Publications by authors named "Angelo Favaloro"

40 Publications

Expression of VAChT and 5-HT in Ulcerative colitis dendritic cells.

Acta Histochem 2021 May 30;123(4):151715. Epub 2021 Apr 30.

Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy.

Ulcerative colitis is a chronic inflammatory condition of the gastrointestinal tract that can affect people of worldwide. In contrast with Crohn's disease, that can relate the entire thickness of the bowel wall, the inflammation of ulcerative colitis is limited to the colonic mucosa. Immune cells including activated T cells, plasma cells, mast cells, macrophages, and dendritic cells (DCs) trigger the inflammation. Furthermore, dendritic cells are antigen presenting cells involved in maintaining intestinal immune homeostasis. It has been described an increment of number in DCs colonic mucosa of patients with ulcerative colitis. The immune cells such as antigen-presenting cells can act as autocrine or paracrine modulators. Recent studies showed that dendritic cells synthetized and released classical neurotransmitters as glutamate, dopamine, acetylcholine, and serotonin. Paraformaldehyde-fixed intestinal tissues, obtained from the stricture sites of ten patients with ulcerative colitis were analyzed by immunostaining for Langerin/CD207, serotonin and vesicular acetylcholine transporter. As controls, unaffected (normal) portions of five patients were also investigated. Aim of this study was to characterize for the first time the human gut dendritic cells of ulcerative colitis patients, with Langerin/CD207 that is a c-type lectin expressed by different types of DCs and to colocalize in the same cells the expression of serotonin and vesicular acetylcholine transporter, showing the link between dendritic cells, gut enterochromaffin cells or autonomic nerves in immune activation and generation of intestinal inflammation.
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http://dx.doi.org/10.1016/j.acthis.2021.151715DOI Listing
May 2021

Articular Disc of a Human Temporomandibular Joint: Evaluation through Light Microscopy, Immunofluorescence and Scanning Electron Microscopy.

J Funct Morphol Kinesiol 2021 Feb 25;6(1). Epub 2021 Feb 25.

Department of Clinic and Experimental Medicine, University of Messina, 98100 Messina, Italy.

The extracellular matrix of the articular disc in a temporomandibular joint (TMJ) is composed mainly of collagen I and elastin. The collagen is important for resisting tensile forces, while the elastin is responsible to maintain the shape after deformation. We studied the orientation of collagen and elastin in a normal human temporomandibular joint disc by light microscopy, immunofluorescence and scanning electron microscopy. Our results demonstrated that collagen and elastin run parallel to each other in the intermediate zone with an anteroposterior orientation. From here, the orientation of two fibers groups changes into a disordered arrangement in the transition zone. Numerous elastic fibers cross with the collagen fibers, defining an interwoven knitted arrangement. The evaluation of the disc-condyle relationship shows that the medial margin of the articular disc is inserted directly at the superficial layer of the mandibular condylar cartilage. Therefore, the tensile properties of the TMJ disc are expressed in the directions corresponding to the orientation of the collagen fibers, and the complex orientation of elastin with the collagen determines the maintaining of the shape after the stresses by the joint movements. Moreover, the direct anatomical relationship between the articular disc and the mandibular condyle makes a decisive contribution to the understanding of TMJ movements.
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http://dx.doi.org/10.3390/jfmk6010022DOI Listing
February 2021

Microscopic reconstruction and immunohistochemical analysis of discomalleolar ligament.

Heliyon 2020 Aug 11;6(8):e04651. Epub 2020 Aug 11.

Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Via Consolare Valeria, 1, Messina, Italy.

Discomalleolar ligament represents the vestiges of the primitive lateral pterygoid muscle which penetrates in the caudal end of Meckel's cartilage; during the development of newborn, the petrotympanic fissure close almost completely leaving inside the discomalleolar ligament. After entering in tympanic cavity, some fibers of the discomalleolar ligament insert to walls of cavity, other fibers continue with the lateral margin of the anterior ligament and insert in the neck of malleus; in contrast, other Authors demonstrated that discomalleolar ligament is an independent structure inserted in proximity of the neck of the malleus. Although the discomalleolar ligament can be considered as a structure of clinical importance, it is not described by anatomy textbooks. Moreover, it is likely that important correlations between temporomandibular diseases and otological symptoms exist. We have studied discomalleolar ligament submitting the specimens to the 3D volume rendering technique, light microscopy, reconstructing a wide light microscopic fields to analyze the real connection between retrodiscal connective tissue and middle ear, and immunofluorescence methods in order to analyze the consistence of ligament. We have shown two types of connections between TMJ and ear: first, with external acoustic meatus and, second, with middle ear through discomalleolar ligament. The different insertion represents a strong support in order to demonstrate that the TMJ disorders can determine variations of tension that are transmitted on the tympanic membrane provoking tinnitus in according to clinical features. Then, we propose that it is necessary to mention, also in anatomy textbook, the discomalleolar ligament as ligament distance of TMJ.
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http://dx.doi.org/10.1016/j.heliyon.2020.e04651DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7424222PMC
August 2020

An immunofluorescence study on VEGF and extracellular matrix proteins in human periodontal ligament during tooth movement.

Heliyon 2019 Oct 4;5(10):e02572. Epub 2019 Oct 4.

Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Italy.

The periodontal ligament (PDL) is a highly vascularized connective tissue surrounding the root of a tooth. In particular, the PDL is continuously exposed to mechanical stresses during the phases of mastication, and it provides physical, sensory, and trophic functions. It is known that the application of orthodontic force creates a change in periodontal structures. In fact, these forces generate a pressure on the ligament that closes the vessels. The aim of this study is to observe the modifications of vascular endothelial growth factor (VEGF) in the PDL and extracellular matrix proteins after application of a pre-calibrated and constant orthodontic force at different phases of treatment. We used a 50-g NiTi coiled spring and in vivo samples of PDL of maxillary and mandibular premolars of patients subjected to orthodontic treatment. These teeth were extracted at 1, 7, 14, 21, and 30 days, respectively, by application of force. The extraction of the PDL was effectuated by scarifying the radicular surface on the pressure and tension sides. The mechanical stress induced by the application of force caused an increase in the reactive type of metabolism of extracellular matrix proteins and modulation of neoangiogenesis until restoration.
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http://dx.doi.org/10.1016/j.heliyon.2019.e02572DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6812246PMC
October 2019

Mapping the structural connectivity between the periaqueductal gray and the cerebellum in humans.

