma.

2008 - 3-T MRI in the preoperative evaluation of depth of myometrial infiltration in endometrial cancer. [Articolo su rivista]
Torricelli, Pietro; Ferraresi, S; Fiocchi, F; Ligabue, Guido; Jasonni, Vm; DI MONTE, I; Rivasi, Francesco
abstract

The objective of our study was to evaluate the diagnostic accuracy of 3-T MRI in determining the depth of myometrial infiltration in patients with endometrial cancer.Fifty-two patients (43 postmenopausal) with histopathologically proven endometrial carcinoma underwent preoperative 3-T MRI. The following sequences were performed: axial T1 fast spin-echo (FSE); axial, parasagittal, and paracoronal T2 FSE; paracoronal 3D T1 inversion recovery gradient-echo after contrast administration; and parasagittal fat-suppressed T1 FSE. All patients underwent a hysterectomy. The MRI findings were compared with histopathology results. The quantity and degree of artifacts were evaluated.. MRI performed on a 3-T unit was in agreement with histopathology in assessing the depth of invasion in 86.4\% (44/52) of the patients with a mean sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of 83.5\%, 93.9\%, 77.8\%, 92.2\%, and 89.7\%, respectively. Performance values were also assessed for single stages of myometrial infiltration. For the detection of an intramucosal lesion (MRI, 12/52; histopathology, 6/52), sensitivity was 100\%; specificity, 86.9\%; PPV, 50\%; NPV, 100\%; and accuracy, 88.5\%. For the detection of myometrial infiltration that was less than 50\% (MRI, 12/52; histopathology, 16/52), sensitivity was 62.5\%; specificity, 94.4\%; PPV, 83.3\%; NPV, 85\%; and accuracy, 84.6\%. For the detection of myometrial infiltration that was greater than 50\% (MRI, 28/52; histopathology, 30/52), sensitivity was 93.3\%; specificity, 100\%; PPV, 100\%; NPV, 91.7\%; and accuracy, 96.2\%. The following artifacts were found: abdominal wall movement, nine patients (not affecting image quality); peristalsis, 16 patients (two deeply affecting, one affecting, and 13 scarcely affecting); magnetic susceptibility artifact, four patients (not affecting); chemical shift, 20 patients (four scarcely affecting and 16 not affecting); and dielectric effect, six patients (four deeply affecting and two affecting).In evaluating the depth of myometrial infiltration in patients with endometrial cancer, 3-T MRI showed high diagnostic accuracy-equivalent to that of 1.5-T MRI reported in the literature. Artifacts did not significantly affect image quality.

2007 - Clinical phenotype of lathosterolosis [Articolo su rivista]
Rossi, M; D'Armiento, M; Parisi, I; Ferrari, Paola; Hall, Cm; Cervasio, M; Rivasi, Francesco; Balli, Fiorella; Vecchione, R; Corso, G; Andria, G; Parenti, G.
abstract

Lathosterolosis (LS) is a defect of cholesterol biosynthesis due to the deficiency of the enzyme sterol-C5-desaturase. Only two patients have been described to date, both presenting with multiple malformations, mental retardation, and liver involvement. In addition in one of them pathological examination revealed mucolipidosis-like inclusions on optic microscopy analysis, and peculiar lysosomal lamellar bodies on electron microscopy analysis. This study is focused on a better characterization of the clinical phenotype of LS. We describe a further case in a fetus, sibling of the first patient reported, presenting with neural tube defect, craniofacial and limb anomalies, and prenatal liver involvement. The fetal phenotype suggests the possible occurrence of significant intrafamilial variability in LS, and expands the phenotypic spectrum of the disease. Histological examination of autopsy samples from the fetus and skin fibroblasts from the living sibling suggested that the mucolipidosis-like picture previously reported is not a constant feature of LS, being possibly associated with the most severe biochemical defects, but confirmed the ultrastructural finding of lamellar inclusions. The LS phenotype appears to be characterized by the distinctive association of a recognizable pattern of congenital anomalies, involving axial and appendicular skeleton, liver, central nervous and urogenital systems, and lysosomal storage. This condition partially overlaps with other defects of sterol metabolism, suggesting intriguing pathogenic links among these conditions.

2007 - Detection of Mycobacterium tuberculosis DNA by polymerase chain reaction from paraffin samples of chronic granulomatous endometritis. [Articolo su rivista]
Rivasi, Francesco; Curatolo, C; Garagnani, L; Negri, G.
abstract

The histological diagnosis of tuberculosis endometritis is often troublesome. Indeed, the typical histological features are often absent and the sensitivity of the Ziehl–Neelsen stain for acid-fast bacilli is very low, about 2–3%.1,2 On the other hand, since the clinical diagnosis of tuberculosis may also be difficult, clinicians often have to rely on histology. A dramatic improvement in sensitivity and specificity of the diagnosis of mycobacterial diseases has been achieved in recent years with the development of molecular techniques.3–5 We explored the feasibility of detection of Mycobacterium tuberculosis DNA by polymerase chain reaction (PCR) in paraffin-embedded tissues of the endometrium and compared the results with the previous morphological diagnosis.

2007 - Modified PLGA Nanoparticles as drug carriers for CNS delivery [Relazione in Atti di Convegno]
Tosi, Giovanni; Costantino, Luca; Bondioli, Lucia; Ruozi, Barbara; Leo, Eliana Grazia; Rivasi, Francesco; Vergoni, Anna Valeria; Bertolini, Alfio; Tacchi, Raffaella; Forni, Flavio; Vandelli, Maria Angela
abstract

Modified PLGA Nanoparticles as drug carriers for CNS delivery

2007 - Nanoparticelle polimeriche per il direzionamento di farmaci al Sistema Nervoso Centrale [Relazione in Atti di Convegno]
Tosi, Giovanni; Costantino, Luca; Ruozi, Barbara; Bondioli, Lucia; Rivasi, Francesco; Vergoni, Anna Valeria; Bertolini, Alfio; Forni, Flavio; Vandelli, Maria Angela
abstract

Nanoparticelle polimeriche per il direzionamento di farmaci al Sistema Nervoso Centrale

2007 - Nanoparticles and Brain Targeting [Relazione in Atti di Convegno]
Tosi, Giovanni; Ruozi, Barbara; Costantino, Luca; Rivasi, Francesco; Leo, Eliana Grazia; Bertolini, Alfio; Vergoni, Anna Valeria; Forni, Flavio; Vandelli, Maria Angela
abstract

Nanoparticles and Brain Targeting

2007 - Ovary Cystadenofibroma Associated with Didelphys Uterus in a Teenager: Conservative Laparoscopic Management [Articolo su rivista]
A., Tirelli; Rivasi, Francesco; Volpe, Annibale; S., Ferrari; Cagnacci, Angelo
abstract

Serous cystadenofibromas are rare, nonmalignant tumors that develop inpostmenopausal women, with an incidence of 4.5%. Only a few cases of ovariancystadenofibroma in young patients have been reported in the literature. Althoughthis type of tumor has a rare, malignant potential, it may appear bothmacroscopically and ultrasonographically as malignant. It is well advised to beaware of the possibility of a cystadenofibroma before selecting an aggressivesurgical approach in young patients. In this paper, we report on a rare case of a 15-year-old female who was affected by a benign serous cystadenofibroma associatedwith a didelphys uterus, and who was treated with a conservative laparoscopicovarian resection. (J GYNECOL SURG 23:73)

2007 - Peptide-derivatized nanoparticles as carriers of drugs into the central nervous system [Relazione in Atti di Convegno]
Tacchi, Raffaella; Vergoni, Anna Valeria; Tosi, Giovanni; Costantino, Luca; Rivasi, Francesco; Bertolini, Alfio; Ruozi, Barbara; Forni, Flavio; Vandelli, Maria Angela
abstract

Peptide-derivatized nanoparticles as carriers of drugs into the central nervous system

2007 - Targeting the Central Nervous System: in vivo experiments with peptide-derivatized nanoparticles loaded with Loperamide and Rhodamine-123 [Articolo su rivista]
Tosi, Giovanni; Costantino, Luca; Rivasi, Francesco; Ruozi, Barbara; Leo, Eliana Grazia; Vergoni, Anna Valeria; Tacchi, Raffaella; Bertolini, Alfio; Vandelli, Maria Angela; Forni, Flavio
abstract

