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lo studio ha confrontato le funzioni esecutive di pazienti con disturbi psicotici coinvolti in programmi riabilitativi in Strutture Residenziali di Palermo. Metodi: sono stati reclutati 16 utenti di Comunità Alloggio (CA) e 14 utenti di Comunità Terapeutiche Assistite (CTA), tra 18 e 65 anni, valutati tramite somministrazione di Trail Making Test(TMT), Wisconsin Card Sorting Test (WCST), Frontal Assessment Battery (FAB), Stroop Test, 4 subtest della WAIS-R e Brief Psychiatric Rating Scale (BPRS). Risultati: i due campioni presentano caratteristiche sociodemografiche omogenee. Gli utenti delle CTA fanno rilevare maggiore uso di neurolettici (73,3% vs. 18.8% p 0,004) e un trend non significativo di minore espressività sintomatologica (BPRS: 2,39 vs. 2,58); essi, inoltre, sono maggiormente coinvolti in interventi riabilitativi avanzati con uso di tecniche cognitive (40,0% vs. 6,3% p 0,037) ed espressive (83,3% vs. 16,7% p 0,000) e presentavano migliori prestazioni cognitive al FAB(p 0,048), agli Errori Perseverativi del WCST(p 0,000) e allo Stroop Test(p 0,027). Conclusioni: l’analisi dei risultati suggerisce che gli utenti delle CA presentano deficit in differenti domini cognitivi, maggiore difficoltà a distribuire l’attenzione tra più compiti simultanei e scarsa flessibilità cognitiva, riconducibile a storia clinica e durata di trattamento antipsicotico più datati. Pertanto, la maggiore partecipazione degli utenti delle CTA in training riabilitativi intensivi,cognitivi ed espressivi, potrebbe spiegare il più efficace recupero delle funzioni esecutive studiate. Bibliografia Addington J, Girard TA, Christensen BK, et al. Social cognition mediates illness-related and cognitive influences on social function in patients with schizophrenia-spectrum disorders. J Psychiatry Neurosci 2010;35:49-54. McGurk SR, Mueser KT. Cognitive functioning,symptoms, and work in supported employment: an review and heuristic model. Schizophr Res 2004;70:147-73. Krabbendam L, Aleman A. Cognitive rehabilitation in schizophrenia: a quantitative analysis of controlled

Since the activity of several conventional anticancer drugs is restricted by resistance mechanisms and dose-limiting side-effects, the design of formulations for local application on malignant lesions seems to be an efficient and promising drug delivery approach. In this study, the effect of locally applied 5-FU on cell death was evaluated both in a SCC4/HEK001 model and in a newly proposed 3D outgrowth model of oral squamous cell carcinoma (OSCC). Initially, the optimal drug dose was established by delivery of solutions containing different amounts of 5-FU. The solution containing 1% (w/v) of 5-FU resulted effective in inducing cell death with complete eradication of cell colonies. Buccal tablets were designed to deliver 5-FU locoregionally to the cancer lesions of the oral cavity. Tablets were prepared using a drug loaded matrix of acrylic/methacrylic acid copolymer containing 1% (w/w) of 5-FU and applied on 3D outgrowths. The drug release from tablets appeared to be sufficient to induce cell death as confirmed by transmission electron microscopy and enzymatic assay (TUNEL). After 120 h of treatment, when about 90% of the drug had been discharged from the tablets into the culture environment, 5-FU caused loss of cell-cell communications and apoptotic cell death. After 192 h, a complete disaggregation of the 3D oral outgrowths and the death of all the cells was observed. Buccal matrix tablets could be considered a promising new approach to the locoregional treatment of OSCC. Risks of systemic toxicity are avoided since very low drug doses are delivered.

Una buona capacità di insight pare costituire un fattore predittivo di minore espressività psicopatologica nei pazienti affetti da psicosi. In questo lavoro intendiamo analizzare le relazioni tra grado di insight e gravità dei sintomi psicotici utilizzando i punteggi totali e parziali ottenuti alla Positive and Negative Syndrome Scale (PANSS) in un gruppo di pazienti affetti da psicosi all'esordio nell'ambito del progetto SGAP "Sicilian Genetic and Psychosis" svolto in collaborazione con il GAP Study dell'Institute of Psychiatry, King's College of London.