Brain Struct Funct 2019 Jul 5;224(6):2153-2165. Epub 2019 Jun 5.

Department of Biomedical, Dental Sciences and Morphological and Functional Images, University of Messina, Messina, Italy.

The periaqueductal gray is a mesencephalic structure involved in modulation of responses to stressful stimuli. Structural connections between the periaqueductal gray and the cerebellum have been described in animals and in a few diffusion tensor imaging studies. Nevertheless, these periaqueductal gray-cerebellum connectivity patterns have yet to be fully investigated in humans. The objective of this study was to qualitatively and quantitatively characterize such pathways using high-resolution, multi-shell data of 100 healthy subjects from the open-access Human Connectome Project repository combined with constrained spherical deconvolution probabilistic tractography. Our analysis revealed robust connectivity density profiles between the periaqueductal gray and cerebellar nuclei, especially with the fastigial nucleus, followed by the interposed and dentate nuclei. High-connectivity densities have been observed between vermal (Vermis IX, Vermis VIIIa, Vermis VIIIb, Vermis VI, Vermis X) and hemispheric cerebellar regions (Lobule IX). Our in vivo study provides for the first time insights on the organization of periaqueductal gray-cerebellar pathways thus opening new perspectives on cognitive, visceral and motor responses to threatening stimuli in humans.
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http://dx.doi.org/10.1007/s00429-019-01893-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6591182PMC
July 2019

Altered Integrins Expression of Patients Affected by Cryptorchidism.

Urol Int 2018 8;101(2):219-223. Epub 2018 Aug 8.

Department of Human Pathology in Adult and Developmental Age Gaetano Barresi, Unit of Paediatric Surgery, University of Messina, Messina, Italy.

Objectives: The study aimed to investigate the expression of the integrin isoforms α7A and β1A, expressed by myogenic precursor cells, and α7B and β1D, expressed by mature muscle cells in the cremaster of patients affected by an undescended testis.

Methods: Fifteen samples of cremaster were obtained from patients undergoing surgery for an undescended testis. Thirty control specimens of cremaster were harvested from patients with congenital hydrocele or inguinal hernia. Immunofluorescent analysis was carried out using anti-α7A, β1A, α7B, and β1D integrin antibodies. Sections were observed using confocal laser scanning microscopy.

Results: As compared with controls, a significant loss of a α7B (p = 0.0355) and β1D (p = 0.0069) integrins and a higher expression of α7A (p = 0.0003) and β1A (p = 0.0150) was detected in the cremaster of patients affected by an undescended testis.

Conclusions: Our data document a critical alteration of the cytoskeleton of cremasteric smooth muscle cells in patients with an undescended testis. This might explain the altered function in smooth muscle cells in cremaster implied during testicular descent. We therefore speculate that the postnatal splicing of α7A to α7B and of β1A to β1D integrins is delayed. This could account for the common clinical scenario of spontaneous descent of the testes in the first months of life.
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http://dx.doi.org/10.1159/000491495DOI Listing
December 2018

Morpho-structural alterations of sub-chondral bone tissue in patients with osteoarthritis: a scanning electron microscopy study.

Ital J Anat Embryol 2015 ;120(1):71-81

Osteoarthritis focuses principally on the degeneration of articular cartilage as a primary cause of the disease. The pathophysiological process of osteoarthritis is characterized by alteration of chondrocytes and the increased bone formation by sub-chondral osteoblasts. Infiltration of macrophages and perivascular T and B lymphocytes is observed, and these infiltrates have been demonstrated in both early and advanced disease. The morphological and phenotypic characteristics of osteocytic cells attached to the normal and the osteoarthritic matrix differ from each other, suggesting that specific signalling pathways arise or are altered between matrix and cells. On this basis, we have examined biopsies of bone obtained by normal femur and by femur of subjects affected by osteoarthritis using techniques of scanning electron microscopy in order to identify the morphostructural alterations that occur in the sub-chondral bone. Our results have shown that the bone tissue of subjects not affected by any disease of bone presents a well-organized structure, while the bone tissue obtained by patients affected by osteoarthritis shows a derangement of tissue itself possibly correlated with altered function of the osteoblasts, that during the pathological process produce a less mineralized extracellular matrix with consequent loss of the normal bone structure. In our opinion, during the osteoarthritic process there would be a defective signalling between bone cells leading to the production of an irregular, amorphous extracellular matrix by osteoblasts, characteristic of the pathological condition.
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February 2016

Dentin Morphology of Root Canal Surface: A Quantitative Evaluation Based on a Scanning Electronic Microscopy Study.

Biomed Res Int 2015 27;2015:164065. Epub 2015 Aug 27.

Department of Human Pathology, University of Messina, Via Consolare Valeria, 98100 Messina, Italy.

