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Veronica Papa

Università degli studi di Napoli "Parthenope", Dipartimento di Scienze Motorie e del Benessere, Faculty Member

University of Cassino and Southern Latium, SUSS, Department Member

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Veronica Papa was born in Naples in 1980; she graduated summa cum laude in biochemistry at the University of Naples "Federico II" in 2005 and received her PhD in Human Morphological and Molecular Sciences in Bologna in 2008.
From 2009 to 2018 she served as Assistant Professor of Anatomy at the Department of Social Human and Health Sciences at the University of Cassino.
She is currently Assistant Professor of Anatomy at the Department of Sport Sciences and Wellness, University of Naples “Parthenope”
Her research interests include: anatomy, history of medicine and paleopathology.

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Francesco Maria Galassi

University of Łódz

Flinders University of South Australia

Roberta Ballestriero

Central Saint Martins College of Art and Design, University of the Arts London

San Diego Miramar College

Mauro Vaccarezza

Sultan Qaboos University

Johns Hopkins University

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Papers by Veronica Papa

The teaching of anatomy throughout the centuries: From Herophilus to plastination and beyond

Cultural changes, scientific progress, and new trends in medical education have modified the role... more Cultural changes, scientific progress, and new trends in medical education have modified the role of dissection in the teaching of anatomy in today's medical schools. Dissection is indispensable for a correct and complete knowledge of human anatomy, which can ensure safe as well as efficient clinical practice and the human dissection lab could possibly be the ideal place to cultivate humanistic qualities among future physicians. In this manuscript, we discuss the role of dissection itself, the value of which has been under debate for the last 30 years; furthermore, we attempt to focus on the way in which anatomy knowledge was delivered throughout the centuries, from the ancient times, through the Middles Ages to the present. Finally, we document the rise of plastination as a new trend in anatomy education both in medical and non-medical practice.

The muscles of the athletes to learn surface anatomy - The Influence of classical statues on anatomy teaching

Italian journal of anatomy and embryology, 2019

Gross anatomy classes are still regarded as an integral part of human biomedical education worldw... more Gross anatomy classes are still regarded as an integral part of human biomedical education worldwide. The first documentary evidence of the practice of anatomical dissection for teaching purposes dates back to the 13th century AD, although this practice seems to have originated in Ancient Greece, if not in earlier times. Dissection of the human body is practiced in most anatomy institutions worldwide despite increasing pressure to reduce material and staff costs, regardless the ongoing debate concerning the suitability of body donors for medical education. Moreover, anatomical teaching skills are also evolving and need to be tailored for the different areas of anatomical expertise students have to acquire: therefore, anatomic dissection goes probably beyond the scope of anatomy teaching in some classes such as sports sciences. However, there is no doubt that a practical approach to the study and teaching of anatomy is surely preferable to basic ex cathedra anatomy lectures. Here, we...

Anatomy teaching to Sport Science students

Anatomy has historically been a cornerstone in medical education regardless of nation, racial bac... more Anatomy has historically been a cornerstone in medical education regardless of nation, racial background, or medical school system. By learning gross anatomy, medical students get a first “impression” about the structure of the human body which is the basis for understanding pathologic and clinical problems. Gross anatomy classes are still regarded as an integral part of human biomedical education worldwide. Dissection of the human body is practiced in most anatomy institutions worldwide despite increasing pressure to reduce material and staff costs, regardless the ongoing debate concerning the suitability of body donors for medical education. Moreover, anatomical teaching skills are also evolving and need to be tailored for the different areas of anatomical expertise students have to acquire therefore, anatomic dissection goes probably beyond the scope of anatomy teaching in some classes such as sports sciences. However, there is no doubt that a practical approach to the study and ...

Biochemical and immunohistochemical identification of MMP-7 in human dentin

Journal of Dentistry, 2018

Objectives: Matrix metalloproteinases (MMPs) are dentinal endogenous enzymes claimed to have a vi... more Objectives: Matrix metalloproteinases (MMPs) are dentinal endogenous enzymes claimed to have a vital role in dentin organic matrix breakdown. The aim of the study was to investigate presence, localization and distribution of MMP-7 in sound human dentin. Methods: Dentin was powdered, demineralized and dissolved in isoelectric focusing buffer. Resolved proteins were transferred to nitrocellulose membranes for western blotting (WB) analyses. For the zymographic analysis, aliquots of dentin protein were electrophoresed in 12% sodium dodecyl sulfate-polyacrylamide gel electrophoresis containing fluorescently labeled gelatin. Further, the concentrations of dentinal MMPs were measured using Fluorescent Microsphere Immunoassay with a human MMP-MAP multiplex kit. Pre-and post-embedding immunolabeling technique was used to investigate the localization and distribution of MMP-7 in dentin. Dentin was cryo-fractured, the fragments partially decalcified and labeled with a primary monoclonal anti-MMP-7 and a secondary antibody conjugated with gold nanoparticles. MMP-7 labelings were identified in the demineralized dentin matrix as highly electron-dense dispersed gold particles. Results: WB and zymographic analysis of extracted dentin proteins showed presence of MMP-7 (∼20-28 KDa). Further, MMP-7 was found in the supernatants of the incubated dentin beams using Fluorescent Microsphere Immunoassay. FEI-SEM and TEM analyses established MMP-7 as an intrinsic constituent of the human dentin organic matrix. Conclusion: This study demonstrated that MMP-7 is an endogenous component of the human dentin fibrillar network. Clinical significance: It is pivotal to understand the underlying processes behind dentin matrix remodeling and degradation in order to develop the most optimal clinical protocols and ensure the longevity of dental restorations.