Polymeric nanoparticles (Np) represent one of the most innovative non-invasive approaches for the drug delivery to the central nervous system (CNS). It is known that the ability of the Np to cross the Blood Brain Barrier (BBB), thus allowing the drugs to exert their pharmacological activity in the central nervous district, is linked to their surface characteristics. Recently it was shown that the biocompatible polyester poly(D,L-lactide-co-glycolide) (PLGA) derivatized with the peptide H2N-Gly-L-Phe-D-Thr-Gly-L-Phe-L-Leu-L-Ser(O--D-Glucose)-CONH2 [g7] was an useful starting material for the preparation of Np (g7-Np); moreover, fluorescent studies showed that these Np were able to cross the BBB. In this research, g-7 Np were loaded with Loperamide in order to assess their ability as drug carriers for CNS, and with Rhodamine-123, in order to qualitatively determine their biodistribution in different brain macro-areas. A pharmacological evidence is given that g7-Np are able to cross the BBB, ensuring, for the first time, a sustained release of the embedded drug, and that these Np are able to reach all the brain areas here examined. The ability to enter the CNS appears to be linked to the sequence of the peptidic moiety present on their surface.

2006 - Acute abdomen associated with schistosomiasis of the appendix [Articolo su rivista]
Gabbi, C.; Bertolotti, M.; Iori, R.; Rivasi, F.; Stanzani, C.; Maurantonio, M.; Carulli, N.
abstract

2006 - Appendicitis associated with presence of Schistosoma haematobium eggs: an unusual pathology for Europe - Report of three cases [Articolo su rivista]
Rivasi, Francesco; Pampiglione, S.
abstract

Three cases of appendicitis associated with presence of Schistosoma haematobium eggs in the appendix tissue are reported. The patients (two males and one female) were all from Ghana and had immigrated to Italy a few years previously. It is difficult to attribute the cause of the appendicitis to the parasite; it is more probable that the appendicular location of the eggs occurred accidentally many years earlier in an endemic zone of the country of origin, and that recently bacterial agents were able to provoke the present appendicitis. Since it is probable that with the increase in the number of immigrants to Europe from endemic countries (sub-Saharan Africa in particular) other similar cases may occur, it is important that the surgeon and the pathologist be aware of this pathology, which has so far been considered unusual.

2006 - Detection of Dirofilaria (Nochtiella) repens DNA by polymerase chain reaction in embedded paraffin tissues from two human pulmonary locations - Case report [Articolo su rivista]
Rivasi, Francesco; Boldorini, R; Criante, P; Leutner, M; Pampiglione, S.
abstract

We here report two new cases of human pulmonary dirofilariasis in men aged 62 and 64 from Northern and Central Italy, respectively. Both were asymptomatic and the infections were discovered incidentally when chest radiographs taken for another reason revealed the presence of a coin lesion. The initial clinical diagnosis was oriented towards a lung tumour, and an excisional lung biopsy after thoracotomy was necessary for the final diagnosis. Pathologically, the lesion consisted of a roundish subpleural infarct with a central thrombotic artery containing sections of an immature nematode: Dirofilaria repens was diagnosed histologically in one case, the necrotic condition of the worm allowing only genus identification, Dirofilaria, in the other case. In both samples, PCR analysis amplified a 246 bp product, specific for the IpS insert 11 of D. repens. The authors stress the role of PCR in the diagnosis of this parasite from paraffin samples, also in cases in which identification of the species was not possible by conventional morphology due to poor conservation of the worm. These cases represent the first PCR-based diagnosis of D. repens in a human pulmonary dirofilariasis on samples embedded in paraffin.

2006 - Examination of Cryptosporidium Parvum in human gastro-intestinal histological specimens by a confocal microscope [Abstract in Rivista]
Rivasi, Francesco; Tosi, Giovanni; P., Rossi; Ruozi, Barbara; E., Pozio
abstract

Examination of Cryptosporidium Parvum in human gastro-intestinal histological specimens by a confocal microscope

2006 - Histopathology of gastric and duodenal Strongyloides stercoralis locations in fifteen immunocompromised subjects [Articolo su rivista]
Rivasi, Francesco; Pampiglione, S; Boldorini, R; Cardinale, L.
abstract

Context.-Strongyloidiasis is a worldwide parasitic infection affecting approximately 75 million people. In Italy, it was more prevalent in the past among rural populations of irrigated areas. Objective.-To determine the histopathologic alterations of the gastric and duodenal mucosa associated with the presence of Strongyloides stercoralis parasites. Design.-Fifteen cases of strongyloidiasis were observed in immunocompromised patients during a recent 6-year period in Italy. S stercoralis was found histologically in gastric biopsies (10 cases), in a gastrectomy (1 case), and in duodenal biopsies (9 cases). In 5 cases the parasite was present both in gastric and duodenal biopsies. Four patients were affected by lymphoma, 2 by multiple myeloma, 2 by gastric carcinoma, 1 by chronic myeloid leukemia, 1 by sideroblastic anemia, 1 by colorectal adenocarcinoma, I by chronic idiopathic myelofibrosis, 1 by chronic gastritis, 1 by gastric ulcers, and 1 by rheumatoid arthritis in corticosteroid therapy. No patient was affected by human immunodeficiency virus infection. Strongyloidiasis was not clinically diagnosed. Results.-Histologic examination revealed several sections of S stercoralis larvae, many eggs, and some adult forms. All the parasites were located in the gastric and/or the duodenal crypts. Eosinophils infiltrating into the lamina propria were found in all cases; their intensity was correlated with the intensity of the infection. Conclusions.-Histologic diagnosis of strongyloidiasis must be taken into consideration when examining both gastric and duodenal biopsies in immunocompromised patients, to avoid the development of an overwhelming infection of the parasite, which is dangerous for the life of the patient.

2006 - Nanoparticelle con superficie modificata ad alta densità [Abstract in Atti di Convegno]
Tosi, Giovanni; Gandolfi, Francesca; Ruozi, Barbara; L., Bossy Nobs; R., Gurny; Rivasi, Francesco; Forni, Flavio; Vandelli, Maria Angela; Costantino, Luca
abstract

Nanoparticelle con superficie modificata ad alta densità

2006 - Nanoparticelle modificate per il drug targeting [Relazione in Atti di Convegno]
Tosi, Giovanni; Ruozi, Barbara; Costantino, Luca; Leo, Eliana Grazia; Rivasi, Francesco; M. A., Gomez; E., Pozio; Forni, Flavio; Vandelli, Maria Angela
abstract

Nanoparticelle modificate per il drug targeting

2006 - Nanoparticelle per il direzionamento cerebrale di farmaci [Articolo su rivista]
Tosi, Giovanni; Costantino, Luca; Gandolfi, Francesca; Ruozi, Barbara; Rivasi, Francesco; Vandelli, Maria Angela; Forni, Flavio
abstract

Polymeric nanoparticles (Np) represent one of the most innovative non-invasive approaches for the drug delivery to the central nervous system (CNS). It is known that the ability of the Np to cross the Blood Brain Barrier (BBB), thus allowing the drugs to exert their pharmacological activity in the central nervous district, is linked to their surface characteristics. Recently it was shown that the biocompatible polyester poly(D,L-lactide-co-glycolide) (PLGA) derivatized with the peptide H2N-Gly-L-Phe-D-Thr-Gly-L-Phe-L-Leu-L-Ser(O--D-Glucose)-CONH2 [g7] was an useful starting material for the preparation of Np (g7-Np); moreover, fluorescent studies showed that these Np were able to cross the BBB. In this research, g-7 Np were loaded with Loperamide in order to assess their ability as drug carriers for CNS, and with Rhodamine-123, in order to qualitatively determine their biodistribution in different brain macro-areas. A pharmacological evidence is given that g7-Np are able to cross the BBB, ensuring, for the first time, a sustained release of the embedded drug, and that these Np are able to reach all the brain areas here examined. The ability to enter the CNS appears to be linked to the sequence of the peptidic moiety present on their surface.