Dentin is a vital, hydrated composite tissue with structural components and properties that vary in the different topographic portions of the teeth. These variations have a significant implication for biomechanical teeth properties and for the adhesive systems utilized in conservative dentistry. The aim of this study is to analyse the root canal dentin going from coronal to apical zone to find the ratio between the intertubular dentin area and the surface occupied by dentin tubules varies. Observations were conducted on 30 healthy premolar teeth extracted for orthodontic reasons in patients aged between 10 and 14. A SEM analysis of the data obtained in different canal portions showed that, in the coronal zone, dentinal tubules had a greater diameter (4.32 μm) than the middle zone (3.74 μm) and the apical zone (1.73 μm). The average number of dentinal tubules (in an area of 1 mm(2)) was similar in coronal zone (46,798 ± 10,644) and apical zone (45,192 ± 10,888), while in the middle zone they were lower in number (30,940 ± 7,651). However, intertubular dentin area was bigger going from apical to coronal portion. The differences between the analysed areas must be considered for the choice of the adhesive system.
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http://dx.doi.org/10.1155/2015/164065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4564583PMC
August 2016

Sarcoglycans and gaba(a) receptors in rat central nervous system: an immunohistochemical study.

Ital J Anat Embryol 2015 ;120(2):105-16

Sarcoglycan subcomplex is a transmembrane glycoprotein system which connects extracellular matrix to cytoskeleton. Although this complex has been found in several non-muscular tissues, no data exist about a sarcoglycan subcomplex in brain. Only the presence of ε-sarcoglycan in brain has been described in detail because its mutation determines Myoclonus Dystonia Syndrome. Also ζ-, β- and δ-sarcoglycans have been found in brain but only at mRNA level and their distribution in brain is still unknown. Here, we have searched for the expression of all sarcoglycans in specific brain regions of rat as hippocampus, cerebral and cerebellar cortex. Since a correlation between dystrophin glycoprotein complex and γ-amino butyric acid A (GABA(A)) receptor was demonstrated, we have investigated also a possible colocalization between sarcoglycans and GABA(A) receptor. Results have shown that all sarcoglycans are expressed in neurons of all observed regions; these proteins show a spot-like pattern of fluorescence and are mainly localized at soma level. Moreover, each sarcoglycan colocalizes with GABA(A) receptor. The present study shows, for the first time, the expression of all sarcoglycans in brain; moreover, the prevalent localization of sarcoglycans at post-synaptic level and the colocalization of these glycoproteins with GABA(A) receptor suggests that sarcoglycans play a key role in central nervous system, regulating post-synaptic receptors assembly.
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May 2016

Sarcoglycan complex in human normal and pathological prostatic tissue: an immunohistochemical and RT-PCR study.

Anat Rec (Hoboken) 2014 Feb;297(2):327-36

The sarcoglycan complex is a trans-membrane system playing a key role in mechano-signaling the connection from the cytoskeleton to the extracellular matrix. While b-, d-, and e-sarcoglycans are widely distributed, g- and a-sarcoglycans are expressed exclusively in skeletal and cardiac muscle. Insufficient data are available on the distribution of sarcoglycans in nonmuscular tissue. In the present study, we used immunohistochemical and RT-PCR techniques to study the sarcoglycans also in normal human glandular tissue, a type of tissue never studied in relation to the sarcoglycan complex, with the aim of verifying the real wider distribution of this complex. To understand the role of sarcoglycans, we tested specimens collected from patients affected by benign prostatic hyperplasia and adenocarcinoma. For the first time, our results showed that all sarcoglycans are detectable in normal samples both in epithelial and in myoepithelial cells; in pathological prostate, sarcoglycans appeared severely reduced in number or were absent. These data demonstrated that all sarcoglycans have a wider distribution suggesting a new unknown role for these proteins. The decreased number of sarcoglycans, containing cadherin domain homologs in samples of prostate affected by hyperplasia, and the absence of proteins in prostate biopsies, in cases affected by adenocarcinoma, could be responsible for the loss of adhesion between epithelial cells, which in turn facilitates the progression of benign tumors and the invasive potential of malignant tumors.
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http://dx.doi.org/10.1002/ar.22846DOI Listing
February 2014

Staphylococcal biofilm formation as affected by type acidulant.

APMIS 2014 Jul 10;122(7):648-53. Epub 2013 Dec 10.

Dipartimento di Scienze del Farmaco e dei Prodotti per la Salute, Università di Messina, Messina, Italy.

Staphylococcal growth and biofilm formation in culture medium where pH was lowered with weak organic (acetic and lactic) or strong inorganic (hydrochloric) acids were studied. The effects were evaluated by biomass measurements, cell-surface hydrophobicity, scanning electron microscopy (SEM), and confocal laser scanning microscopy (CLSM). The results demonstrated that the inhibition was related to type of acidulant and pH value. At pH 5.0, the antibacterial effect was more pronounced in the presence of acetic acid (58-60% growth reduction) compared with that in the presence of lactic (7-16% growth reduction) and hydrochloric acids (23-24% reduction). The biofilm biomass of Staphylococcus aureus and Staphylococcus epidermidis was reduced by 92, 85, 63, and 93, 87, 81% after exposition to acetic, lactic, and hydrochloric acids, respectively. Increasing the pH from 5.0 to 6.0 resulted in a noticeable reduction in the effectiveness of acids. A minor cells hydrophobic character was also documented. The SEM and CLSM revealed a poorly structured and thinner biofilm compared with the dense and multilayered control. Acidic environment could have important implications for food-processing system to prevent bacterial colonization and control biofilm formation. The findings of this study lead to consider the rational use of the type of acid to achieve acidic environments.
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http://dx.doi.org/10.1111/apm.12210DOI Listing
July 2014

Sarcoglycans and integrins in bisphosphonate treatment: immunohistochemical and scanning electron microscopy study.

Oncol Rep 2013 Dec 1;30(6):2639-46. Epub 2013 Oct 1.

Department of Experimental Medical, Surgical and Odontostomatological Sciences, University of Messina, Messina, Italy.