Nuclear expression of diacylglycerol kinases: possible involvement in DNA replication

European Journal of Histochemistry, 2006

Mineral fiber-mediated activation of phosphoinositide-specific phospholipase C in human bronchoalveolar carcinoma-derived alveolar epithelial A549 cells

International Journal of Oncology, 2009

Given the role of phosphoinositide-specific phospholipase C (PLC) isozymes in the control of cell... more Given the role of phosphoinositide-specific phospholipase C (PLC) isozymes in the control of cell growth and differentiation we were prompted to analyze the expression of some of these PLC in human bronchoalveolar carcinomaderived alveolar epithelial A549 cells. The effects of several fluoro-edenite fibers were compared with those of tremolite, a member of the calcic amphibole group of asbestos that originates from Calabria (Italy), and crocidolite, that, due to its high toxicity, is one of the most studied asbestos amphiboles. Our data show an increased expression of both PLC ß1 and PLC Á1 in A549 cells treated with asbestos-like fibers, hinting at a role of PLC signalling in those cancerous cells.

Erucylphosphohomocholine, the first intravenously applicable alkylphosphocholine, is cytotoxic to acute myelogenous leukemia cells through JNK- and PP2A-dependent mechanisms

Leukemia, 2010

Alkylphospholipids and alkylphosphocholines (APCs) are promising antitumor agents, which target t... more Alkylphospholipids and alkylphosphocholines (APCs) are promising antitumor agents, which target the plasma membrane and affect multiple signal transduction networks. We investigated the therapeutic potential of erucylphosphohomocholine (ErPC3), the first intravenously applicable APC, in human acute myelogenous leukemia (AML) cells. ErPC3 was tested on AML cell lines, as well as AML primary cells. At short (6-12 h) incubation times, the drug blocked cells in G2/M phase of the cell cycle, whereas, at longer incubation times, it decreased survival and induced cell death by apoptosis. ErPC3 caused JNK 1/2 activation as well as ERK 1/2 dephosphorylation. Pharmacological inhibition of caspase-3 or a JNK 1/2 inhibitor peptide markedly reduced ErPC3 cytotoxicity. Protein phosphatase 2A downregulation by siRNA opposed ERK 1/2 dephosphorylation and blunted the cytotoxic effect of ErPC3. ErPC3 was cytotoxic to AML primary cells and reduced the clonogenic activity of CD34 þ leukemic cells. ErPC3 induced a significant apoptosis in the compartment (CD34 þ CD38 Low/Neg CD123 þ) enriched in putative leukemia-initiating cells. This conclusion was supported by ErPC3 cytotoxicity on AML blasts showing high aldehyde dehydrogenase activity and on the side population of AML cell lines and blasts. These findings indicate that ErPC3 might be a promising therapeutic agent for the treatment of AML patients.

Proapoptotic activity and chemosensitizing effect of the novel Akt inhibitor perifosine in acute myelogenous leukemia cells

Leukemia, 2007

The serine/threonine kinase Akt, a downstream effector of phosphatidylinositol 3-kinase (PI3K), i... more The serine/threonine kinase Akt, a downstream effector of phosphatidylinositol 3-kinase (PI3K), is known to play an important role in antiapoptotic signaling and has been implicated in the aggressiveness of a number of different human cancers including acute myelogenous leukemia (AML). We have investigated the therapeutic potential of the novel Akt inhibitor, perifosine, on human AML cells. Perifosine is a synthetic alkylphospholipid, a new class of antitumor agents, which target plasma membrane and inhibit signal transduction networks. Perifosine was tested on THP-1 and MV 4-11 cell lines, as well as primary leukemia cells. Perifosine treatment induced cell death by apoptosis in AML cell lines. Perifosine caused Akt and ERK 1/2 dephosphorylation as well as caspase activation. In THP-1 cells, the proapoptotic effect of perifosine was partly dependent on the Fas/FasL system and c-jun-N-kinase activation. In MV 4-11 cells, perifosine downregulated phosphorylated Akt, but not phosphorylated FLT3. Moreover, perifosine reduced the clonogenic activity of AML, but not normal, CD34 þ cells, and markedly increased blast cell sensitivity to etoposide. Our findings indicate that perifosine, either alone or in combination with existing drugs, might be a promising therapeutic agent for the treatment of those AML cases characterized by upregulation of the PI3K-Akt survival pathway.

Multidrug resistance-associated protein 1 expression is under the control of the phosphoinositide 3 kinase/Akt signal transduction network in human acute myelogenous leukemia blasts

Leukemia, 2007

A high incidence of relapses following induction chemotherapy is a major hindrance to patient sur... more A high incidence of relapses following induction chemotherapy is a major hindrance to patient survival in acute myelogenous leukemia (AML). There is strong evidence that activation of the phosphoinositide 3 kinase (PI3K)/Akt signaling network plays a significant role in rendering AML blasts drug resistant. An important mechanism underlying drug resistance is represented by overexpression of membrane drug transporters such as multidrug resistance-associated protein 1 (MRP1) or 170-kDa P-glycoprotein (P-gp). Here, we present evidence that MRP1, but not P-gp, expression is under the control of the PI3K/Akt axis in AML blasts. We observed a highly significant correlation between levels of phosphorylated Akt and MRP1 expression in AML cells. Furthermore, incubation of AML blasts with wortmannin, a PI3K pharmacological inhibitor, resulted in lower levels of phosphorylated Akt, downregulated MRP1 expression, and decreased Rhodamine 123 extrusion in an in vitro functional dye efflux assay. We also demonstrate that wortmannin-dependent PI3K/Akt inhibition upregulated p53 protein levels in most AML cases, and this correlated with diminished MRP1 expression and enhanced phosphorylation of murine double minute 2 (MDM2). Taken together, these data suggest that PI3K/Akt activation may lead to the development of chemoresistance in AML blasts through a mechanism involving a p53-dependent suppression of MRP1 expression.