2006 - Nanoparticulate drug carriers based on hybrid poly(D,L-lactide-co-glycolide)-dendron structures [Articolo su rivista]
Costantino, Luca; Gandolfi, Francesca; L., BOSSY NOBS; Tosi, Giovanni; R., Gurny; Rivasi, Francesco; Vandelli, Maria Angela; Forni, Flavio
abstract

We describe a general method for incorporating target moieties in a well-defined arrangement into the surface of biocompatible polyester poly(D,L-lactic-co-glycolic acid) (PLGA) materials using dendrons. In this way it is possible to obtain nanoparticles (NPs) with a high degree of surface coverage. This new strategy was successfully applied to the preparation of peptide- and beta-D-glucose-covered NPs. The first application is based on the discovery of NPs made of conjugates between PLGA and short peptidic sequences able to cross the blood-brain barrier (BBB) after systemic administration. In this paper, we used a branched structure (dendron) in order to prepare a derivative of PLGA able to form, by simple nanoprecipitation, NPs with a higher degree of surface coverage than previously reported by us, characteristic that could influence the uptake by the liver and spleen. The NPs thus obtained retain the ability to cross the BBB and possess a core-shell structure, as evidenced from zeta-potential, X-ray photoelectron (ESCA) spectroscopy and elemental analyses. These results are comparable with the NPs obtained by the derivatization of preformed NPs. The same strategy, namely the use of a branched spacer (a dendron or a G1 dendrimer) inserted between one end of the PLGA chain and a derivatizing molecule, was also successfully applied to obtain beta-D-glucose-covered NPs; in this case, the surface analysis of the NPs was performed by using high resolution magic angle spinning (HRMAS) NMR spectroscopy and zeta-potential measurements.

2006 - Per partum death at term pregnancy due to spontaneous cord hematoma. [Articolo su rivista]
Gualandri, G; Rivasi, Francesco; Santunione, Anna Laura; Silingardi, E.
abstract

hematoma of the umbilical cord is rare but the outcome is poor in the half of the cases. spontaneous cord hematoma can present morphologically in a different manner so in all cases in which acute asphyxia is verified, it is necessary to proceed to an accurate study of the cord, in fact we feel that the diagnosis of spontaneous cord hematoma is understimated because a study wich multiple section in not performed routinely

2006 - Perinatal aspergillosis: a case with fatal outcome. [Articolo su rivista]
Rivasi, Francesco; Cesinaro, Am; Curatola, C; REGGIANI BONETTI, Luca
abstract

Aspergillosis is an uncommon perinatal infection diagnosed with increasing frequency in recent years. We report a premature infant who required both nutrition and ventilation artificially assisted and developed a disseminated invasive nosocomial infection from Aspergillus flavus. Autopsy revealed marked hypotrophy of the thymus and multisystem invasive aspergillosis chiefly involving the vascular and alimentary systems and also the respiratory tract, the central nervous system, and the skin. From what we know, this is the first case of the literature with a misleading initial clinical presentation involving the alimentary tract (hepatomegaly, ingravescent cholestatic icterus) and evolving in intestinal occlusion.

2006 - Sudden death from tubercular myocarditis [Articolo su rivista]
Silingardi, Enrico; Rivasi, Francesco; Santunione, Anna Laura; Garagnani, Lorella
abstract

Tuberculous myocarditis is a rare finding. We present the case of a 33-year-old woman who was in good health and who died suddenly at home. Autopsy and histopathologic examinations revealed granulamatous lesions in the myocardium, lungs, lymph nodes, liver, and spleen. No fast acid bacilli were demonstrated on histological examination. The presence of a Mycobacterium tuberculosis DNA complex was identified using a polymerase chain reaction (PCR) on formalin-fixed paraffin-embedded histological samples. An HIV test carried out on the blood obtained during the autopsy was negative according to the DNA amplification technique (PCR) and enzyme-linked immunosorbent assay serological test. We hypothesize that the mechanism of death was severe ventricular arrhythmia due to granulomatous proliferation in the structures of the interventricular septum.

2006 - Vegetable cells in Papanicolaou-stained cervical smears [Articolo su rivista]
Rivasi, Francesco; Tosi, Giovanni; Ruozi, Barbara; Curatola, Carlo
abstract

Vegetable cells are unusual findings in Papanicolaou-stained cervical smears; these structures could be wrongly mistaken for abnormal human cells, worm eggs, or spores by a cytologist encountering the possibility of meeting those elements in cytological analysis. Five cervicovaginal smears showing similar vegetable cells have been detected over a 3-yr period (2002-2004) in the course of a population screening program for cancer of the uterine cervix in Modena (Italy) involving 32,500 women. According to the clinical histories of the patients, the vaginal pharmaceutical drugs or appliances used were of different types: vaginal lavages, pessaries, and vaginal creams. Following a careful investigation, the only substance that can lead to vegetal elements has been identified as polysaccharide galactomannan, which is one of the excipient present in the drugs used. The authors have identified the origin of these contaminants and the means of pollution, using cytological and pharmaceutical investigation.

2005 - Anatomy of Tunga trimamillata Pampiglione et al., 2002 (Insecta, Siphonaptera, Tungidae) and developmental phases of the gravid female [Articolo su rivista]
Pampiglione, S; Fioravanti, Ml; Gustinelli, A; Onore, G; Rivasi, Francesco; Trentini, M.
abstract

This paper deals with some internal anatomical features observed in histological sections and freshly dissected mounts of Tunga trimamillata, a Siphonaptera recently discovered in Andean regions of Ecuador from several mammals, including man. It was possible to study in males and also non-gravid and gravid females, the location and anatomy of several organs not previously described for this species: the testes, epididymis, ganglia, Malpighian tubules, eyes, rectal ampulla with one of its pads and structures which could be interpreted as midgut diverticula, whose presence has not been recorded in the Siphonaptera. The process of neosomy in the female during pregnancy is illustrated by photographs of the consecutive developmental phases, taken at the stereomicroscope. Furthermore, Some details of the exoskeleton, spermatheca during different phases of pregnancy of the gravid female and the presence of a foreign body (parasite?) within the haemocoel have been displayed in specimens cleared with Hoyer's medium.

2005 - Characterization of liver involvement in defects of cholesterol biosynthesis: Long-term follow-up and review [Articolo su rivista]
Rossi, M; Vajro, P; Iorio, R; Battagliese, A; Brunetti Pierri, N; Corso, G; Di Rocco, M; Ferrari, P; Rivasi, Francesco; Vecchione, R; Andria, G; Parenti, G.
abstract

Inborn defects of cholesterol biosynthesis are a group of metabolic disorders presenting with mental retardation and multiple congenital anomalies (MCA/MR syndromes). Functional and structural liver involvement has been reported as a rare (2.5-6%) complication of the Smith-Lemli-Opitz syndrome (SLOS) and it has not been fully characterized. Here, we report on a long-term follow-up study of four patients with SLOS, and one case with lathosterolosis who presented with liver disease and underwent an extensive diagnostic work-up. Reports of liver involvement in cholesterol biosynthesis defects are reviewed. Two main different patterns of liver involvement emerged: progressive cholestasis, and stable isolated hypertransaminasemia. In our series, the first pattern was found in two patients with SLOS and one with lathosterolosis, and the second in two SLOS cases. Cholestasis was associated with early lethality and normal serum gamma-glutamyl-transferase (GGT) levels in SLOS, while possible prolonged survival and high GGT levels were seen in lathosterolosis. Hepatic fibrosis was present in both conditions. Liver biopsy performed in one of our SLOS patients with isolated hypertransaminasemia, showed only mild hydropic degeneration of the hepatocytes. The presence of liver involvement in 16% of the SLOS patients diagnosed at our Center suggests that this complication might have been underestimated in previously reported cases, possibly overshadowed by the severity of multiple malformations. Fetal hepatopathy, cholestasis, and isolated hypertransaminasemia can occur also in other disorders of cholesterol biosynthesis, such as mevalonic aciduria, desmosterolosis, Conradi-Hunermann syndrome, Greenberg dysplasia, and Pelger-Huet homozygosity syndrome. This group of inherited disorders should be considered in the differential diagnosis of patients presenting with liver disease associated with developmental delay and/or multiple malformations. Periodic liver function evaluations are recommended in these patients.