Osteonecrosis of the jaw is an adverse outcome associated with bisphosphonate treatment. Bisphosphonates are used in conjunction with antineoplastic chemotherapy for the treatment of hypercalcaemia associated with malignancy, lytic bone metastasis and multiple myeloma. However, it is not known if the osteonecrosis of the jaw lesion originates in the bone or whether it initiates in the gingival epithelium. Two bisphosphonates are commonly used in cancer treatment. One of these is pamidronate disodium, a second-generation bisphosphonate that differs from the first-generation drug because it inhibits bone resorption at a dose that does not affect bone mineralization. The other widely used BP, zoledronate, is a third-generation drug that is the most potent bisphosphonate in clinical use, showing strong anti-osteoclastic activity, similar to pamidronate. The aim of the present study was to evaluate the modifications of human oral mucosa and underlying bone in patients after treatment with these nitrogen-containing bisphosphonates for 24 and 36 months. We analyzed the structural damage of the oral mucosa and damage of the perilesional mandibular bone observing possible correlations from them. Our results allow to express two hypotheses about the mechanism responsible for these results relating to mandible matrix necrosis; first, an increased skeletal microdamage associated with turnover suppression occurred early in treatment and progress with longer treatment duration, second, opening damage in osteonecrosis of the jaw modifies structural morphology of gingival epithelium.
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http://dx.doi.org/10.3892/or.2013.2766DOI Listing
December 2013

The arterial blood supply of the temporomandibular joint: an anatomical study and clinical implications.

Imaging Sci Dent 2013 Mar 11;43(1):37-44. Epub 2013 Mar 11.

Department of Surgical and Oncological Disciplines, University of Palermo, Palermo, Italy.

Purpose: The aim of this study was to analyze three-dimensional images of the arterial supply to the temporomandibular joint.

Materials And Methods: Ten patients (five men and five women, mean age 36 years) without signs or symptoms of temporomandibular disorders, who underwent contrast-enhanced computed tomographic (CT) scanning with intravenous contrast, were studied. The direct volume rendering technique of CT images was used, and a data set of images to visualize the vasculature of the human temporomandibular joint in three dimensions was created. After elaboration of the data through post-processing, the arterial supply of the temporomandibular joint was studied.

Results: The analysis revealed the superficial temporal artery, the anterior tympanic artery, the deep temporal artery, the auricular posterior artery, the transverse facial artery, the middle meningeal artery, and the maxillary artery with their branches as the main arterial sources for the lateral and medial temporomandibular joint.

Conclusion: The direct volume rendering technique was found to be successful in the assessment of the arterial supply to the temporomandibular joint. The superficial temporal artery and maxillary artery ran along the lateral and medial sides of the condylar neck, suggesting that these arteries are at increased risk during soft-tissue procedures such as an elective arthroplasty of the temporomandibular joint.
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http://dx.doi.org/10.5624/isd.2013.43.1.37DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3604369PMC
March 2013

Effect of alkaline pH on staphylococcal biofilm formation.

APMIS 2012 Sep 11;120(9):733-42. Epub 2012 Apr 11.

Pharmaco-Biological Department, University of Messina, Italy.

Biofilms are a serious problem, cause of severe inconvenience in the biomedical, food and industrial environment. Staphylococcus aureus and S. epidermidis are important pathogenic bacteria able to form thick and resistant biofilms on various surfaces. Therefore, strategies aimed at preventing or at least interfering with the initial adhesion and subsequent biofilm formation are a considerable achievement. The aim of this study was to evaluate the effect of alkaline pH on bacterial adhesion and further biofilm formation of S. aureus and S. epidermidis strains by biofilm biomass, cell-surface hydrophobicity, scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM) analysis. The results demonstrated that the amount of biofilm biomass formed and the surface hydrophobicity were significantly less than what were observed at higher levels of pH. SEM and CLSM images revealed a poorly structured and very thin biofilm (2.5-3 times thinner than that of the controls). The inhibiting effect of the alkaline pH on the bacterial attachment impaired the normal development of biofilm that arrested at the microcolony stage. Alkaline formulations could be promising towards the control of bacterial colonization and therefore the reduction of the biofilm-related hazard. In the clinical setting, alkaline solutions or cleaners could be promising to prevent the bacterial colonization, by treating surfaces such as catheters or indwelling medical devices, reducing the risk of biofilm related infections.
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http://dx.doi.org/10.1111/j.1600-0463.2012.02900.xDOI Listing
September 2012

Expression of sarcoglycans in the human cerebral cortex: an immunohistochemical and molecular study.

Cells Tissues Organs 2012 27;196(5):470-80. Epub 2012 Jun 27.

Department of Biomorphology and Biotechnologies, University of Messina, Messina, Italy.

The sarcoglycan (SG) complex (SGC) is a subcomplex within the dystrophin-glycoprotein complex (DGC) and is composed of several transmembrane proteins (α, β, δ, γ, ε and ζ). The DGC supplies a transmembranous connection between the subsarcolemmal cytoskeleton networks and the basal lamina in order to protect the lipid bilayer and to provide a scaffold for signaling molecules in all muscle cells. In addition to its role in muscle tissue, dystrophin and some DGC components are expressed in neurons and glia. Very little is known about the SG subunits in the central nervous system (CNS) and some data suggested the presence of ε and ζ subunits only. In fact, mutations in the ε-SG gene cause myoclonus-dystonia, indicating its importance for brain function. To determine the presence and localization of SGC in the human cerebral cortex, we performed an investigation using immunofluorescence, immunoblotting and reverse transcriptase polymerase chain reaction. The results showed that all SG subunits are expressed in the human cerebral cortex, particularly in large neurons but also in astrocytes. These data suggest that the SG subcomplex may be involved in the organization of CNS synapses.
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http://dx.doi.org/10.1159/000336842DOI Listing
March 2013

Immunohistochemical analysis of TGF-β1 and VEGF in gingival and periodontal tissues: a role of these biomarkers in the pathogenesis of scleroderma and periodontal disease.

Int J Mol Med 2012 Sep 11;30(3):502-8. Epub 2012 Jun 11.

Department of Odontostomatology, School of Dentistry, University of Messina, Messina, Italy.