MMP-2 assay within the hybrid layer created by a two-step etch-and-rinse adhesive: Biochemical and immunohistochemical analysis

Journal of Dentistry, 2011

Objective: Degradation of hybrid layers (HLs) within resin-infiltrated dentine results from multi... more Objective: Degradation of hybrid layers (HLs) within resin-infiltrated dentine results from multiple degradation factors, including collagenolytic activity of specific matrix metalloproteinases (MMPs). Inhibition of host-derived MMPs may, therefore, slow the degradation of HL. The null hypothesis tested is that the presence of MMP-2 is similar regardless of chlorhexidine (CHX) pre-treatment or the use of an adhesive. Methods: Powdered dentine prepared from extracted human teeth was divided into 4 groups: (G1) mineralised powder (control group); (G2) dentine powder treated with 1% phosphoric acid for 1 min; (G3) 1% phosphoric acid-etched dentine treated with Adper Scotchbond 1 XT (SB1XT; 3M ESPE); (G4) 1% phosphoric acid-etched dentine treated with 0.2% CHX followed by SB1XT. The concentration of detectable pro-MMP-2 and MMP-2 was assayed using a colorimetric assay system (QuantiSir). In addition, the presence of MMP-2 in the HL was assessed in 1 year-aged adhesive-dentine interfaces using an immunohistochemical approach under FEI-SEM/TEM. Results: In dentine powder treated with 1% phosphoric acid (G2), MMP-2 level decreased compared to controls (G1); the application of SB1XT (G3) resulted in an increase of MMP-2, whilst 0.2% CHX before SB1XT application (G4), reduced MMP-2. The FEI-SEM/TEM analysis revealed MMP-2 distribution within the HL of aged interfaces showing increase MMP-2 patterns in the control group and minor labelling in the CHX-pretreated specimens.

MMP Activity in the Hybrid Layer Detected with in situ Zymography

Journal of Dental Research, 2012

Dentinal proteases are believed to play an important role in the degradation of hybrid layers (HL... more Dentinal proteases are believed to play an important role in the degradation of hybrid layers (HL). This study investigated the HL gelatinolytic activity by in situ zymography and functional enzyme activity assay. The hypotheses were that HLs created by an etch-and-rinse adhesive exhibit active gelatinolytic activity, and MMP-2 and -9 activities in dentin increase during adhesive procedures. Etched-dentin specimens were bonded with Adper Scotchbond 1XT and restored with composite. Adhesive/dentin interface slices were placed on microscope slides, covered with fluorescein-conjugated gelatin, and observed with a multi-photon confocal microscope after 24 hrs. Human dentin powder aliquots were prepared and assigned to the following treatments: A, untreated; B, etched with 10% phosphoric acid; or C, etched with 10% phosphoric acid and mixed with Scotchbond 1XT. The MMP-2 and -9 activities of extracts of dentin powder were measured with functional enzyme assays. Intense and continuous enz...

Effect of bonding on MMP-2 in human dentin

Dental Materials, 2010

e142 d e n t a l m a t e r i a l s 2 6 (2 0 1 0) e125-e157 there was no significant effect on the... more

MMP-2 and -9 activity induced by etch-and-rinse adhesives

Dental Materials, 2011

lyzed with two-way ANOVA (factors: adhesive type and time) and Tukey' s post hoc test. Results: M... more lyzed with two-way ANOVA (factors: adhesive type and time) and Tukey' s post hoc test. Results: Means and standard deviations of microtensile bond strength are reported in the table. TBS time zero (MPa) TBS 6 months (MPa) Optibond XTR 40.6 (13.0) bc 37.2 (12.1) b Bond Force 33.8 (12.5) b 23.3 (9.6) a Adper Easy Bond 43.8 (15.6) c 36.6 (9.6) b Clearfil SE Bond 37.7/12.4 b 34.5 (13.0) b Different superscript letters identify statistical differences (p < 0.05). Conclusions: The tested hypothesis was partially rejected because the bond strengths of Adper Easy Bond and Bond Force were significantly reduced (p < 0.05) after 6-month water storage in artificial saliva, while the bond strengths of Optibond XTR and Clearfil SE were not affected after aging (p < 0.05). Optibond XTR, Adper Easy Bond and Clearfil SE showed higher bond strength values compared to Bond Force after 6-month water storage in artificial saliva (p < 0.05). Further in vivo studies are needed to clarify the clinical performance of these self-etch adhesives.

Synergistic Proapoptotic Activity of Recombinant TRAIL Plus the Akt Inhibitor Perifosine in Acute Myelogenous Leukemia Cells

Cancer Research, 2008

To potentiate the response of acute myelogenous leukemia (AML) cells to tumor necrosis factor–rel... more To potentiate the response of acute myelogenous leukemia (AML) cells to tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) cytotoxicity, we have examined the efficacy of a combination with perifosine, a novel phosphatidylinositol-3-kinase (PI3K)/Akt signaling inhibitor. The rationale for using such a combination is that perifosine was recently described to increase TRAIL-R2 receptor expression and decrease the cellular FLICE-inhibitory protein (cFLIP) in human lung cancer cell lines. Perifosine and TRAIL both induced cell death by apoptosis in the THP-1 AML cell line, which is characterized by constitutive PI3K/Akt activation, but lacks functional p53. Perifosine, at concentrations below IC50, dephosphorylated Akt and increased TRAIL-R2 levels, as shown by Western blot, reverse transcription-PCR, and flow cytometric analysis. Perifosine also decreased the long isoform of cFLIP (cFLIP-L) and the X-linked inhibitor of apoptosis protein (XIAP) expression. Perifosine and TR...