2005 - Conjugated poly(D,L-lactide-co-glycolide) for the preparation of in vivo detectable nanoparticles [Articolo su rivista]
Tosi, Giovanni; Rivasi, Francesco; F., Gandolfi; Costantino, Luca; Vandelli, Maria Angela; Forni, Flavio
abstract

Cellular localization of nanoparticles (Np) represents an important target in the understanding of their distribution after endovenous injection. The need of suitable devices and methodologies capable to detect Np in tissues or in cellular districts can be satisfied by Np which have to be easily recognizable by simple methods. Conjugations of poly(D,L-lactide-co-glycolide) with fluorescein and biotin allow fluorescent and immuno-histochemically active Np to be obtained. The fluorescein Np are detectable using fluorescent microscopy whereas biotin Np can be detected by optical microscopy after streptavidin-biotin-peroxidase complexation. In vivo experiments confirm the ability of these particles to be easily detected in the brain parenchyma or in the liver cell population according to the infusion pathway.

2005 - Entamoeba coli in strisci cervico-vaginali di pazienti portatrici di IUD a proposito di tre casi [Abstract in Atti di Convegno]
Rivasi, Francesco; P., Rossi; Tosi, Giovanni; E., Pozio
abstract

Entamoeba coli in strisci cervico-vaginali di pazienti portatrici di IUD a proposito di tre casi

2005 - Evidence for cycle-dependent expression of follicle-stimulating hormone receptor in human endometrium [Articolo su rivista]
LA MARCA, Antonio; Stabile, G; Rivasi, Francesco; Volpe, Annibale; Carducci Artenisio, A
abstract

Objective. It was the purpose of the present study to investigate whether human endometrium expresses follicle-stimulating hormone (FSH) receptor mRNA and peptide, and whether this expression is regulated in a cycle-dependent manner in endometrium derived from various phases of the menstrual cycle. Methods. FSH receptor mRNA and peptide expression were evaluated by reverse transcription-polymerase chain reaction and by immunohistochemistry in endometrium from 15 women undergoing hysteroscopy to evaluate the morphology of the uterine cavity or hysterectomy for leiomyomas. Results. FSH receptor mRNA was expressed by human endometrium, and its peptide was located immunohistochemically in both proliferative and secretory endometrial epithelial and stromal cells. A significant increase in immunoreactive FSH receptor was observed during the secretory phase. Conclusions. We have shown the presence of FSH receptor in human endometrium and demonstrated that FSH receptor immunostaining is upregulated in the secretory phase of the menstrual cycle. The dynamic pattern of receptor expression indicates that FSH may play a role in the regulation of endometrial function and possibly in the embryo-endometrium interaction.

2005 - MRI evaluation of myometrial invasion by endometrial carcinoma. Comparison between fast-spin-echo T2W and coronal FMPSPGR Gadolinium-dota-enhanced sequences [Articolo su rivista]
Nasi, F; Fiocchi, F; Pecchi, A; Rivasi, Francesco; Torricelli, Pietro
abstract

Purpose. The depth of myometrial invasion by endometrial carcinoma strongly affects the incidence of metastasis to regional nodes and influences the surgical strategies. The aim of this paper is to compare the results of FSE T2-w and Gadolinium-enhanced FMPSGR MR sequences in assessing the depth of myometrial invasion by endometrial cancer. Materials and methods. Forty-five women with histopathologically-proven endometrial carcinoma underwent preoperative MRI. Axial SE T1w, axial, sagittal and para-coronal FSE T2w and para-coronal Gadolinium-enhanced FMPSGR sequences were performed using a high field strength magnet (1.5T). Within one month of MR all patients underwent hysterectomy, and anatomical evaluation of the surgical specimen was done sectioning the uterus along the short axis. Based upon the results of the histological evaluation the results of the FSE T2w and Gadolinium-enhanced sequences were compared and the statistical difference between the results obtained was statistically evaluated. Results. The histological evaluation showed intramucosal neoplasm in 1 patients, myometrial infiltration less than 50% in 31 patients, myometrial infiltration more than 50% in 12 patients and transmural cancer in 1 patient. Statistical evaluation showed that the FSE T2w sequence had a global sensitivity and specificity of 80.6% and 87.6%, respectively, with a mean Negative Predictive Value of 92.6% and a mean Positive Predictive Value of 86%. Gadolinium-enhanced FMPSPGR sequence had a global sensitivity and specificity of 90.6% and 93.3%, respectively, with a mean Negative Predictive Value of 96,3% and a mean Positive Predictive Value of 88%. The staging accuracy (chi(2) test) on FMPSPGR images (95%) was higher than that on FSE T2w images (78%). Conclusions. In our experience Gadolinium-enhanced dynamic sequences increase the accuracy of MR imaging in diagnosing the depth of myometrial invasion. In particular they improve the visualisation of the inner myometrium, the so called subendometrial enhancing zone, whose disruption or changes are essential for diagnosing myometrial invasion. The major diagnostic advantages of the enhanced sequences were found in postmenopausal women, where visualisation of the junctional zone may be difficult in the T2w sequences. We believe that Gadolinium-enhanced dynamic sequences should be used whenever the diagnosis is unclear at FSE T2w sequences.

2005 - Nanoparticelle per il direzionamento cerebrale di farmaci [Relazione in Atti di Convegno]
Tosi, Giovanni; Costantino, Luca; Gandolfi, Francesca; Ruozi, Barbara; Rivasi, Francesco; Forni, Flavio; Vandelli, Maria Angela
abstract

Nanoparticelle per il direzionamento cerebrale di farmaci

2005 - Ovuli vaginali a rilascio prolungato come inquinanti in pap-test [Abstract in Atti di Convegno]
Tosi, Giovanni; Rivasi, Francesco; Ruozi, Barbara; Leo, Eliana Grazia; Vandelli, Maria Angela
abstract

Ovuli vaginali a rilascio prolungato come inquinanti in pap-test

2005 - Peptide-derivatized biodegradable nanoparticles able to cross the blood-brain barrier [Articolo su rivista]
Costantino, Luca; Gandolfi, Francesca; Tosi, Giovanni; Rivasi, Francesco; Vandelli, Maria Angela; Forni, Flavio
abstract

Injectable nanoparticulate drug carriers (Np) able to cross the blood-brain barrier (131313) have important potential applications for the treatment of diseases that affect the central nervous system (CNS). With the aim to create a system able to address Np to the CNS, we synthesized conjugates between a biodegradable copolymer, poly(D,L-lactide-co-glycolide) (PLGA), and five short peptides, by means of an amidic linkage. These peptides, that are similar to synthetic opioid peptides, were synthesized in turn by means of Fmoc solid-phase peptide synthesis. The new five modified copolymers thus obtained turned out to be valuable starting material for the preparation of Np; these were made fluorescent, in order to allow their localization after their administration, by inclusion of a fluorescent probe. The Np thus prepared were characterized (morphology, size and z-potential) and were shown to possess the peptidic moieties on their surface, as evidenced by ESCA spectroscopy. Then, their ability to cross the BBB was assessed by the in vivo Rat Brain Perfusion Technique and, in one case, by means of a systemic administration (rat femoral vein injection). Fluorescent and confocal microscopy studies showed that while PLGA Np are unable to cross the BBB, for the first time these solid Np surface-modified with peptides were shown to be able to cross the BBB.

2005 - Pyrexia, leukocytosis and elevated circulating platelets associated to uterine stromal sarcoma with rhabdoid differentiation [Articolo su rivista]
Jasonni, Valerio; LA MARCA, Antonio; G., Vito; M., Crotti; Rivasi, Francesco
abstract

Fever of unknown origin can be associated to soft tissues sarcoma and two cases are reported in the literature regarding sarcoma and pyrexia sustained by the tumor [1]. In the present report, we describe a case of uterine sarcoma associated to fever, leukocytosis and circulating elevated levels of platelets.A 46-year-old women with diagnosis of severe anemia (Hb 5.9 gr/dl) and uterine leiomyoma was admitted as an emergency to our hospital. The patient experienced normal cycles until 5 months before when cyclic menhorragia appeared.An office endometrial biopsy showed proliferative endometrium and the patient was submitted to progestins administration in order to reduce the cyclic bleeding. During the last 5 months, pyrexia of unknown origin appeared and the laboratory examination showed leukocytosis and increased platelets.On presentation, the physical exam was notable for an enlarged irregularly shaped uterus. There was no inguinal, axillary or supraclavicolar adenopathy.

