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Objective Different surgical approaches have been used over the years in order to access skull base. The endoscopic endonasal approach represents a direct and minimally invasive approach to the suprasellar, retrosellar, and retroclival space, with the advantage of avoid brain retraction and visualize safely and effectively the surgical target. The present contribution aims to provide anatomical details of the skull base as seen from below (i.e., via an endoscopic endonasal approach). Methods Five human cadaver heads were dissected. The anatomical neurovascular structures within the skull base were visualized and carefully described from an endoscopic endonasal view. The advantages and limitations of the endoscopic endonasal route were discussed as well. Results The entire skull base region, as seen from the endoscopic endonasal viewpoint, has been divided in 4 main regions: anterior skull base, middle skull base, posterior skull base and parasellar area. Conclusion The development of endoscopic techniques has opened different perspectives over the skull base surgery. Endonasal surgery provides access to a wide range of skull base lesions via a natural surgical corridor (i.e., the nasal cavities).

Cross talk between unrelated cell surface receptors, such as G-protein-coupled receptors (GPCR) and receptor tyrosine kinases (RTK), is a crucial signaling mechanism to expand the cellular communication network. We investigated the ability of the GPCR formyl peptide receptor-like 1 (FPRL1) to transactivate the RTK epidermal growth factor receptor (EGFR) in CaLu-6 cells. We observed that stimulation with WKYMVm, an FPRL1 agonist isolated by screening synthetic peptide libraries, induces EGFR tyrosine phosphorylation, p47(phox) phosphorylation, NADPH-oxidase-dependent superoxide generation, and c-Src kinase activity. As a result of EGFR transactivation, phosphotyrosine residues provide docking sites for recruitment and triggering of the STAT3 pathway. WKYMVm-induced EGFR transactivation is prevented by the FPRL1-selective antagonist WRWWWW, by pertussis toxin (PTX), and by the c-Src inhibitor PP2. The critical role of NADPH-oxidase-dependent superoxide generation in this cross-talk mechanism is corroborated by the finding that apocynin or a siRNA against p22(phox) prevents EGFR transactivation and c-Src kinase activity. In addition, WKYMVm promotes CaLu-6 cell growth, which is prevented by PTX and by WRWWWW. These results highlight the role of FPRL1 as a potential target of new drugs and suggest that targeting both FPRL1 and EGFR may yield superior therapeutic effects compared with targeting either receptor separately.

Postischemic cardiomyopathy remains one of the disorders in urgent need of effective noninvasive therapy. It is currently accepted that the isolation, expansion and application of resident cardiac stem cells may hold therapeutic promise for the future. Recently, it has been demonstrated that shock waves (SW) could enhance the expression of vascular endothelial growth factor (VEGF) and its receptor, Flt-1. As the development of angiogenic noninvasive therapy is very important for future therapeutic strategies in cardiovascular diseases, we examined in vitro, the effects of SW treatment on adult resident cardiac primitive cells isolated from bioptic fragments of normal human hearts and from explanted pathologic hearts with postischemic cardiomyopathy. This study demonstrates that SW have positive influence on both the proliferation and the differentiation of cardiomyocytes, smooth muscle and endothelial cells precursors, with a more obvious effect being evident in the cells from normal heart than in those taken from pathologic hearts. Our results suggest that SW treatment could inhibit or retard the pathologic remodeling and functional degradation of the heart if applied during the early stages of heart failure.

Chondrocytes have been shown to express both in vivo and in vitro a number of integrins of the beta1-, beta3- and beta5-subfamilies (Biorheology 37 (2000) 109). Normal and v-Src-transformed chick epiphyseal chondrocytes (CEC) display different adhesion properties. While normal CEC with time in culture tends to increase their adhesion to the substrate by organizing focal adhesions and actin stress fibers, v-Src-transformed chondrocytes display a refractile morphology and disorganization of actin cytoskeleton. We wondered whether the reduced adhesion and spreading of v-Src-transformed chondrocytes could be ascribed to changes in integrin expression and/or function. Integrin expression by normal CEC is studied and compared to v-Src-transformed chick chondrocytes, using monoclonal and polyclonal antibodies to integrins alpha- and beta-chains. We show the presence of alpha1-, alpha3-, alphav-, alpha6-, beta1- and beta3-chains on CEC, with very low levels of alpha2- and alpha5-chains. Alphav chain associates with multiple beta subunits in normal and transformed chondrocytes. With the exception of alpha1- and alpha2-chains, the levels of the integrin chains analyzed are higher in transformed chondrocytes as compared with normal chondrocytes. In spite of the increased levels of integrin expression, transformed chondrocytes exhibit loss of focal adhesion and actin stress fibers and low adhesion activity on several extracellular matrix constituents. These observations raise the possibility that, in addition to its effects on global pattern of integrin expression, v-Src can influence integrin function in chondrocytes.