Immunohistochemical Identification of Decorin and Biglycan in Human Dentin: A Correlative Field Emission Scanning Electron Microscopy/Transmission Electron Microscopy Study

Calcified Tissue International, 2007

Decorin and biglycan, two small leucine-rich proteoglycans, have been proposed to play important ... more Decorin and biglycan, two small leucine-rich proteoglycans, have been proposed to play important roles in matrix-mediated formation of mineralized tissues, and their three-dimensional arrangement in human dentin is still not completely understood. The aim of this study was to immunohistochemically analyze the distribution of decorin and biglycan in human predentin/dentin organic matrix under a high-resolution field emission in-lens scanning electron microscope (FEI-SEM) and a transmission electron microscope (TEM). Tooth dentin specimens were submitted to either a preembedding or a postembedding immunolabeling technique using primary antibodies antidecorin and antibiglycan and gold-conjugated secondary antibodies. Correlative FEI-SEM/TEM observations showed that the two antibodies yielded a similar labeling pattern over the processes of odontoblasts and the predentin. Decorin and biglycan were mainly associated with the collagen fibers within the predentin layer, revealing a moderate immunoreaction that was significantly higher compared to the one observed on dentin. Thus, a generally weak labeling for decorin was found in dentin, which, however, was significantly higher on odontoblast processes within dentinal tubules than in intertubular dentin. On the other hand, biglycan immunolocalization on dentin revealed few gold particles rather uniformly distributed, without showing significant differences between tubular and intertubular regions. In conclusion, this study reveals distinct distribution patterns of decorin and biglycan and their relation with collagen. Decorin's and biglycan's precise roles within prematrix and mineralized matrix in human teeth should be further clarified.

Spina Bifida Sacralis Occulta from Ancient Greek Sicily (Pozzanghera Necropolis, Leontinoi, 6th–4th Century BC): Anatomical, Anthropological and Ethnomedical Considerations on the Insular Presentation of this Congenital Anomaly

Anthropological Review

In this article a case of spina bifida sacralis occulta (SBSO) from the Pozzanghera necropolis of... more In this article a case of spina bifida sacralis occulta (SBSO) from the Pozzanghera necropolis of the ancient Greek colony of Leontinoi (Sicily) and archaeologically dated to the 6th–4th century BC is morphologically analysed and discussed. An ethnomedical excursus on the knowledge and impact of this condition in Sicilian history is offered. Although SBO is one of the most frequent congenital anomalies in the global palaeopathological record, a comprehensive literature search did not yield results for the history of Sicily before Christ, hence this case enriches existing knowledge on the historical presentation of this vertebral congenital anomaly in this region.

Teaching Anatomy in the XXI Century: New Aspects and Pitfalls

Anatomy has historically been a cornerstone in medical education regardless of nation, racial bac... more Anatomy has historically been a cornerstone in medical education regardless of nation, racial background, or medical school system. By learning gross anatomy, medical students get a first "impression" about the structure of the human body which is the basis for understanding pathologic and clinical problems. Although the importance of teaching anatomy to both undergraduate and postgraduate students remains undisputed, there is currently a relevant debate concerning methods of anatomy teaching. In the past century, dissection and lectures were its sole pedagogy worldwide. Recently, the time allocated for anatomy teaching was dramatically reduced to such an extent that some suggest that it has fallen below an adequate standard. Traditional anatomy education based on topographical structural anatomy taught in lectures and gross dissection classes has been replaced by a multiple range of study modules, including problem-based learning, plastic models or computer-assisted learn...

Identification of MMP-8 in human sound dentin

Italian journal of anatomy and embryology, 2010

Objective Matrix metalloproteinases (MMPs), a class of Ca/Zn-dependent endopeptidases, are secret... more Objective Matrix metalloproteinases (MMPs), a class of Ca/Zn-dependent endopeptidases, are secreted by odontoblasts as proenzymes that remain trapped within the mineralized dentin matrix. Activation of these proenzymes is a critical step that leads to dentin extracellular matrix breakdown. The study aimed to assess presence, localization and distribution of MMP-8 in human sound dentin by biochemical and immunohistochemical assays. Methods The presence of MMP-8 in human sound dentin was assayed using a colorimetric assay system that allows direct measuring of MMP-8 levels (QuantisirTM, Epigentek, USA): powdered dentin prepared from extracted human teeth was prepared and 1) partially demineralized with 1% H3PO4 for 10 min or 2) untreated (control). To further detect the localization and distribution of MMP-8 within the dentin organic matrix, dentin cryo-fractured fragments were obtained from human sound teeth, partially decalcified in 0.5 M EDTA pH 7.4 for 30min and submitted to a pre...

Intranuclear 3'-phosphoinositide metabolism and apoptosis protection in PC12 cells

Acta bio-medica : Atenei Parmensis, 2007

Lipid second messengers, particularly those derived from the polyphosphoinositide metabolism, pla... more Lipid second messengers, particularly those derived from the polyphosphoinositide metabolism, play a pivotal role in multiple cell signaling networks. Phosphoinositide 3-kinase (PI3K) generates specific 3'-phosphorylated inositol lipids that have been implicated in a multitude of cell functions. One of the best characterized targets of PI3K lipid products is the serine/threonine protein kinase Akt (protein kinase B). Recent findings have implicated the PI3K/Akt pathway in cancer progression because it stimulates cell proliferation and suppresses apoptosis. Evidence accumulated over the past 15 years has highlighted the presence of an autonomous nuclear inositol lipid cycle, and strongly suggests that lipid molecules are important components of signaling networks operating within the nucleus. PI3K, its lipid products, and Akt have also been identified at the nuclear level. In this review, we shall summarize the most updated findings about these molecules in relationship with supp...

Arts-Based Approach in Teaching Gross Anatomy to Sports Science Undergraduated Student: A Pilot Study

The teaching of anatomy throughout the centuries: From Herophilus to plastination and beyond

Cultural changes, scientific progress, and new trends in medical education have modified the role... more Cultural changes, scientific progress, and new trends in medical education have modified the role of dissection in the teaching of anatomy in today's medical schools. Dissection is indispensable for a correct and complete knowledge of human anatomy, which can ensure safe as well as efficient clinical practice and the human dissection lab could possibly be the ideal place to cultivate humanistic qualities among future physicians. In this manuscript, we discuss the role of dissection itself, the value of which has been under debate for the last 30 years; furthermore, we attempt to focus on the way in which anatomy knowledge was delivered throughout the centuries, from the ancient times, through the Middles Ages to the present. Finally, we document the rise of plastination as a new trend in anatomy education both in medical and non-medical practice.