2004 - Breast carcinoma metastases in paranasal sinuses, a rare occurrence mimicking a primary nasal malignancy. case report. [Articolo su rivista]
Marchioni, D; Monzani, Daniele; Rossi, G; Rivasi, Francesco; Presutti, Livio
abstract

Metastatic tumours to the paranasal sinuses are an exceedingly rare event, the large majority being of renal origin. Herein, a case of metastatic breast carcinoma to the right maxilla is described which occurred 4 years after radical mastectomy, clinically and radiologically presenting as a primary sinonasal mass. Only the histopathologic examination together with a broad spectrum of immunohistochemical antibodies were useful in confirming the origin of the neoplasm.

2004 - Infection with Cryptosporidium hominis and reinfection with Cryptosporidium parvum in a transplanted ileum [Articolo su rivista]
Pozio, E; Rivasi, Francesco; Caccio, Sm
abstract

A transplanted ileum was found to be infected with Cryptosporidium hominis 6 days after transplantation. Although the infection resolved, the ileum was later found to be infected with Cryptosporidium parvum. The presence of the parasite was not always correlated with diarrhea. No other gastrointestinal symptom was ever detected. Treatment with azithromycin and paromomycin apparently failed.

2004 - P16(INK4) stop expression and progression risk of low-grade intraepithelial neoplasia of the cervix uteri [Articolo su rivista]
Negri, G; Vittadello, F; Romano, F; Kasal, A; Rivasi, Francesco; Girlando, S; Mian, C; Egarter Vigl, E.
abstract

The aim of the study was to evaluate the immunohistochemical expression of p16(INK4a) as a marker of progression risk in low-grade dysplastic lesions of the cervix uteri. p16(INK4a) immunohistochemistry was performed on 32 CIN1 with proven spontaneous regression of the lesion in the follow-up ( group A), 31 ( group B) with progression to CIN3 and 33 ( group C) that were randomly chosen irrespective of the natural history of the lesion. p16(INK4a) staining pattern was scored as negative ( less than 5% cells in the lower third of dysplastic epithelium stained), as focally positive ( less than or equal to 25%) and as diffuse positive (> 25%). A diffuse staining pattern was detected in 43.8% of CIN1 of group A, 74.2% of group B and 56.3% of group C. No p16(INK4a) staining was detected in 31.3% and 12.9% CIN1 lesions of groups A and B, respectively. Overall, 71.4% and 37.8% of p16(INK4a)-negative and diffusely positive CIN1 had regressed at follow-up, whereas 28.6% and 62.2% negative and diffusely positive CIN1 were progressed to CIN3, respectively (P< 0.05). All CIN3 lesions analyzed during follow-up of group B were diffusely stained for p16(INK4a). Although p16(INK4a) may be expressed in low-grade squamous lesions that undergo spontaneous regression, in this study, CIN1 cases with diffuse p16(INK4a) staining had a significantly higher tendency to progress to a high-grade lesion than p16(INK4a)-negative cases. p16(INK4a) may have the potential to support the interpretation of low-grade dysplastic lesions of the cervix uteri.

2003 - Additional description of a new species of Tunga (Siphonaptera) from Ecuador [Articolo su rivista]
Pampiglione, S; Trentini, M; Fioravanti, Ml; Onore, G; Rivasi, Francesco
abstract

A new species of chigoe flea belonging to the genus Tunga jarocki, 1838 (Siphonaptera, Pulicidae, Tunginae), Tungo trimamillata, was recently described by Pampiglione et al. (2002). A better description and more details of the epidemiology of the flea are now presented. It is a species found in goats, pigs and cattle in Santa Isabel in Andean Ecuador. This new species differs from its most similar congener, Tunga penetrans (L., 1758), by several features, the most important of which are a) the presence on the anterior extremity of the gravid female of three rounded humps surrounding the head and thorax (which, however, are not visible if viewed in profile), b) slightly larger dimensions and C) the length of the first segment of the maxillary palpi which is longer than each of the other three.

2003 - Atypical lipomatous tumour (lipoma-like well-differentiated liposarcoma) arising in a pulmonary hamartoma and clinically presenting with pneumothorax [Articolo su rivista]
Rossi, Giorgio; Cavazza, A; Valli, R; Torricelli, Pietro; Richeldi, Luca; Rivasi, Francesco; Brambilla, E.
abstract

We document an uncommon variant of pulmonary hamartoma (PH), discovered in the left upper lobe of a 60-year-old man after an episode of pneumothorax, a unique clinical presentation for such an occurrence. The tumour showed a prominent leaf-like pattern and was mainly composed of mature fat with adipocytes of different size and scattered throughout lipoblasts and floret-like cells. A lobectomy was performed and more than 7 years after surgery the patient's course is still uneventful. This case represents an exceedingly rare example of an histologically malignant change in PH and bears a close clinicopathologic resemblance to atypical lipomatous tumours of soft tissues. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.

2003 - Early prenatal diagnosis of recurrent 46,XY partial gonadal dysgenesis. [Articolo su rivista]
V., Mazza; C., Ottolenghi; I. D., Monte; Baldassari, Francesco Vincenzo M.; Rivasi, Francesco; Volpe, Annibale; A., Forabosco
abstract

We present a case of early prenatal diagnosis of recurrent 46,XY partial gonadal dysgenesis, by combining early genetic and sonographic evaluations.The conceptus of a mother with a first child affected by 46,XY gonadal dysgenesis was sonographically evaluated at 21- and 23-mm BPD (12(+2) and 12(+6) LMP-based age) and the female genitalia were observed. Karyotype analyses was performed on amniotic fluid and it revealed a 46,XY complement without mosaicism. SRY was amplified by PCR for molecular analyses.We observed a discordance between female phenotype detected at 21 and 23 mm of biparietal diameter (12(+2) and 12(+6) LMP-based age) and male karyotype. In the child and the fetus, seminiferous cords were not recognisable, whereas rare Leydig cells and no germ cells could be identified. Internal and external genitalia were sexually ambiguous in the child and feminized in the fetus.This is the first case of early prenatal diagnosis of recurrent 46,XY partial gonadal dysgenesis and it points to the importance of combining early analyses of genetic sex with sonography in the management of anomalies of sexual development, with particular regard to syndromes for which the risk of recurrence is little understood.

2003 - Human sparganosis in Italy - Case report and review of the European cases [Articolo su rivista]
Pampiglione, S; Fioravanti, Ml; Rivasi, Francesco
abstract

Infections with Spargana, the larvae of Spirometra spp., are rarely found in humans in Europe. So far only six cases have been discussed in the literature, four from Italy and two from France. We here report a new case in a 50-year-old workman, a freshwater sports fisherman from Bologna in Northern Italy. The infection manifested as a subcutaneous nodule in the thigh, 2 X 3 cm in size, slightly painful when compressed, somewhat mobile under the skin, present for 9 months, with recurrent periods of local itchiness associated with redness and slight oedema. The lump was removed surgically Histological sections of the biopsied material revealed the presence of a sparganum. Drinking water contaminated by copepods, containing procercoid larvae of this parasite, seems to be the medium of infection.

2003 - On a new species of sand flea from Ecuador and tungiasis, a problem of Public Health in many developing countries]. [Articolo su rivista]
Pampiglione, S; Trentini, M; Fioravanti, Ml; Onore, G; Rivasi, Francesco
abstract

The authors recently described a new species of sand flea (genus Tunga) occurred in goat, sheep, cow, pig and man, in the Andean village of S.ta Isabel (Ecuador) and named Tunga trimamillata. Its most important morphological characteristics are: slightly larger dimensions than T. penetrans, both in male and female; presence on the anterior extremity of gravid female of three rounded humps surrounding head and thorax; length of the first segment of maxillary palpi which is longer than each of the other three. The importance of this parasite is due to the fact that it can cause the same damages as T. penetrans both in humans and domestic animals, with conseguent walking difficulties and local or generalized infections. For breeders, economic losses can be remarkable. Tungiasis is a serious problem of Public Health in many countries of Latin America and Subsaharian Africa, and it can be considered in these localities as an indicator of underdevelopment and poor hygiene conditions.