Periodontal disease is characterized by inflammation and bone loss. The balance between inflammatory mediators and their counter-regulatory molecules may be fundamental for determining the outcome of the immune pathology of periodontal disease. Transforming growth factor-β (TGF-β) and vascular endothelial growth factor (VEGF) represent a family of polypeptide proteins involved in the inflammation and regulation of immune responses, especially in rheumatic disease. The relationship between these growth factors and periodontitis has resulted in a new field of osteoimmunology and provides a context for better understanding the pathogenesis of periodontal disease. Therefore, the aim of this study was to compare the protein expression profile of these inflammatory mediators in 90 patients divided in three groups: healthy control, chronic periodontitis and in rheumatic disease, scleroderma. The findings presented here highlight that biomarkers, such as TGF-β1 and VEGF, play a key role in the evolution of the immune response, which in turn influences the outcome of disease establishment.
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http://dx.doi.org/10.3892/ijmm.2012.1024DOI Listing
September 2012

Expression of muscle-specific integrins in masseter muscle fibers during malocclusion disease.

Int J Mol Med 2012 Aug 30;30(2):235-42. Epub 2012 Apr 30.

Department of Biomorphology and Biotechnologies, Messina University, I-98125 Messina, Italy.

Integrins are heterodimeric cell surface membrane proteins linking the extracellular matrix to actin. α7B integrin is detected in proliferating and adult myofibers, whereas α7A plays a role in regenerating muscle fibers with a minor function in mature muscle fibers. The expression levels of β1A appear to be very low, whereas β1D appears to be the predominant integrin form in mature muscle. Considering the important features of masseter muscle we have studied integrin expression in masseter muscle specimens of surgical patients with posterior right crossbite and comparing them to left side masseter muscle specimens. Our results showed that the expression of integrins was significantly lower in the crossbite side muscle. Furthermore, the most important finding is that β1A is clearly detectable in adult masseter muscle. This behavior could be due to the particular composition of masseter, since it contains hybrid fibers showing the capacity to modify the contractile properties to optimize the energy efficiency or the action of the muscle during contraction. Moreover, masseter is characterized by a high turnover of muscle fibers producing a regeneration process. This may indicate a longer time to heal, justifying the loss of β1D and the consequential increase of β1A. Thus, our data provide the first suggestion that integrins in masseter muscle play a key role regulating the functional activity of muscle and allowing the optimization of contractile forces.
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http://dx.doi.org/10.3892/ijmm.2012.986DOI Listing
August 2012

Morphology and innervation of the teleost physostome swim bladders and their functional evolution in non-teleostean lineages.

Acta Histochem 2012 Dec 25;114(8):763-72. Epub 2012 Jan 25.

Department of Food and Environmental Science, Faculty of Science, University of Messina, Italy.

Swim bladders and lungs are homologous structures. Phylogenetically ancient actinopterygian fish such as Cladistians (Polypteriformes), Ginglymods (Lepisosteids) and lungfish have primitive lungs that have evolved in the Paleozoic freshwater earliest gnathostomes as an adaptation to hypoxic stress. Here we investigated the structure and the role of autonomic nerves in the physostome swim bladder of the cyprinid goldfish (Carassius auratus) and the respiratory bladder of lepisosteids: the longnose gar and the spotted gar (Lepisosteus osseus and L. oculatus) to demonstrate that these organs have different innervation patterns that are responsible for controlling different functional aspects. The goldfish swim bladder is a richly innervated organ mainly controlled by cholinergic and adrenergic innervation also involving the presence of non-adrenergic non-cholinergic (NANC) neurotransmitters (nNOS, VIP, 5-HT and SP), suggesting a simple model for the regulation of the swim bladder system. The pattern of the autonomic innervation of the trabecular muscle of the Lepisosteus respiratory bladder is basically similar to that of the tetrapod lung with overlapping of both muscle architecture and control nerve patterns. These autonomic control elements do not exist in the bladders of the two species studied since they have very different physiological roles. The ontogenetic origin of the pulmonoid swim bladder (PSB) of garfishes may help understand how the expression of these autonomic control substances in the trabecular muscle is regulated including their interaction with the corpuscular cells in the respiratory epithelium of this bimodal air-breathing fish.
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http://dx.doi.org/10.1016/j.acthis.2012.01.003DOI Listing
December 2012

Impact of hepatitis B virus (HBV) preS/S genomic variability on HBV surface antigen and HBV DNA serum levels.

Hepatology 2012 Aug 13;56(2):434-43. Epub 2012 Jul 13.

Unit of Clinical and Molecular Hepatology, Department of Internal Medicine, University of Messina, Messina, Italy.

Unlabelled: To evaluate whether hepatitis B virus (HBV) preS/S gene variability has any impact on serum hepatitis B surface antigen (HBsAg) levels and to analyze the replication capacity of naturally occurring preS/S variants, sera from 40 untreated patients with HBV-related chronic liver disease (hepatitis B e antigen [HBeAg]-positive, n = 11; HBeAg-negative, n = 29) were virologically characterized. Additionally, phenotypic analysis of three different preS/S variant isolates (carrying a 183-nucleotide deletion within the preS1 region, the deletion of preS2 start codon, and a stop signal at codon 182 within the S gene, respectively) was performed. HBV infecting 14 (35%) patients had single or multiple preS/S genomic mutations (i.e., preS1 and/or preS2 deletions, preS2 start codon mutations, C-terminally truncated and/or "a" determinant mutated S protein). Presence of preS/S variants negatively correlated with HBsAg titers (r = -0.431; P = 0.005) and its prevalence did not significantly differ between HBeAg-positive and HBeAg-negative patients. No correlation was found between HBsAg and HBV DNA levels in patients infected with preS/S mutants, whereas a significant correlation was found between HBsAg and viremia levels (r = 0.607; P = 0.001) in patients infected with wild-type HBV strains. HepG2 cells replicating the above-mentioned three preS/S variants showed significant reduction of HBsAg secretion, retention of envelope proteins in the endoplasmic reticulum, less efficient virion secretion and nuclear accumulation of significantly higher amounts of covalently closed circular DNA compared with wild-type HBV replicating cells.