Introduzione: la durata di psicosi non trattata (DUP) nei pazienti affetti da psicosi all’esordio rappresenta un fattore predittivo dell’outcome e del decorso del disturbo (Perkins, 2005). La relazione tra consumo di cannabis e DUP è ancora controversa. In questo lavoro viene analizzato il rapporto tra DUP ed età di esordio, consumo di cannabis, funzionamento cognitivo, livello di istruzione e stato di occupazione in un gruppo di pazienti affetti da psicosi all’esordio reclutati nell’ambito dello studio SGAP (Sicilian Genetic and Psychosis) svolto in collaborazione con l’Institute of Psychiatry, King's College of London. Metodologia: sono stati reclutati 74 pazienti di età compresa tra 18 e 65 anni ai quali è stata somministrata una batteria di test composta da: Nottingham Onset Schedule (NOS-DUP), Positive and Negative Syndrome Scale (PANSS) , Social Data Schedule, Cannabis Experience Questionnaire (CEQ), WAIS-R. Risultati: il campione, ancora in fase di reclutamento, è costituito da 74 pazienti (M=68,9%), età media 26,39 (DS=9,36). La durata media di psicosi non trattata è di 40,4 settimane, il 39,5%, dei pazienti ha fatto uso di cannabis nel periodo immediatamente precedente il ricovero. Nel nostro campione i pazienti che fanno uso di cannabis hanno una DUP più breve (p=0,023) e afferiscono ai servizi di salute mentale in età più precoce (p=0,064) rispetto ai non consumatori. Inoltre vi è una correlazione inversa tra DUP e QI (p=0,05). Non sono al momento emerse correlazioni significative tra DUP e severità dei sintomi, valutati attraverso la PANSS. Conclusioni: i nostri risultati, in linea con i dati di letteratura, supportano l’associazione tra consumo di cannabis ed esordio precoce dei sintomi psicotici. Inoltre il consumo di cannabis si associa ad una minore durata della DUP ma quest’ultimo dato sembra meritevole di ulteriori indagini.

The morphological aspects of Styela plicata fertilization after treatment with tributyltin(IV) chloride are described by means of scanning and transmission electron microscopy investigations. Alterations have been shown both on female and male gametes; spermatozoa, all the egg envelopes and the mitochondria of the egg cortical cytoplasm are modified in relation to incubation time. As a consequence, the damage to gametes blocks sperm-egg interaction and fertilization does not occur. Copyright © 2003 John Wiley & Sons, Ltd.

The importance of the pericardium and the pericardial fluid (PF) in the control of cardiac function has emerged over the past few years. Despite the acknowledgment that amphibians are exposed to both dehydration and excessive water accumulation, nothing is known about their pericardial structure and the morphological basis of the PF formation. We have studied the parietal pericardium (PP) morphology in Rana esculenta by electron microscopy. SEM images of the inner surface, which lines the pericardial cavity, revealed the presence of large vesicles and many small circular openings. TEM observations showed that the PP is made up of an inner mesothelial lining, often constituted by two layers of very flat cells lying on a basal membrane and of regularly oriented collagen bundles. The PP outer surface is lined by a layer of flat cells, without a basal membrane. The mesothelial cells had overlapping boundaries with complex intercellular connections and a rich pool of caveolae opened in the direction of both the pericardial cavity and intercellular spaces. These cells indicate an intense intracellular and/or intercellular transfer of fluids and substances. The intraperitoneal injection of the idromineral hormone, Val5-ANG II, induced PP modifications, particularly evident at the level of the structures involved in the transmesothelial traffic. These lymphatic-like traits suggest that the frog PP represents a large lymphatic sac, subject to paracrine-endocrine remodeling, which can actively adjust the PF, influencing the composition and volume of the myocardial interstitial fluid. © 2003 Wiley-Liss, Inc.

Apoptosis is considered an important mechanism of selective deletion that occurs during hematopoiesis. Myelolipoma is a rare benign tumor composed of adipose tissue and hematopoietic cells. The pathogenesis of this benign tumor is still unclear. Analysing the structural levels and apoptosis of normal human bone marrow (NHBM) and human myelolipoma (HM), the apoptotic events resulted abundantly present in NHBM compared to HM, which showed a small number of apoptotic cells. By contrast, Fas expression was strongly present both in NHBM and HM. These findings suggest that an altered function of Fas in myelolipoma is not able to trigger the apoptotic machinery. In conclusion, we hypothesize that drastic reduction of apoptosis in myelolipoma can be considered one of the growth regulatory mechanisms.