2002 - Atypical (bizarre) leiomyoma of the nasal cavity with prominent myxoid change [Articolo su rivista]
Vincenzi, A; Rossi, G; Monzani, Daniele; Longo, L; Rivasi, Francesco
abstract

A 72 year old woman presented complaining of nasal obstruction, rhinorrea, and epistaxis. At examination, a polypoid mass on the right posterior choana was revealed and subsequently removed. Light microscopic findings consisted of a diffuse proliferation of spindle shaped, pleomorphic cells with eosinophilic cytoplasm and blunt ended nuclei in a prominent myxoid background. The presence of numerous plurinucleate, bizarre cells made it very difficult to determine the malignant potential. Immunohistochemical evidence for leiomyogenic markers coupled with the low mitotic rate, the lack of an infiltrating growth pattern, and the indolent clinical course led to the diagnosis of atypical leiomyoma with prominent myxoid change. A literature survey confirmed that such a tumour is extremely rare at this site, but the biological behaviour seems to be similar to its uterine counterpart. Clinicians should be aware of this occurrence to prevent misdiagnosis because a conservative therapeutic approach is necessary in this disease.

2001 - Dirofilariasis due to Dirofilaria repens in Italy, an emergent zoonosis: report of 60 new cases [Articolo su rivista]
S., Pampiglione; Rivasi, Francesco; G., Angeli; R., Boldorini; Rm, Incensati; A., Maccioni; M., Pastomerlo; M., Pavesi; A., Ramponi; E., Valdes; M., Vetrugno
abstract

Aims: Sixty new cases of human dirofilariasis due to Dirofilaria repens, occurring in Italy between 1990 and 1999, are presented. This is the most extensive case study of this zoonosis reported worldwide by a single study group. The aim is to utilize this large experience to characterize the different histopathological findings in the parasitic lesions in man. Methods and results: Diagnosis was performed on histological sections of the nematode enclosed in the nodules excised at biopsy or surgery. The nematode was located in the subcutaneous tissue (49 cases), the epididymis (two cases), the spermatic cord (two cases), the lung (two cases), the breast (two cases), the omentum (two cases) and under the conjunctival tissue tone case). The majority of cases (46) were from Piedmont; the remainder were from Emilia-Romagna, Sardinia, Sicily, Tuscany, Apulia and Lombardy The histopathological features of the lesions are described and the clinical and epidemiological aspects of the zoonosis are discussed, The prevalence in Italy in general and in the area of Piedmont in particular comprising the provinces of Alessandria, Asti, Novara and Vercelli, which is one of the most severely affected areas of the world, is emphasized. The evident increase in the number of cases in the last few years is a clear indication that it is an emergent zoonosis. Conclusions: We recommend that each and every case observed be recorded, to enable the true extent of human dirofilariasis in Italy to be assessed, and that a reference centre be set up in the area to collate the data. The importance of the histopathologist's role in the diagnosis is stressed.

2001 - Gelatin microspheres crosslinked with D,L-glyceraldehyde as a potential drug delivery system: preparation, characterisation, in vitro and in vivo studies [Articolo su rivista]
Vandelli, Maria Angela; Rivasi, Francesco; Guerra, P.; Forni, Flavio; Arletti, R.
abstract

To overcome the restriction in using crosslinked gelatin in the pharmaceutical field, D,L-glyceraldehyde (GAL), a non-toxic crosslinking agent, was proposed. Gelatin microspheres crosslinked with different concentrations of GAL (0.5, 1 or 2%, w/v) and for different time periods (1 or 24 h) were prepared. The effect of the preparation variables was evaluated analysing the extent of crosslinking, the morphological aspect, the particle size and the swelling behaviour. To evaluate the pharmaceutical properties, an antihypertensive drug, clonidine hydrochloride, was chosen as drug model and loaded into the microspheres. Either the increase of the crosslinker concentration or of the crosslinking time period decreased both the swelling and the in vitro drug release processes of the microspheres. After the subcutaneous injection, the loaded microspheres crosslinked with the lowest GAL concentration (0.5%. w/v) or for the shortest time period (1 h) showed a reduction of systolic blood pressure (SBP) similar to that recorded with a clonidine hydrochloride solution having the same drug concentration. Instead, the microspheres crosslinked for 24 h with concentrations of GAL higher than 0.5% (w/v) produced a more gradual and sustained SEP reduction and the antihypertensive effect was maintained until 52-72 h. The biocompatibility studies showed that the microspheres crosslinked with GAL are well tolerated in vivo. These results suggest the potential application of gelatin microspheres crosslinked with GAL as a suitable drug delivery system for the subcutaneous administration. (C) 2001 Elsevier Science B.V. All rights reserved.

2001 - Histoplasma capsulatum var. capsulatum occurring in an HIV-positive Ghanaian immigrant to Italy - Identification of H-capsulatum DNA by PCR from paraffin sample [Articolo su rivista]
Rivasi, Francesco; B., Casali; A., Nanetti; G., Collina; A., Mazzoni
abstract

Histoplasmosis, which is highly endemic in the United States, is rare in Europe, usually imported but sometimes autochthonous. In Africa, histoplasmosis capsulati coexists with African histoplasmosis, a characteristic skin infection caused by H. capsulatum var. duboisii. Histoplamosis due to H. capsulatum is one of the 12 secondary infections listed in the surveillance definitions of AIDS. We report the case of a 36-year-old black man with acquired immunodeficiency syndrome (AIDS) who was living in Italy but originally came from Ghana. Histoplasmosis was disseminated with fever and cutaneous manifestations. The diagnosis was demonstrated morphologically based on the presence of yeast, observed by light microscopy, in skin lesions and by identification of H. capsulatum var. capsulatum DNA by nested PCR from a paraffin sample. No clinical reports of histoplamosis capsulati in Ghana have been published until now. The present case stresses the role of immigration of subjects from outside Europe who have been infected in their native country.

2001 - Pollinosi: l'analisi pollinica personalizzata è utile per la diagnosi e la prevenzione ? Studio pollinico e clinico di 10 pazienti (Modena, 1999). [Abstract in Atti di Convegno]
E., Martinelli; Trevisan, Giuliana; Mercuri, Anna Maria; Cf, Marchioni; Rivasi, Francesco; Accorsi, Carla Alberta
abstract

Campionamento personalizzato di poline diffuso in aria per pollinosici

2000 - Histopathological evidence of North American blastomycosis in Italy: report of two cases [Articolo su rivista]
Rivasi, Francesco; Nanetti, A; Cesinaro, Am; Mazzoni, A.
abstract

No clinical reports of blastomycosis in Italy have been published until now. We here report two cases of histologically diagnosed, unexpected cutaneous involvement in patients, aged 78 and 52 years, living in North Italy and never having been abroad. The histological differential diagnosis between blastomycosis and other fungal pathogens is discussed. Even in the absence of culture the present cases can confidently be considered as genuine examples of Blastomyces dermatitidis infection in Italy.