Conclusion: In patients infected with preS/S variants, HBV DNA replication and HBsAg synthesis/secretion appear to be dissociated. Therefore, the use of HBsAg titer as diagnostic/prognostic tool has to take into account the frequent emergence of preS/S variants in chronic HBV infection.
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http://dx.doi.org/10.1002/hep.25592DOI Listing
August 2012

Costameric proteins: from benchside to future translational cardiovascular research.

Ann Cardiol Angeiol (Paris) 2012 Feb 27;61(1):55-60. Epub 2011 Dec 27.

Department of Biomorphology and Biotechnologies, School of Medicine, University of Messina, Messina, Italy.

Costameres encircle the myocyte perpendicular to its long axis, and comprise two protein complexes: the dystrophin-glycoprotein complex (DGC) and the vinculin-talin-integrin system. They participate in signaling functions and protect muscle cells from damage induced by workload. The behaviour of those proteins has been a focus of study starting from skeletal and smooth muscle cells to cardiomyocytes, and still represents a topical subject for cardiovascular translational research. This review summarizes the past and present novel approaches of our and other groups of work on this subject of research.
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http://dx.doi.org/10.1016/j.ancard.2011.12.003DOI Listing
February 2012

Sarcoglycans in the normal and pathological breast tissue of humans: an immunohistochemical and molecular study.

Cells Tissues Organs 2012 8;195(6):550-62. Epub 2011 Nov 8.

Department of Biomorphology and Biotechnologies, University of Messina, Italy.

The sarcoglycan complex, consisting of α-, β-, γ-, δ- and ε-sarcoglycans, is a multimember transmembrane system providing a mechanosignaling connection from the cytoskeleton to the extracellular matrix. Whereas the expression of α- and γ-sarcoglycan is restricted to striated muscle, other sarcoglycans are widely expressed. Although many studies have investigated sarcoglycans in all muscle types, insufficient data are available on the distribution of the sarcoglycan complex in nonmuscle tissue. On this basis, we used immunohistochemical and RT-PCR techniques to study preliminarily the sarcoglycans in normal glandular breast tissue (which has never been studied in the literature on these proteins) to verify the effective wider distribution of this complex. Moreover, to understand the role of sarcoglycans, we also tested samples obtained from patients affected by fibrocystic mastopathy and breast fibroadenoma. Our data showed, for the first time, that all sarcoglycans are always detectable in all normal samples both in epithelial and myoepithelial cells; in pathological breast tissue, all sarcoglycans appeared severely reduced. These data demonstrated that all sarcoglycans, not only β-, δ-, and ε-sarcoglycans, have a wider distribution, implying a new unknown role for these proteins. Moreover, in breast diseases, sarcoglycans containing cadherin domain homologs could provoke a loss of strong adhesion between epithelial cells, permitting and facilitating the degeneration of these benign breast tumors into malignant tumors. Consequently, sarcoglycans could play an important and intriguing role in many breast diseases and in particular in tumor progression from benign to malignant.
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http://dx.doi.org/10.1159/000329508DOI Listing
November 2012

Altered cytoskeletal structure of smooth muscle cells in ureteropelvic junction obstruction.

J Urol 2011 Jun 21;185(6):2314-9. Epub 2011 Apr 21.

Department of Biomorphology and Biotechnology, University of Messina, Messina, Italy.

Purpose: Ureteropelvic junction obstruction is one of the most common causes of hydronephrosis in children. A malfunction of smooth muscle cells is believed to be the underlying mechanism causing obstruction. We investigated the expression of some integrins, talin and β-dystroglycan, considered the main compound of smooth muscle cell cytoskeleton, and active caspase 3 at the level of the ureteropelvic junction obstruction.

Materials And Methods: Specimens were obtained at pyeloplasty in 12 children with ureteropelvic junction obstruction. Six control specimens were obtained during organ explantation. Specimens were divided into renal pelvis, ureteropelvic junction and ureter below the obstruction. Western blot analysis of active caspase 3, and immunofluorescence and polymerase chain reaction analysis were performed for α7A, β1A, α7B and β1D integrins, talin and β-dystroglycan.

Results: Talin and β-dystroglycan were slightly impaired in ureteropelvic junction obstruction, while α7B and β1D integrins were severely reduced, and α7A, β1A and active caspase 3 were significantly enhanced compared to controls.

Conclusions: We demonstrated activation of apoptosis and a critical alteration of cytoskeleton that might explain the altered function and the increased apoptosis in smooth muscle cells in ureteropelvic junction obstruction. The delayed rearrangement of the cytoskeleton of smooth muscle cells in ureteropelvic junction obstruction might be linked to a postnatal splicing from α7A and β1A to α7B and β1D integrins, respectively. This relationship could explain the common clinical scenario of spontaneous improvement of hydronephrosis in children with suspected ureteropelvic junction obstruction.
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http://dx.doi.org/10.1016/j.juro.2011.02.045DOI Listing
June 2011

Localization of neurotransmitters, peptides and nNOS in the pseudobranchial neurosecretory cell system and associated carotid labyrinth of the catfish, Clarias batrachus.

Acta Histochem 2012 Jan 12;114(1):62-7. Epub 2011 Mar 12.

Department of Animal Biology and Marine Ecology, Faculty of Science, University of Messina, Italy.