The muscles of the athletes to learn surface anatomy - The Influence of classical statues on anatomy teaching

Italian journal of anatomy and embryology, 2019

Gross anatomy classes are still regarded as an integral part of human biomedical education worldw... more Gross anatomy classes are still regarded as an integral part of human biomedical education worldwide. The first documentary evidence of the practice of anatomical dissection for teaching purposes dates back to the 13th century AD, although this practice seems to have originated in Ancient Greece, if not in earlier times. Dissection of the human body is practiced in most anatomy institutions worldwide despite increasing pressure to reduce material and staff costs, regardless the ongoing debate concerning the suitability of body donors for medical education. Moreover, anatomical teaching skills are also evolving and need to be tailored for the different areas of anatomical expertise students have to acquire: therefore, anatomic dissection goes probably beyond the scope of anatomy teaching in some classes such as sports sciences. However, there is no doubt that a practical approach to the study and teaching of anatomy is surely preferable to basic ex cathedra anatomy lectures. Here, we...

Anatomy teaching to Sport Science students

Anatomy has historically been a cornerstone in medical education regardless of nation, racial bac... more Anatomy has historically been a cornerstone in medical education regardless of nation, racial background, or medical school system. By learning gross anatomy, medical students get a first “impression” about the structure of the human body which is the basis for understanding pathologic and clinical problems. Gross anatomy classes are still regarded as an integral part of human biomedical education worldwide. Dissection of the human body is practiced in most anatomy institutions worldwide despite increasing pressure to reduce material and staff costs, regardless the ongoing debate concerning the suitability of body donors for medical education. Moreover, anatomical teaching skills are also evolving and need to be tailored for the different areas of anatomical expertise students have to acquire therefore, anatomic dissection goes probably beyond the scope of anatomy teaching in some classes such as sports sciences. However, there is no doubt that a practical approach to the study and ...

Biochemical and immunohistochemical identification of MMP-7 in human dentin

Journal of Dentistry, 2018

Objectives: Matrix metalloproteinases (MMPs) are dentinal endogenous enzymes claimed to have a vi... more Objectives: Matrix metalloproteinases (MMPs) are dentinal endogenous enzymes claimed to have a vital role in dentin organic matrix breakdown. The aim of the study was to investigate presence, localization and distribution of MMP-7 in sound human dentin. Methods: Dentin was powdered, demineralized and dissolved in isoelectric focusing buffer. Resolved proteins were transferred to nitrocellulose membranes for western blotting (WB) analyses. For the zymographic analysis, aliquots of dentin protein were electrophoresed in 12% sodium dodecyl sulfate-polyacrylamide gel electrophoresis containing fluorescently labeled gelatin. Further, the concentrations of dentinal MMPs were measured using Fluorescent Microsphere Immunoassay with a human MMP-MAP multiplex kit. Pre-and post-embedding immunolabeling technique was used to investigate the localization and distribution of MMP-7 in dentin. Dentin was cryo-fractured, the fragments partially decalcified and labeled with a primary monoclonal anti-MMP-7 and a secondary antibody conjugated with gold nanoparticles. MMP-7 labelings were identified in the demineralized dentin matrix as highly electron-dense dispersed gold particles. Results: WB and zymographic analysis of extracted dentin proteins showed presence of MMP-7 (∼20-28 KDa). Further, MMP-7 was found in the supernatants of the incubated dentin beams using Fluorescent Microsphere Immunoassay. FEI-SEM and TEM analyses established MMP-7 as an intrinsic constituent of the human dentin organic matrix. Conclusion: This study demonstrated that MMP-7 is an endogenous component of the human dentin fibrillar network. Clinical significance: It is pivotal to understand the underlying processes behind dentin matrix remodeling and degradation in order to develop the most optimal clinical protocols and ensure the longevity of dental restorations.

Nuclear expression of diacylglycerol kinases: possible involvement in DNA replication

European Journal of Histochemistry, 2006

Mineral fiber-mediated activation of phosphoinositide-specific phospholipase C in human bronchoalveolar carcinoma-derived alveolar epithelial A549 cells

International Journal of Oncology, 2009

Given the role of phosphoinositide-specific phospholipase C (PLC) isozymes in the control of cell... more Given the role of phosphoinositide-specific phospholipase C (PLC) isozymes in the control of cell growth and differentiation we were prompted to analyze the expression of some of these PLC in human bronchoalveolar carcinomaderived alveolar epithelial A549 cells. The effects of several fluoro-edenite fibers were compared with those of tremolite, a member of the calcic amphibole group of asbestos that originates from Calabria (Italy), and crocidolite, that, due to its high toxicity, is one of the most studied asbestos amphiboles. Our data show an increased expression of both PLC ß1 and PLC Á1 in A549 cells treated with asbestos-like fibers, hinting at a role of PLC signalling in those cancerous cells.

Erucylphosphohomocholine, the first intravenously applicable alkylphosphocholine, is cytotoxic to acute myelogenous leukemia cells through JNK- and PP2A-dependent mechanisms

Leukemia, 2010

Alkylphospholipids and alkylphosphocholines (APCs) are promising antitumor agents, which target t... more Alkylphospholipids and alkylphosphocholines (APCs) are promising antitumor agents, which target the plasma membrane and affect multiple signal transduction networks. We investigated the therapeutic potential of erucylphosphohomocholine (ErPC3), the first intravenously applicable APC, in human acute myelogenous leukemia (AML) cells. ErPC3 was tested on AML cell lines, as well as AML primary cells. At short (6-12 h) incubation times, the drug blocked cells in G2/M phase of the cell cycle, whereas, at longer incubation times, it decreased survival and induced cell death by apoptosis. ErPC3 caused JNK 1/2 activation as well as ERK 1/2 dephosphorylation. Pharmacological inhibition of caspase-3 or a JNK 1/2 inhibitor peptide markedly reduced ErPC3 cytotoxicity. Protein phosphatase 2A downregulation by siRNA opposed ERK 1/2 dephosphorylation and blunted the cytotoxic effect of ErPC3. ErPC3 was cytotoxic to AML primary cells and reduced the clonogenic activity of CD34 þ leukemic cells. ErPC3 induced a significant apoptosis in the compartment (CD34 þ CD38 Low/Neg CD123 þ) enriched in putative leukemia-initiating cells. This conclusion was supported by ErPC3 cytotoxicity on AML blasts showing high aldehyde dehydrogenase activity and on the side population of AML cell lines and blasts. These findings indicate that ErPC3 might be a promising therapeutic agent for the treatment of AML patients.