The limited and inadequate availability of organs from human donors has resulted in the utilisation of xenografts as an alternative tool. Nevertheless, hyperacute rejection (HAR) following xenograft determines the loss of the transplanted organ. The “primum movens” is the activation of the complement pathway mediated by the binding of natural xenogenic antibodies to the endothelium of the graft, followed by the lysis of the endothelial cells with subsequent oedema, thrombosis and necrosis of the transplanted organ. In this work we describe morphological and biomolecular observations of isolated human-decay accelerating factor (h-DAF, CD55) transgenic pig hearts, after perfusion for four hours with human blood. H-DAF is a membrane glycoprotein inhibiting the complement activation in humans. We describe considerably reduced damages in transgenic hearts, compared to controls. The cardiac function resulted preserved. Our data are in agreement with what was already shown by other groups using different experimental models. In conclusion, we encourage the use of new sources of transgenic animals, pointing out the importance of morphological analysis in evaluation of xenograft.

In this work we studied the inguinal-abdominal region and the inguinal canal using three-dimensional geometrical models. We built the models through computer aided geometric modeling techniques on the basis of observations during real dissections, operations and diagnostic medical imaging. The obtained models show in a complete modular synthesis and with a schematic iconology the structural organization of the anatomical districts in a logic sequence of layers and topographic and spatial relationships among its components. The models represent an amazing support to anatomy and clinical anatomy for teaching and research purposes on organogenesis, surgery and diagnosis.

Background/Aim: Epithelial-mesenchymal communication plays a key role in tissue homeostasis and abnormal signaling contributes to chronic airways disease such as COPD. Most in vitro models are limited in complexity and poorly represent this epithelial-mesenchymal trophic unit. We postulated that cellular outgrowth from bronchial tissue would enable development of a mucosal structure that recapitulates better in vivo tissue architecture. Materials and Methods: Bronchial tissue was embedded in Matrigel and outgrowth cultures monitored using time-lapse microscopy, electrical resistance, light and electron microscopy. Cultures were challenged repetitively with cigarette smoke extract (CSE). Results: The outgrowths formed as a multicellular sheet with motile cilia becoming evident as the Matrigel was remodeled to provide an air interface; cultures were viable for more than one year. Immunofluorescence and electron microscopy (EM) identified an upper layer of mucociliary epithelium and a lower layer of highly organized extracellular matrix (ECM) interspersed with fibroblastic cells separated by a basement membrane. EM analysis of the mucosal construct after repetitive exposure of to CSE revealed epithelial damage, loss of cilia, and ECM remodeling, as occurs in vivo.Conclusions: We have developed a robust bronchial mucosal model. The structural changes observed following CSE exposure suggest the model should have utility for drug discovery and preclinical testing, especially those targeting airway remodeling.

The knowledge and treatment of alcoholic liver disease is still plagued with gaps mostly due to the inherent limitations of research with patients. We developed an animal model for studying liver histopathology, Hsp-chaperones involvement, and response to treatment. The system was standardized using mice to which ethanol was orally administered alone or in combination with Lactobacillus fermentum for 4, 8 and 12 weeks and applying a battery of techniques (histology, immunohistochemistry, Western blotting, real-time PCR, immunoprecipitation, 3-nitrotyrosine labeling) to assess liver pathology and Hsp60, iNOS gene expression and protein levels, and Hsp60 post-translational modifications. Steatosis score, iNOS levels, and nitrosylated proteins (e.g., Hsp60) decreased after probiotic intake reducing considerably ethanol-induced tissue damage. However, one may assume that the probiotic tested has a gut protective effect and, possibly, anti-steatotic and antioxidant effects in the liver. Our results provide novel insights that may be taken into account while devising new approaches for treating liver diseases associated with alcohol consumption (1)., Italian Journal of Anatomy and Embryology, Vol. 121, No. 1 (Supplement) 2016

Objectives Alcoholism is one of the most devastating diseases with high incidence, but knowledge of its pathology and treatment is still plagued with gaps mostly because of the inherent limitations of research with patients. We developed an animal model for studying liver histopathology, Hsp (heat-shock protein)-chaperones involvement, and response to treatment. Methods The system was standardized using mice to which ethanol was orally administered alone or in combination with Lactobacillus fermentum following a precise schedule over time and applying, at predetermined intervals, a battery of techniques (histology, immunohistochemistry, western blotting, real-time PCR, immunoprecipitation, 3-nitrotyrosine labeling) to assess liver pathology (e.g., steatosis, fibrosis), and Hsp60 and iNOS (inducible form of nitric oxide synthase) gene expression and protein levels, and post-translational modifications. Results Typical ethanol-induced liver pathology occurred and the effect of the probiotic could be reliably monitored. Steatosis score, iNOS levels, and nitrated proteins (e.g., Hsp60) decreased after probiotic intake. Conclusions We describe a mouse model useful for studying liver disease induced by chronic ethanol intake and for testing pertinent therapeutic agents, e.g., probiotics. We tested L. fermentum, which reduced considerably ethanol-induced tissue damage and deleterious post-translational modifications of the chaperone Hsp60. The model is available to test other agents and probiotics with therapeutic potential in alcoholic liver disease.