2000 - Human dirofilariasis due to Dirofilaria ( Nochtiella) repens: update of world literature from 1935 to 2000. [Articolo su rivista]
Pampiglione, S.; Rivasi, Francesco
abstract

Following on from their review of 1995 (Pampiglione et al.), the authors present an update of human cases of dirofilariasis due to Dirofilaria (Nochtiella) repens (Nematoda, Filarioidea, Onchocercidae) reported in the world literature. Cases of the parasitosis published from 1995 to 2000 are reported country by country. The essential data are presented in tabular form and the clinical, parasitological, histopathological, epidemiological features are analysed. 372 new cases spread over 25 countries are thus added to the list published in 1995. The countries most affected are Italy, Sri Lanka, some republics of the ex-Soviet Union. The age of the patients varied from 4 months to 100 years, the majority being in their 40s. There was virtually no difference in incidence between sexes. The parasite appeared most frequently in the upper half of the body, particularly in the head and ocular region and also in the upper limbs. Cases of visceral involvement are also reported. Of the various forms of human dirofilariasis, that due to D. (N.) repens is confirmed to be the most important as regards not only the number of subjects affected and the wide geographical distribution but also the variety of organs involved, notably the lungs, the male genitals and the female breast, invariably leading to a wrong diagnosis of malignant tumour. In man, the zoonosis may be described as emerging: whereas until the middle of the last century only a few dozen cases were reported, in the last 50 years the number has gradually increased to reach the present 782

2000 - The Italian experience of a Pap test and speculoscopy based screening programme [Articolo su rivista]
Boselli, F; De Martis, S; Rivasi, Francesco; Toni, A; Abbiati, R; Chiossi, G.
abstract

Objectives-The main objective of the study was to evaluate if speculoscopy, a magnified chemiluminescent examination, combined with a Pap smear, could improve the detection of early cervical lesions compared with the Pap smear alone. Setting-Pap tests and speculoscopies were performed in two family planning centres located in the surrounding areas of Modena. Colposcopic investigations and biopsies of the uterine cervix were performed in a second level centre (Gynaecological Prevention Centre of Modena Policlinico). Histological specimens were analysed at the Section of Pathological Anatomy of Modena Policlinico. Subjects-The study population comprised invited to undergo a Pap smear every three years in accordance with the screening programme for cervical cancer started in Modena in 1997. Methods-Midwives performed the Pap smear and speculoscopy in succession. Women with a positive Pap test and/or positive speculoscopy underwent colposcopy and, if colposcopic findings were positive, targeted punch biopsies were performed. Results-A total of 1000 patients were subjected to cytology and speculoscopy examinations. Among these women, 10 had abnormal Pap smear findings whereas 144 had an abnormal speculoscopic pattern. Only three of 59 patients with a histological diagnosis of cervical intraepithelial neoplasia grade I (CIN I)/human papillomavirus and only three of seven patients with CIN II/CIN III had a positive Pap test. Conclusions-Speculoscopy combined with a Pap test can significantly increase the detection of cervical lesions when included in a screening programme.

1999 - Carcinoid tumors of the lung: an analysis of 65 operated cases [Articolo su rivista]
Stefani, Alessandro; Morandi, Uliano; Urgese, Al; Rivasi, Francesco; Lodi, Renzo
abstract

Background The aim of this study was to analyse two groups of patients operated for bronchopulmonary neuroendocrine neoplasms (bronchial carcinoid and well-differentiated neuroendocrine carcinoma) and to investigate their clinico-pathological data and long-term survival. Methods. From January 1978 to June 1996, 65 patients with bronchial carcinoids underwent operation at our Institution. There were 33 males and 32 females, whose mean age was 49.8 years. Forty-four neoplasms (67.7%) were considered to be central. Histology revealed 54 typical bronchial carcinoids (83%) and 11 well-differentiated neuroendocrine carcinomas (17%), Surgical resection of tumor and complete lymph node dissection was performed in all cases, Results, All patients entered follow-up: 5-year survival was 91% for patients with bronchial carcinoid and 49% for those with well-differentiated neuroendocrine carcinoma (p<0.05). Univariate analysis found that there was a significant decrease in survival also for peripheral location of the tumor, advanced pathologic stage and histologically positive lymph nodes. Conclusions. These results point out that carcinoid tumors are malignant neoplasms, so they require a complete and radical surgical resection, Most tumors are only locally invasive and show a low aggressive behaviour; therefore, when possible, it is recommended to attempt a limited resection, Frozen sections of bronchial margins and complete lymphadenectomy should be routinely performed. The same criteria should apply to well differentiated neuroendoctine carcinomas, though their behaviour is more aggressive.

1999 - Pitfalls and difficulties in histological diagnosis of human dirofilariasis due to Dirofilaria (Nochtiella) repens [Articolo su rivista]
Pampiglione, S; Rivasi, Francesco; Canestri Trotti, G.
abstract

The authors have conducted a histologic study of over 90 cases of Dirofilaria infection in man due to Dirofilaria repens, the most extensive study of its kind in the would. On the basis of their findings, they illustrate the diagnostic difficulties that may arise when regreessive phenomena I ender the parasite´s morphologic characteristics largely or completely unrecognizable. These phenomena are due to the death of the filaria inside the inflammatory nodule weeks ol months prior to surgical removal, and to the consequent invasion of inflammatory cells. They start at the nenatode´s natural orifices (mouth, vulva, anus, cloaca) and gradually spread throughout ifs body. In cases of difficult diagnosis, therefore, it is recommended that rite nodule be sectioned at different points comprising caudal, cephalic and middle body aspects, so as to reveal the Jew morphologic features that ale still recognizable and which may afford a correct diagnosis. The authors present examples of histologic sections in color plates in which the nematode was in an excellent state of preservation and others illustrating the full range of regressive phenomena, from slight to total disintegration of the bodily structure.

1999 - Pregnancy luteoma with granulosa cell proliferation: An unusual hyperplastic lesion arising in pregnancy and mimicking an ovarian neoplasia [Articolo su rivista]
Piana, S; Nogales, Ff; Corrado, S; Cardinale, L; Gusolfino, D; Rivasi, Francesco
abstract

A pregnancy luteoma (PL) was incidentally found at a term cesarean section in a 27-year-old black woman without any endocrine abnormality. The lesion involved only the left ovary; it had a nodular and focal pseudoalveolar growth pattern and was associated with areas of tubular sertoliform component, consistent with granulosa cell proliferation. Immunohistochemistry revealed a diffuse positivity to Inhibin A, CD99, cytokeratin and vimentin. The ultrastructure was typical of steroid-producing cells. PL is a tumor-like lesion arising in pregnant women and often misdiagnosed as a neoplastic lesion; awareness of this rare entity and its differential diagnoses may avoid unnecessary surgery in young patients.

1998 - Gastric involvement in AIDS associated cryptosporidiosis [Articolo su rivista]
Rossi, P; Rivasi, Francesco; Codeluppi, M; Catania, A; Tamburrini, A; Righi, E; Pozio, E.
abstract

Background-Cryptosporidiosis has been shown to be a common cause of diarrhoea in both immunocompetent and immunosuppressed individuals. There are very few data on the distribution of Cryptosporidium parvum along the gastro-intestinal tract. Aims-To evaluate the location of Cryptosporidium parasites in the digestive tract of patients with AIDS. Methods-Gastrointestinal localisation of C parvum was studied in 71 patients with AIDS who underwent upper and/or lower endoscopy with biopsy for chronic diarrhoeal illness and/or other gastrointestinal disorders of unexplained origin. Results-Twenty four individuals (33.8%) were positive for C parvum, of which 16 (85.9%) had parasites in the gastric epithelium, Most patients with gastric localisation of C parvum did not show specific symptoms indicating the presence of this parasite in the stomach. Conclusions-Gastric involvement in AIDS related cryptosporidiosis is more frequent than expected, but no clear correlation between gastric location and related clinical and pathological features was observed.

1997 - Cryptic infection by whipworm mimicking a sessile polyp of the colon [Articolo su rivista]
Pampiglione, S; Rivasi, Francesco; Rubbiani, C.
abstract

A case of trichocephaliasis in a 70-year-old male is described. The original diagnosis, based on radiological and endoscopic findings, was of a sessile polyp of the colon. Only when a fragment of the supposed polyp was removed at biopsy and examined histologically was it revealed as a single male specimen of whipworm.

1996 - Histiocytic endometritis [Articolo su rivista]
Rivasi, Francesco; E., Philippe
abstract

Two cases of histiocytic endometritis are reported in two 68 and 82 year-old women. One of the cases was associated with extensive endometrioid adenocarcinoma and areas of intra-myometrial histiocytic infiltration.