Proapoptotic activity and chemosensitizing effect of the novel Akt inhibitor perifosine in acute myelogenous leukemia cells

Leukemia, 2007

The serine/threonine kinase Akt, a downstream effector of phosphatidylinositol 3-kinase (PI3K), i... more The serine/threonine kinase Akt, a downstream effector of phosphatidylinositol 3-kinase (PI3K), is known to play an important role in antiapoptotic signaling and has been implicated in the aggressiveness of a number of different human cancers including acute myelogenous leukemia (AML). We have investigated the therapeutic potential of the novel Akt inhibitor, perifosine, on human AML cells. Perifosine is a synthetic alkylphospholipid, a new class of antitumor agents, which target plasma membrane and inhibit signal transduction networks. Perifosine was tested on THP-1 and MV 4-11 cell lines, as well as primary leukemia cells. Perifosine treatment induced cell death by apoptosis in AML cell lines. Perifosine caused Akt and ERK 1/2 dephosphorylation as well as caspase activation. In THP-1 cells, the proapoptotic effect of perifosine was partly dependent on the Fas/FasL system and c-jun-N-kinase activation. In MV 4-11 cells, perifosine downregulated phosphorylated Akt, but not phosphorylated FLT3. Moreover, perifosine reduced the clonogenic activity of AML, but not normal, CD34 þ cells, and markedly increased blast cell sensitivity to etoposide. Our findings indicate that perifosine, either alone or in combination with existing drugs, might be a promising therapeutic agent for the treatment of those AML cases characterized by upregulation of the PI3K-Akt survival pathway.

Multidrug resistance-associated protein 1 expression is under the control of the phosphoinositide 3 kinase/Akt signal transduction network in human acute myelogenous leukemia blasts

Leukemia, 2007

A high incidence of relapses following induction chemotherapy is a major hindrance to patient sur... more A high incidence of relapses following induction chemotherapy is a major hindrance to patient survival in acute myelogenous leukemia (AML). There is strong evidence that activation of the phosphoinositide 3 kinase (PI3K)/Akt signaling network plays a significant role in rendering AML blasts drug resistant. An important mechanism underlying drug resistance is represented by overexpression of membrane drug transporters such as multidrug resistance-associated protein 1 (MRP1) or 170-kDa P-glycoprotein (P-gp). Here, we present evidence that MRP1, but not P-gp, expression is under the control of the PI3K/Akt axis in AML blasts. We observed a highly significant correlation between levels of phosphorylated Akt and MRP1 expression in AML cells. Furthermore, incubation of AML blasts with wortmannin, a PI3K pharmacological inhibitor, resulted in lower levels of phosphorylated Akt, downregulated MRP1 expression, and decreased Rhodamine 123 extrusion in an in vitro functional dye efflux assay. We also demonstrate that wortmannin-dependent PI3K/Akt inhibition upregulated p53 protein levels in most AML cases, and this correlated with diminished MRP1 expression and enhanced phosphorylation of murine double minute 2 (MDM2). Taken together, these data suggest that PI3K/Akt activation may lead to the development of chemoresistance in AML blasts through a mechanism involving a p53-dependent suppression of MRP1 expression.

MMP-2 assay within the hybrid layer created by a two-step etch-and-rinse adhesive: Biochemical and immunohistochemical analysis

Journal of Dentistry, 2011

Objective: Degradation of hybrid layers (HLs) within resin-infiltrated dentine results from multi... more Objective: Degradation of hybrid layers (HLs) within resin-infiltrated dentine results from multiple degradation factors, including collagenolytic activity of specific matrix metalloproteinases (MMPs). Inhibition of host-derived MMPs may, therefore, slow the degradation of HL. The null hypothesis tested is that the presence of MMP-2 is similar regardless of chlorhexidine (CHX) pre-treatment or the use of an adhesive. Methods: Powdered dentine prepared from extracted human teeth was divided into 4 groups: (G1) mineralised powder (control group); (G2) dentine powder treated with 1% phosphoric acid for 1 min; (G3) 1% phosphoric acid-etched dentine treated with Adper Scotchbond 1 XT (SB1XT; 3M ESPE); (G4) 1% phosphoric acid-etched dentine treated with 0.2% CHX followed by SB1XT. The concentration of detectable pro-MMP-2 and MMP-2 was assayed using a colorimetric assay system (QuantiSir). In addition, the presence of MMP-2 in the HL was assessed in 1 year-aged adhesive-dentine interfaces using an immunohistochemical approach under FEI-SEM/TEM. Results: In dentine powder treated with 1% phosphoric acid (G2), MMP-2 level decreased compared to controls (G1); the application of SB1XT (G3) resulted in an increase of MMP-2, whilst 0.2% CHX before SB1XT application (G4), reduced MMP-2. The FEI-SEM/TEM analysis revealed MMP-2 distribution within the HL of aged interfaces showing increase MMP-2 patterns in the control group and minor labelling in the CHX-pretreated specimens.