Use of resorbable external reinforcement of the pulmonary autograft during the Ross operation has been suggested, but the differential regional potential for dilation of the aorta, mainly regarding the neo-root and the neo-Valsalva sinuses, represents an unresolved issue. Auxetic materials could be useful in preventing dilation given their favorable mechanical properties. We designed a composite semiresorbable armoured bioprosthesis constituted by polydioxanone and expanded polytetrafluoroethylene and evaluated its effectiveness as a pulmonary autograft reinforcement device in an animal model of the Ross procedure.An experimental model of the Ross procedure was performed in 20 three-month-old growing lambs. The pulmonary autograft was alternatively nonreinforced (control group n = 10) or reinforced with composite bioprosthesis (reinforced group n = 10). Animals were followed up during growth for 6 months by angiography and echocardiography. Specific stainings for extracellular matrix and immunohistochemistry for metalloproteinase-9 were performed.Reference aortic diameter increased from 14 ± 1 mm to 19 ± 2 mm over 6 months of growth. In the control group, pulmonary autograft distension (28 ± 2 mm) was immediately noted, followed by aneurysm development at 6 months (40 ± 2 mm, P.001 vs reference). In the reinforced group, an initial dilation to 18 ± 1 mm was detected and the final diameter was 27 ± 2 mm (42% increase). Two deaths due to pulmonary autograft rupture occurred in the control group. On histology, the control group showed medial disruption with connective fibrous replacement, whereas in the reinforced group compensatory intimal hyperplasia was present in the absence of intimal tears. The bioprosthesis promoted a positive matrix rearrangement process favoring neoarterialization and elastic remodeling as demonstrated on specific staining for elastin collagen and metalloproteinase-9.The device adapted and functionally compensated for the characteristics of autograft growth, guaranteeing a reasonable size of the autograft at 6 months, but more important, because the device is biocompatible, it did not disrupt the biological process of growth or cause inflammatory damage to the wall.

OBJECTIVE: The present study examined temporal and spatial patterns of extracellular matrix and smooth muscle cell changes in the ascending aorta with bicuspid and tricuspid aortic valve stenosis. METHODS: Wall specimens were retrieved from both the greater and the lesser curvature ("convexity" and "concavity") of 14 nonaneurysmal and 12 aneurysmal aortas (aortic ratios 1.2 and 1.5, respectively) and from 3 heart donors (normal). Immunochemistry was performed for detection of apoptotic (terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling [TUNEL]-positive) and proliferating (Ki-67-positive) smooth muscle cells and for semiquantification of matrix proteins (collagens, fibronectin, tenascin, laminin). Co-immunoprecipitation assessed the extent of Bcl-2-modifying factor binding to Bcl-2, indicating a matrix-derived cytoskeleton-mediated proapoptotic signaling. Polymerase chain reaction allowed for quantification of messenger RNA expression for Bcl-2. RESULTS: In both bicuspid and tricuspid aneurysms, fibrillar collagens were reduced, whereas fibronectin and tenascin were increased compared with those in normal conditions. These matrix alterations were already evident in bicuspid nonaneurysmal aortas at the convexity, with significant elevation of apoptotic indexes (P = .02 bicuspid vs normal; P = .48 tricuspid vs normal). Apoptotic indexes correlated with aortic dimensions only in tricuspid aortas (P = .01). No significant increase in Ki-67 was found. Higher levels of Bcl-2-modifying factor-Bcl-2 binding were found in bicuspid nonaneurysmal aorta versus tricuspid (P = .03) and normal aortas (P = .01). Bcl-2 messenger RNA expression was reduced in the bicuspid aorta versus normal (P = .08). CONCLUSIONS: Smooth muscle cell apoptosis with bicuspid aortic valve stenosis occurred before overt aortic dilation, mainly at the convexity, where wall stress is expectedly higher. In this setting, a matrix-dependent proapoptotic signaling was evidenced by increased Bcl-2-modifying factor-Bcl-2 binding. Stress-dependent bicuspid aortic valve matrix changes may trigger early apoptosis by inducing cytoskeletal rearrangement.

OBJECTIVE: This study aimed to assess extracellular matrix protein expression patterns at the convexity (right anterolateral wall) and the concavity of the dilated ascending aorta in patients with bicuspid aortic valve disease. METHODS: Aortic wall specimens were retrieved from the convexity and the concavity in 27 bicuspid aortic valve patients (12 with stenosis and 15 with regurgitation) and 6 heart donors (controls). Morphometry, immunohistochemistry, Western blot, and polymerase chain reaction were performed, focusing on matrix proteins involved in vascular remodeling. RESULTS: Type I and III collagens were significantly decreased in bicuspid-associated dilated aortas versus controls (P < .001), particularly at the convexity (P < .05 vs concavity). Expression of messenger RNA for collagens was lower than normal only in the regurgitant subgroup. At immunohistochemistry, proteins whose overproduction has been demonstrated in response to abnormal wall stress, such as tenascin and fibronectin, were more expressed in the convexity than in the concavity, especially in the stenosis subgroup. Tenascin, which is produced by smooth muscle cells in the synthetic phenotype, was nearly undetectable in controls. Fewer smooth muscle cells (stenosis, P = .017; regurgitation, P = .008) and more severe elastic fiber fragmentation (P = .029 and P < .001) were observed in the convexity versus the concavity. CONCLUSIONS: In bicuspid-associated aortic dilations, an asymmetric pattern of matrix protein expression was found that was consistent with the asymmetry in wall-stress distribution reported previously. Differences exist between patients with stenosis and those with regurgitation in terms of protein expression and content in the aortic wall. Further studies could clarify the relations between these findings and the pathogenesis of aortic dilatation in bicuspid aortic valve patients.