1996 - Human dirofilariasis in Greece: A review of reported cases and a description of a new, subcutaneous case [Articolo su rivista]
Pampiglione, S; Trotti, Gc; Rivasi, Francesco; Vakalis, N.
abstract

A superficial analysis of Greek reports of human cases of dirofilariasis indicated that this zoonosis is rare in Greece. However, a more detailed review of the international literature revealed several more cases, diagnosed and recorded in other countries following infection during holidays in Greece. Overall, at least 20 individuals are now known to have been infected in Greece, in all regions of the country. A new, subcutaneous case of dirofilariasis is described; the infection occurred in a 45-year-old male living in Piraeus (Athens), and was localized in the abdominal wall. Histology revealed a female Dirofilaria (Nochtiella) repens in the reactive nodule.

1996 - Human pulmonary dirofilariasis [Articolo su rivista]
Pampiglione, S; Rivasi, Francesco; Paolino, S.
abstract

Two new cases of human pulmonary dirofilariasis, in a 66-year-old woman and a 69-year-old man, respectively, both living in the Po valley, are described. They represent the 7th and 8th cases reported in Italy and seem to be ascribable to Dirofilaria repens, even though the poor state of preservation of the parasites did not allow the morphology of the species involved to be clearly defined. In both cases, the false clinical diagnosis of lung cancer was based on the accidental radiological discovery of a coin lesion, the nematodes being located in a pulmonary artery producing a small, roundish infarct.

1996 - Ovarian angioma: Three asymptomatic cases. [Articolo su rivista]
Rivasi, Francesco; Philippe, E; Walter, P; Demarco, L; Ludwig, L.
abstract

In 3 female patients, aged 46, 50 and 74 years respectively, ovarian angiomas measuring 3, 5 and 30 mm in diameter were discover-ed. All the angiomas were asymptomatic. They were either associated with endometrioid carcinoma or uterine leiomyomas, or detected casually by ultrasound scan in a patient with ascites, intrahepatic nodule and increased serologic CA 125. The immunohistochemical studies failed to reveal any affinity between the vascular endothelium of our ovarian angiomas and oestrogen and progesteron receptors.

1995 - CYTOLOGIC DIAGNOSIS OF ACANTHAMOEBA-KERATITIS - REPORT OF A CASE WITH CORRELATIVE STUDY WITH INDIRECT IMMUNOFLUORESCENCE AND SCANNING ELECTRON-MICROSCOPY [Articolo su rivista]
Rivasi, Francesco; Longanesi, L; Casolari, Chiara; Croppo, Gp; Pierini, G; Zunarelli, E; Visvesvara, G. S.
abstract

We describe a case of Acanthamoeba keratitis in a 20-year-old woman who wore disposable soft contact lenses. The diagnosis was made initially on the basis of a periodic acid-Schiff-stained corneal smear and subsequently confirmed by scanning electron microscopy and immunofluorescence. The patient was successfully treated with a combination of 0.053% polyhexamethylene biguanide and miconazole. Cytologic study and culture of corneal scrapings is relatively painless and inexpensive and may therefore be used for successful diagnosis and follow-up.

1995 - Gastric localization of Leishmania in a patient with acquired immunodeficiency syndrome. A case report [Articolo su rivista]
L., Gradoni; Guaraldi, Giovanni; M., Codeluppi; A., Scalone; Rivasi, Francesco
abstract

We report a case of gastric localization of Leishmania in a 29-year old man affected by AIDS. Gastric biopsies revealed macrophages infected with intracytoplasmic organisms attributable to Leishmania amastigotes. The authors emphasize the importance of performing random biopsies in the absence of endoscopic abnormalities.

1994 - PULMONARY DIROFILARIASIS IN MAN - A NEW ITALIAN CASE, REVIEW OF THE EUROPEAN LITERATURE [Articolo su rivista]
Pampiglione, S; Delmaschio, O; Pagan, V; Rivasi, Francesco
abstract

In June 1991 a 62-year-old retired mon, from Udine (northern Italy), was suddenly affected by dyspnoea. X-ray and CT control detected a coin lesion in the lung. In May 1992 this lesion was removed surgically. Histological examination revealed the presence of a nematode inside an arteriole which had provoked a small infarct in the pulmonary tissue. The parasite presented marked regressive phenomena that made on accurate morphological analysis impossible. However, in the light of certain details oi the cuticle, and by analogy with lour similar cases occurring in northern Italy, as well as 10 others (nine subcutaneous and one sub-mucosal) reported in man from the same region (Venetia) over the last 15 years, the aetiologic agent was thought io be Dirofilaria (N.) repens. Over all 10 cases of human pulmonary dirofilariasis were reported in Europe : five in Italy, probably by D.(N.) repens, two in Germany, in patients coming from Corsica and two in Spain (only by serology), attributed io D. immitis. In addition one case was reported in U.S.A. in a man who previously visited Italy.

1993 - Infezioni cervico-vaginali da Chlamydia trachomatis in un campione di donne asintomatiche: confronto di quattro differenti [Articolo su rivista]
Messi, Patrizia; Rivasi, Francesco; Fabio, A.; Provvisionato, Alberto; Turci, M.
abstract

In campioni cervico-vaginali di 150 donne asintomatiche sono state messe a confronto 4 metodiche in uso per la ricerca di Chlamydia trachomatis. I risultati hanno confermato che l'immunofluorescenza diretta rappresenta la tecnica in grado di rilevare il maggior numero di casi positivi anche in assenza di sintomi

1992 - KERATOMYCOSIS WITH AN UNUSUAL ETIOLOGY (RHODOTORULA-GLUTINIS) - A CASE-REPORT [Articolo su rivista]
Casolari, Chiara; Nanetti, A; Cavallini, Gian Maria; Rivasi, Francesco; Fabio, U; Mazzoni, A.
abstract

A case of deep keratomycosis with isolation of Rhodotorula glutinis is discussed. Keratoplasty, done immediately, prevented panophtalmitis and cured the patient. The etiology and pathogenesis of fungal keratitis is examined.

1992 - RHODOTORULA-GLUTINIS KERATITIS [Articolo su rivista]
Guerra, R; Cavallini, Gian Maria; Longanesi, L; Casolari, Chiara; Bertoli, G; Rivasi, Francesco; Fabio, U.
abstract

The authors report a case of deep keratomycosis, revealed by penetrating keratoplasty to be due to Rhodotorula glutinis.

1989 - Chlamydia trachomatis infections in asymptomatic women. Results of a study employing different staining techniques [Articolo su rivista]
Ghirardini, Carla; Boselli, F; Messi, Patrizia; Rivasi, Francesco; Trentini, G. P.
abstract

A total of 300 cervical smears randomly collected from asymptomatic women in a mass-screening program for the detection of cervical carcinoma was investigated for Chlamydia trachomatis infection by the use of Papanicolaou and immunofluorescence staining. Features of chlamydial infection detected in 18 cases by Papanicolaou-stained smears were confirmed in 11 cases with immunofluorescence; not a single case that was negative in the Papanicolaou-stained smears was positive by immunofluorescence. The presence of Chlamydia in the Papanicolaou-stained smears in ten cases, including two cases that were negative by immunofluorescence, was also proven by either immunoperoxidase staining or in situ hybridization. On the other hand, either immunoperoxidase or in situ hybridization gave false-negative results in two of the ten cases. Therefore, the combined use of different techniques demonstrated that false-negative results occurred with all techniques, except with Papanicolaou-stained smears, whose sensitivity is apparently the highest.

1987 - Su di un caso di Morbo di Hodgkin complicato da infestazione da Strongyloides Stercoralis [Articolo su rivista]
Dini, D.; Rivasi, Francesco; Federico, Massimo; Casolari, C.; Barbieri, F.
abstract

Viene riferito un caso di Morbo di Hodgkin complicato da grave infestazione da Strongyloides stercoralis. Lo Strongyloides è un parassita opportunista in grado di determinare quadri clinici particolarmente gravi, per autoinfestazione, in condizioni di immunodepressione. In questi pazienti la comparsa di sintomi gastrointestinali aspecifici deve indurre ad eseguire gli accertamenti necessari per evidenziare, accanto ai più comuni germi patogeni, anche la presenza di parassiti.

1973 - Regulation of cholesterol biosynthesis in rat liver after the administration of N-2-fluorenylacetamide [Articolo su rivista]
CALANDRA BUONAURA, Sebastiano; Guariento, D; Rivasi, Francesco
abstract

No abstract available