MMP Activity in the Hybrid Layer Detected with in situ Zymography

Journal of Dental Research, 2012

Dentinal proteases are believed to play an important role in the degradation of hybrid layers (HL... more Dentinal proteases are believed to play an important role in the degradation of hybrid layers (HL). This study investigated the HL gelatinolytic activity by in situ zymography and functional enzyme activity assay. The hypotheses were that HLs created by an etch-and-rinse adhesive exhibit active gelatinolytic activity, and MMP-2 and -9 activities in dentin increase during adhesive procedures. Etched-dentin specimens were bonded with Adper Scotchbond 1XT and restored with composite. Adhesive/dentin interface slices were placed on microscope slides, covered with fluorescein-conjugated gelatin, and observed with a multi-photon confocal microscope after 24 hrs. Human dentin powder aliquots were prepared and assigned to the following treatments: A, untreated; B, etched with 10% phosphoric acid; or C, etched with 10% phosphoric acid and mixed with Scotchbond 1XT. The MMP-2 and -9 activities of extracts of dentin powder were measured with functional enzyme assays. Intense and continuous enz...

Effect of bonding on MMP-2 in human dentin

Dental Materials, 2010

e142 d e n t a l m a t e r i a l s 2 6 (2 0 1 0) e125-e157 there was no significant effect on the... more

MMP-2 and -9 activity induced by etch-and-rinse adhesives

Dental Materials, 2011

lyzed with two-way ANOVA (factors: adhesive type and time) and Tukey' s post hoc test. Results: M... more lyzed with two-way ANOVA (factors: adhesive type and time) and Tukey' s post hoc test. Results: Means and standard deviations of microtensile bond strength are reported in the table. TBS time zero (MPa) TBS 6 months (MPa) Optibond XTR 40.6 (13.0) bc 37.2 (12.1) b Bond Force 33.8 (12.5) b 23.3 (9.6) a Adper Easy Bond 43.8 (15.6) c 36.6 (9.6) b Clearfil SE Bond 37.7/12.4 b 34.5 (13.0) b Different superscript letters identify statistical differences (p < 0.05). Conclusions: The tested hypothesis was partially rejected because the bond strengths of Adper Easy Bond and Bond Force were significantly reduced (p < 0.05) after 6-month water storage in artificial saliva, while the bond strengths of Optibond XTR and Clearfil SE were not affected after aging (p < 0.05). Optibond XTR, Adper Easy Bond and Clearfil SE showed higher bond strength values compared to Bond Force after 6-month water storage in artificial saliva (p < 0.05). Further in vivo studies are needed to clarify the clinical performance of these self-etch adhesives.

Synergistic Proapoptotic Activity of Recombinant TRAIL Plus the Akt Inhibitor Perifosine in Acute Myelogenous Leukemia Cells

Cancer Research, 2008

To potentiate the response of acute myelogenous leukemia (AML) cells to tumor necrosis factor–rel... more To potentiate the response of acute myelogenous leukemia (AML) cells to tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) cytotoxicity, we have examined the efficacy of a combination with perifosine, a novel phosphatidylinositol-3-kinase (PI3K)/Akt signaling inhibitor. The rationale for using such a combination is that perifosine was recently described to increase TRAIL-R2 receptor expression and decrease the cellular FLICE-inhibitory protein (cFLIP) in human lung cancer cell lines. Perifosine and TRAIL both induced cell death by apoptosis in the THP-1 AML cell line, which is characterized by constitutive PI3K/Akt activation, but lacks functional p53. Perifosine, at concentrations below IC50, dephosphorylated Akt and increased TRAIL-R2 levels, as shown by Western blot, reverse transcription-PCR, and flow cytometric analysis. Perifosine also decreased the long isoform of cFLIP (cFLIP-L) and the X-linked inhibitor of apoptosis protein (XIAP) expression. Perifosine and TR...

Immunohistochemical Identification of Decorin and Biglycan in Human Dentin: A Correlative Field Emission Scanning Electron Microscopy/Transmission Electron Microscopy Study

Calcified Tissue International, 2007

Decorin and biglycan, two small leucine-rich proteoglycans, have been proposed to play important ... more Decorin and biglycan, two small leucine-rich proteoglycans, have been proposed to play important roles in matrix-mediated formation of mineralized tissues, and their three-dimensional arrangement in human dentin is still not completely understood. The aim of this study was to immunohistochemically analyze the distribution of decorin and biglycan in human predentin/dentin organic matrix under a high-resolution field emission in-lens scanning electron microscope (FEI-SEM) and a transmission electron microscope (TEM). Tooth dentin specimens were submitted to either a preembedding or a postembedding immunolabeling technique using primary antibodies antidecorin and antibiglycan and gold-conjugated secondary antibodies. Correlative FEI-SEM/TEM observations showed that the two antibodies yielded a similar labeling pattern over the processes of odontoblasts and the predentin. Decorin and biglycan were mainly associated with the collagen fibers within the predentin layer, revealing a moderate immunoreaction that was significantly higher compared to the one observed on dentin. Thus, a generally weak labeling for decorin was found in dentin, which, however, was significantly higher on odontoblast processes within dentinal tubules than in intertubular dentin. On the other hand, biglycan immunolocalization on dentin revealed few gold particles rather uniformly distributed, without showing significant differences between tubular and intertubular regions. In conclusion, this study reveals distinct distribution patterns of decorin and biglycan and their relation with collagen. Decorin's and biglycan's precise roles within prematrix and mineralized matrix in human teeth should be further clarified.

Spina Bifida Sacralis Occulta from Ancient Greek Sicily (Pozzanghera Necropolis, Leontinoi, 6th–4th Century BC): Anatomical, Anthropological and Ethnomedical Considerations on the Insular Presentation of this Congenital Anomaly

Anthropological Review

In this article a case of spina bifida sacralis occulta (SBSO) from the Pozzanghera necropolis of... more In this article a case of spina bifida sacralis occulta (SBSO) from the Pozzanghera necropolis of the ancient Greek colony of Leontinoi (Sicily) and archaeologically dated to the 6th–4th century BC is morphologically analysed and discussed. An ethnomedical excursus on the knowledge and impact of this condition in Sicilian history is offered. Although SBO is one of the most frequent congenital anomalies in the global palaeopathological record, a comprehensive literature search did not yield results for the history of Sicily before Christ, hence this case enriches existing knowledge on the historical presentation of this vertebral congenital anomaly in this region.