In the last few years, a major goal of cardiac research has been to drive stem cell differentiation to replace damaged myocardium. Several research groups have attempted to differentiate potential cardiac stem cells (CSCs) using bi- or three-dimensional systems supplemented with growth factors or molecules acting as differentiating substances. We hypothesize that these systems failed to induce a complete differentiation because they lacked an architectural space. In the present study, we isolated a pool of small proliferating and fibroblast-like cells from adult rat myocardium. The phenotype of these cells was assessed and the characterized cells were cultured in a collagen I/OPLA scaffold with horse serum to obtain fine myocardial differentiation. C-Kit(POS)/Sca-1(POS) CSCs fully differentiated in vitro when an environment more similar to the CSC niche was created. These experiments demonstrated an important model for the study of the biology of CSCs and the biochemical pathways that lead to myocardial differentiation. The results pave the way for a new surgical approach.

Italian Journal of Anatomy and Embryology, Vol 115, No 1/2 (Supplement) 2010

Background Hsp60, a Group I mitochondrial chaperonin, is classically considered an intracellular chaperone with residence in the mitochondria; nonetheless, in the last few years it has been found extracellularly as well as in the cell membrane. Important questions remain pertaining to extracellular Hsp60 such as how generalized is its occurrence outside cells, what are its extracellular functions and the translocation mechanisms that transport the chaperone outside of the cell. These questions are particularly relevant for cancer biology since it is believed that extracellular chaperones, like Hsp70, may play an active role in tumor growth and dissemination. Methodology/Principal Findings Since cancer cells may undergo necrosis and apoptosis, it could be possible that extracellular Hsps are chiefly the result of cell destruction but not the product of an active, physiological process. In this work, we studied three tumor cells lines and found that they all release Hsp60 into the culture media by an active mechanism independently of cell death. Biochemical analyses of one of the cell lines revealed that Hsp60 secretion was significantly reduced, by inhibitors of exosomes and lipid rafts. Conclusions/Significance Our data suggest that Hsp60 release is the result of an active secretion mechanism and, since extracellular release of the chaperone was demonstrated in all tumor cell lines investigated, our observations most likely reflect a general physiological phenomenon, occurring in many tumors.

The human foot is considered an organ with an assortment of tissues with different morphological characteristics and well defined limits, but effectively has a simple functionality when static that becomes extremely complex when in movement. Its complex structure, comprised of an elastic and resistant skin covering a bone framework, joints, muscles, tendons, veins and nerves, can be compared to an efficient mechanical assembly. After a long and extraordinary evolutive journey, the human foot has undergone numerous changes to perfect its function; it has lost most of its grabbing function whilst gaining new characteristics that have ultimately allowed the modern man to stand upright. The complex articular structure of the human foot consists of thirty four synovial joints, of which eighteen have curved surfaces and sixteen plane surfaces. Following the criteria set by the systematic, radiological and clinical anatomy, the Authors contribute further to the current knowledge on the ankle, tarsal (anatomic subtalar, transverse tarsal, cuneonavicular, intercuneiform and cuneocuboid), tarsometatarsal, intermetatarsal, metatarsophalangeal and interphalangeal joints and dorsal, plantar and interosseous ligaments of the human foot. The articular lines of the transverse tarsal (Chopart) and tarsometatarsal (Lisfranc) joints are particularly interesting and not only from a surgical point of view; through a straightforward identification of few reference points, it is possible to find the medial and lateral extremities of the Chopart's and Lisfranc's lines, the former pinpoints the boundary between the hindfoot and midfoot and the latter between the midfoot and forefoot.

The aim of the present study was to evaluate the expression of the heat shock protein 60 (HSP60), a mitochondrial matrix-associated protein belonging to the chaperonin family, in colorectal adenomas and cancers, comparing them to normal colonic tissues and hyperplastic polyps. We performed both immunohistochemistry and Western blot analysis for HSP60. Immunohistochemistry resulted positive in all tubular adenomas and infiltrating adenocarcinomas. By contrast, normal tissues and hyperplastic polyps were negative. Quantitative analysis showed that tubular adenomas with different levels of dysplasia did not present statistical differences concerning HSP60 positivity. In addition, carcinomas always showed the highest expression. Western blot analysis confirmed these observations. These data suggest that HSP60 over-expression is an early event in carcinogenesis. We suspect that HSP60 plays a different role in colorectal carcinogenesis with respect to that in normal cells, which foresees its possible use as diagnostic and prognostic tools.