The carotid labyrinth is an enigmatic endocrine structure of unknown chemosensory function lying in the gill region of the catfishes. The carotid body is found at the carotid bifurcation of amphibians and all mammalian vertebrates on the evolutionary tree. It is a vascular expansion comprised of a cluster of glomus cells with associated (afferent and efferent) innervations. In the catfish species studied (Clarias batrachus) a neurosecretory cell system consisting of pseudobranchial neurosecretory cells connect the carotid labyrinth or large vessels (both the efferent branchial artery and dorsal aorta), and is likely akin to the glomus cells, but comparing these structures in widely divergent vertebrate species, the conclusion is that the structural components are more elaborate than those of terrestrial vertebrates. However, these cells reveal both an endocrine phenotype (such as the association with capillaries and large vessels) and the presence of regulatory substances such as neurotransmitters and neuropeptides producing good evidence for high levels of conservation of these substances that are present in the glomus cells of mammalian vertebrates. VIP-immunopositive neuronal cell bodies are detected in the periphery of the carotid labyrinth. They are presumptive local neurons that differ from pseudobranchial neurosecretory cells, the latter failing to express VIP in their soma.
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http://dx.doi.org/10.1016/j.acthis.2011.02.005DOI Listing
January 2012

Morphometrical and morphological analysis of lateral ventricles in schizophrenia patients versus healthy controls.

Psychiatry Res 2010 Jul 9;183(1):52-8. Epub 2010 Jun 9.

Unit of Psychiatry, Department of Neurosciences, University of Messina, Italy.

The goal of this report was to highlight lateral ventricle morphology and volume differences between schizophrenia patients and matched controls. Subjects identified as suitable for analysis comprised 15 schizophrenia patients and 15 healthy subjects. The method applied is three-dimensional (3D) volume rendering starting from structural magnetic resonance imaging (MRI) studies of selected ventricular regions. Differences between groups relative to the global ventricular system and its subdivisions were found. Total lateral ventricle volume, right ventricle volume and left ventricle volume were all higher in schizophrenia patients than in controls; unilateral differences between the two groups were also outlined (right ventricle volume>left ventricle volume in schizophrenia patients vs. healthy subjects). Furthermore, occipital and frontal horn enlargement was found in schizophrenia patients compared with normal controls, but the difference in the temporal horn was not statistically significant. A substantial difference was noted in lateral ventricle morphology between the two groups. Our findings were consistent with the literature and may shed light on some of the discrepancies in previous reports on differences in lateral ventricle volume enlargement.
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http://dx.doi.org/10.1016/j.pscychresns.2010.01.014DOI Listing
July 2010

Immunohistochemial evaluation of sarcoglycans and integrins in gingival epithelium of multiple myeloma patients with bisphosphonate-induced osteonecrosis of the jaw.

Oncol Rep 2010 Jul;24(1):129-34

Division of Maxillofacial Surgery, University of Messina, Messina, Italy.

Osteonecrosis of the jaw (ONJ) is an adverse outcome associated to bisphosphonate treatment. However, it is not known whether the ONJ lesion originates in the bone, or whether it may initiate in the oral mucosa. The aim of our study was to evaluate the pattern of basal lamina of oral mucosa after bisphosphonate administration and to analyze the structural damage of the mucosa in ONJ patients, and in subjects treated with bisphosphonates without osteonecrosis. By immunohistochemistry, we evaluated changes in basement membrane by expression of signalling proteins, laminin, and type IV collagen. All tested proteins were almost absent in basal lamina and mucosa of subjects treated with bisphosphonates without osteonecrosis, whereas in mucosa of patients with ONJ, they showed a clearly detectable pattern of the same proteins, specifically in basal lamina, but less in comparison to control samples. Moreover, in pathological mucosa, the clearly detectable staining pattern for VEGF indicated a massive neoangiogenesis. Bisphosphonates induce changes in expression of proteins also in oral mucosa. The increase of these proteins in basal lamina, and the neo-angiogenesis, concomitant with formation of the lesion, could indicate a compensative behaviour in the remodelling of the gingival mucosa in order to restore the epithelial architecture.
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http://dx.doi.org/10.3892/or_00000837DOI Listing
July 2010

Intracellular accumulation of cell cycle regulatory proteins and nucleolin re-localization are associated with pre-lethal ultrastructural lesions in circulating T lymphocytes: the HIV-induced cell cycle dysregulation revisited.

Cell Cycle 2010 Jun 1;9(11):2130-40. Epub 2010 Jun 1.

Department of Hygiene, Public Health and Preventive Medicine, University of Messina, Messina, Italy.

The HIV-induced demise of CD4-T cells is thought to be a result of the execution of genetically programmed cell death that occurs in lymphoid tissue, where many resident T cells are chronically hyperactivated. Since HIV-induced alterations of cell cycle control has been often indicated as prominent mechanism of immune hyper activation and cause of apoptotic death, the signal pathway involved in cell cycle dysregulation of T lymphocytes from HIV infected patients was extensively studied. Here, we also demonstrate that circulating T lymphocytes leave lymphoid tissues with diffused regressive lesions (vacuolization, blebbing, nuclear evanescence and organelle swelling). Equally diffused are biochemical anomalies that accompany the overall disarrangement of cell structure, particularly the fragmentation and diffusion into the cytoplasm of C23/nucleolin, the intracellular accumulation of short lived regulatory proteins and the decrease in expression of membrane proteins. All this is something more than a cell cycle-related remodelling of cell morphology and biochemical mechanisms, and rather recalls a necrotic/oncotic cell damage. Since these changes are associated with adaptive mechanisms to hypoxia, we give evidence for alteration of cell cycle control developing in conditions of scarce energy supply.
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http://dx.doi.org/10.4161/cc.9.11.11754DOI Listing
June 2010

Hemispheric prevalence during chewing in normal right-handed and left-handed subjects: a functional magnetic resonance imaging preliminary study.

Cranio 2010 Apr;28(2):114-21

University of Turin, Dental School, Via Nizza 230, 10126 Torino, Italy.