Teaching Anatomy in the XXI Century: New Aspects and Pitfalls

Anatomy has historically been a cornerstone in medical education regardless of nation, racial bac... more Anatomy has historically been a cornerstone in medical education regardless of nation, racial background, or medical school system. By learning gross anatomy, medical students get a first "impression" about the structure of the human body which is the basis for understanding pathologic and clinical problems. Although the importance of teaching anatomy to both undergraduate and postgraduate students remains undisputed, there is currently a relevant debate concerning methods of anatomy teaching. In the past century, dissection and lectures were its sole pedagogy worldwide. Recently, the time allocated for anatomy teaching was dramatically reduced to such an extent that some suggest that it has fallen below an adequate standard. Traditional anatomy education based on topographical structural anatomy taught in lectures and gross dissection classes has been replaced by a multiple range of study modules, including problem-based learning, plastic models or computer-assisted learn...

Identification of MMP-8 in human sound dentin

Italian journal of anatomy and embryology, 2010

Objective Matrix metalloproteinases (MMPs), a class of Ca/Zn-dependent endopeptidases, are secret... more Objective Matrix metalloproteinases (MMPs), a class of Ca/Zn-dependent endopeptidases, are secreted by odontoblasts as proenzymes that remain trapped within the mineralized dentin matrix. Activation of these proenzymes is a critical step that leads to dentin extracellular matrix breakdown. The study aimed to assess presence, localization and distribution of MMP-8 in human sound dentin by biochemical and immunohistochemical assays. Methods The presence of MMP-8 in human sound dentin was assayed using a colorimetric assay system that allows direct measuring of MMP-8 levels (QuantisirTM, Epigentek, USA): powdered dentin prepared from extracted human teeth was prepared and 1) partially demineralized with 1% H3PO4 for 10 min or 2) untreated (control). To further detect the localization and distribution of MMP-8 within the dentin organic matrix, dentin cryo-fractured fragments were obtained from human sound teeth, partially decalcified in 0.5 M EDTA pH 7.4 for 30min and submitted to a pre...

Intranuclear 3'-phosphoinositide metabolism and apoptosis protection in PC12 cells

Acta bio-medica : Atenei Parmensis, 2007

Lipid second messengers, particularly those derived from the polyphosphoinositide metabolism, pla... more Lipid second messengers, particularly those derived from the polyphosphoinositide metabolism, play a pivotal role in multiple cell signaling networks. Phosphoinositide 3-kinase (PI3K) generates specific 3'-phosphorylated inositol lipids that have been implicated in a multitude of cell functions. One of the best characterized targets of PI3K lipid products is the serine/threonine protein kinase Akt (protein kinase B). Recent findings have implicated the PI3K/Akt pathway in cancer progression because it stimulates cell proliferation and suppresses apoptosis. Evidence accumulated over the past 15 years has highlighted the presence of an autonomous nuclear inositol lipid cycle, and strongly suggests that lipid molecules are important components of signaling networks operating within the nucleus. PI3K, its lipid products, and Akt have also been identified at the nuclear level. In this review, we shall summarize the most updated findings about these molecules in relationship with supp...

Arts-Based Approach in Teaching Gross Anatomy to Sports Science Undergraduated Student: A Pilot Study

Guerre fra galli e nanismo nell'Antica Roma

by Elena Varotto, Laura Landini, and Veronica Papa

9° Convegno AIAZ - Associazione Italiana Archeozoologia (Ravenna) 28 nov-1 dic 2018, 2018

Sezione tematica: L’archeozoologia e le fonti iconografiche, letterarie e storico- documentali ... more Sezione tematica: L’archeozoologia e le fonti iconografiche, letterarie e storico- documentali

Presso il Museo Archeologico Nazionale di Napoli (MANN) è esposto un mosaico molto suggestivo proveniente dall’antica Pompei noto con il nome di “Nano e Gallo” [Inv: 10003]. La scena raffigura un servo che porge la palma della vittoria ad un gallo risultato trionfante nel ludus gallinarius. Benché il combattimento fra galli fosse alquanto comune nell’antichità, questo mosaico apre scenari assai interessanti per la ricerca archeozoologica e paleopatologica. A quale specie appartiene il gallo? Quale evidenza storica ed archeologica esiste dell’impiego di tale specie nel mondo romano e quale evoluzione della percezione da parte del pubblico generale nei confronti di questo genere di spettacoli di origine greca può essere evidenziata? Inoltre, un’analisi morfologica delle fattezze del servitore permette di identificare un fenotipo acondroplasico per questo antico paziente palesemente affetto da nanismo, il che permette di arricchire le conoscenze sulla presentazione storica di questa malattia nell’antichità, unitamente al dato paleopatologico classico. La ricerca consiste, infine, di un approccio multidisciplinare che si avvale di fonti artistiche, fonti storico-letterarie, evidenze archeologiche, bioarcheologiche ed archeozoologiche.

Diagnosis of Spinal Tuberculosis in a Ptolemaic Dwarf Statue [46th ISHM Congress Lisbona]

by Elena Varotto and Veronica Papa

Authors: Veronica Papa, Francesco Maria Galassi, Elena Varotto

Glasgow Anatomical Society Virtual Summer Meeting 2021: KV55 Akhenaton: Reassessment of the Anthropological Literature and a Novel Facial Reconstruction (2021)

by Dr. Michael E . Habicht and Veronica Papa

Conference: Anatomical Society Meeting 7-9 July 2021, 2021