This study evaluated the activation of different cortical areas during nondeliberate chewing of soft and hard boluses in five right-handed and five left-handed subjects with normal occlusion, to determine different hemispheric prevalences. The study was conducted with a functional Magnetic Resonance Imaging (1.5 T Magnetom Vision - Siemens Medical, Germany) using a head coil. The results showed that the most frequently activated areas were Brodmann's areas four and six in the primary motor and premotor cortex, the insula and Broca's area and, overall, showed greater activity of the cortical mastication area (CMA) in the right hemisphere for right-handed and in the left hemisphere for left-handed subjects.
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http://dx.doi.org/10.1179/crn.2010.016DOI Listing
April 2010

Abnormal distribution of sarcoglycan subcomplex in colonic smooth muscle cells of aganglionic bowel.

Int J Mol Med 2010 Mar;25(3):353-9

Department of Pediatric Surgery, Unit of Pediatric Surgery, University of Catania, Vittorio Emanuele Hospital, 95124 Catania, Italy.

Hirschsprung's disease (HD) is a development disorder of the enteric nervous system in which the altered innervation explains the inability of the aganglionic segment to relax. Impairment of cytoskeleton in SMC of aganglionic bowel has been shown. Sarcoglycan subcomplex (SG) may support the development and maintenance of muscle cells. We examined the SG subunit expression in colonic aganglionic and ganglionic specimens obtained from patients with HD. Full-thickness bowel specimens were obtained from six patients with HD. Six normal colon specimens were used as controls. Immunofluorescent analysis and reverse transcriptase polymerase chain reaction evaluation were performed for alpha-, beta-, gamma-, delta- and epsilon-SG. In control colon, the indirect immunofluorescence showed a strong staining pattern of beta- gamma- delta- and epsilon-SG while a weak positivity of alpha-SG was recorded. In aganglionic bowel, immunofluorescence intensity values documented a significant lack of epsilon-SG while an enhanced alpha-SG, coupled to a loss of epsilon-SG, was recorded in ganglionic bowel in HD-affected patients. Our observations underscore the assumption that non-neuronal elements of the colon might play a key role in the pathogenesis of HD and loss of epsilon-SG might critically alter the cytoskeleton in the aganglionic bowel segment. Up-regulation of alpha-SG is probably an acquired phenomenon to reinforce the sarcolemma and to perform a forceful contraction in dilated ganglionic HD-affected colon, related to chronic pseudo-obstruction, contributing to the intestinal dysmotility that persists in 20% of patients after resection of the aganglionic bowel.
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http://dx.doi.org/10.3892/ijmm_00000352DOI Listing
March 2010

Three-dimensional volume rendering of the ankle based on magnetic resonance images enables the generation of images comparable to real anatomy.

J Anat 2009 Nov 12;215(5):592-9. Epub 2009 Aug 12.

Department of Biomorphology and Biotechnologies, School of Medicine, University of Messina, Messina, Italy.

We have applied high-quality medical imaging techniques to study the structure of the human ankle. Direct volume rendering, using specific algorithms, transforms conventional two-dimensional (2D) magnetic resonance image (MRI) series into 3D volume datasets. This tool allows high-definition visualization of single or multiple structures for diagnostic, research, and teaching purposes. No other image reformatting technique so accurately highlights each anatomic relationship and preserves soft tissue definition. Here, we used this method to study the structure of the human ankle to analyze tendon-bone-muscle relationships. We compared ankle MRI and computerized tomography (CT) images from 17 healthy volunteers, aged 18-30 years (mean 23 years). An additional subject had a partial rupture of the Achilles tendon. The MRI images demonstrated superiority in overall quality of detail compared to the CT images. The MRI series accurately rendered soft tissue and bone in simultaneous image acquisition, whereas CT required several window-reformatting algorithms, with loss of image data quality. We obtained high-quality digital images of the human ankle that were sufficiently accurate for surgical and clinical intervention planning, as well as for teaching human anatomy. Our approach demonstrates that complex anatomical structures such as the ankle, which is rich in articular facets and ligaments, can be easily studied non-invasively using MRI data.
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http://dx.doi.org/10.1111/j.1469-7580.2009.01133.xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2780576PMC
November 2009

Dystrophin-glycoprotein complex and vinculin-talin-integrin system in human adult cardiac muscle.

Int J Mol Med 2009 Feb;23(2):149-59

Department of Biomorphology and Biotechnologies, University of Messina, Messina, Italy.

Costameres were identified, for the first time, in skeletal and cardiac muscle, as regions associated with the sarcolemma, consisting of densely clustered patches of vinculin; they have many characteristics common to the cell-extracellular matrix-type of adherens junctions. Costameres are considered 'proteic machinery' and they appear to comprise two protein complexes, the dystrophin-glycoprotein complex (DGC) and the vinculin-talin-integrin system. In comparison to skeletal muscle, few studies have focused on cardiac muscle regarding these two complexes, and study is generally relative to dystrophin or to cardiac diseases, such as cardiomyopathies. However, insufficient data are available on these proteins in healthy human cardiomyocytes. For this reason, we performed an immunohistochemical study using human cardiac muscle fibers, in order to define the real distribution and the spatial relationship between the proteins in these two complexes. Our data showed a real costameric distribution of DGC and of the vinculin-talin-integrin system; all tested proteins were present in T-tubule and in intercalated disks. Moreover, our data demonstrated that all tested proteins of DGC colocalized with each other, as all tested components of the vinculin-talin-integrin system, and that all tested proteins of DGC colocalized with all tested proteins of the vinculin-talin-integrin system. Finally, all tested proteins of the two complexes were localized in the region of the sarcolemma over the I band, in 100% of our observations. The present study, for the first time, analyzed the majority of proteins of DGC and of the vinculin-talin-integrin system in cardiac muscle fibers, and it confirmed that DGC and the vinculin-talin-integrin system have a role in the transduction of mechanical force to the extracellular matrix. Finally it attributed a key role in the regulation of action potential duration to cardiac myocytes.
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February 2009