Publications by authors named "Giuseppina Rizzo"

37 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

Histological and Immunofluorescence Study of Discal Ligaments in Human Temporomandibular Joint.

J Funct Morphol Kinesiol 2020 Dec 8;5(4). Epub 2020 Dec 8.

Department of Clinic and Experimental Medicine, University of Messina, 98122 Messina, Italy.

The temporomandibular joint (TMJ) is a bilateral synovial articulation stabilized by several anatomical structures such as ligaments. The existence of articular capsule reinforcement structures have been described in the lateral and medial sides of disc which have been defined as collateral ligaments, lateral and medial. Despite that, some macroscopic observations support that these collateral ligaments do not belong to the articular capsule but they belong to the disc. By that, the aim of the present work was to evaluate morphological aspects of TMJ from cadaveric frozen heads by histological and immunofluorescence techniques in order to verify the origin and insertion of lateral and medial collateral ligaments. Results show that both lateral and medial ligaments origin from the disc and insert directly to the articular cartilage of mandibula condyle. These data open a new approach in the study of human TMJ.
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http://dx.doi.org/10.3390/jfmk5040090DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7804866PMC
December 2020

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

In Vivo Computed Tomography Direct Volume Rendering of the Anterior Ethmoidal Artery: A Descriptive Anatomical Study.

Int Arch Otorhinolaryngol 2020 Jan 9;24(1):e38-e46. Epub 2020 Jan 9.

Scientific Institute for Research, Hospitalization and Health Care Centro Neurolesi Bonino Pulejo, Messina, Italy.

 The clinical relevance of the anatomy and variations of the anterior ethmoidal artery (AEA) is outstanding, considering its role as a landmark in endoscopic surgery, its importance in the therapy of epistaxis, and the high risks related to iatrogenic injuries.  To provide an anatomical description of the course and relationships of the AEA, based on direct computed-tomography (CT)-based 3D volume rendering.  Direct volume rendering was performed on 18 subjects who underwent (CT) with contrast medium for suspected cerebral aneurism.  The topographical location of 36 AEAs was assessed as shown: 10 dehiscent (27.8%), 20 intracanal (55.5%), 6 incomplete canals (16.7%). Distances from important topographic landmarks are reported.  This work demonstrates that direct 3D volume rendering is a valid imaging technique for a detailed description of the anterior ethmoidal artery thus representing a useful tool for head pre-operatory assessments.
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http://dx.doi.org/10.1055/s-0039-1698776DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6952292PMC
January 2020

The Cortico-Basal Ganglia-Cerebellar Network: Past, Present and Future Perspectives.

Front Syst Neurosci 2019 30;13:61. Epub 2019 Oct 30.

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

Much of our present understanding of the function and operation of the basal ganglia rests on models of anatomical connectivity derived from tract-tracing approaches in rodents and primates. However, the last years have been characterized by promising step forwards in the investigation and comprehension of brain connectivity in humans. The aim of this review is to revise the current knowledge on basal ganglia circuits, highlighting similarities and differences across species, in order to widen the current perspective on the intricate model of the basal ganglia system. This will allow us to explore the implications of additional direct pathways running from cortex to basal ganglia and between basal ganglia and cerebellum recently described in animals and humans.
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http://dx.doi.org/10.3389/fnsys.2019.00061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6831548PMC
October 2019

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

The cortico-rubral and cerebello-rubral pathways are topographically organized within the human red nucleus.

Sci Rep 2019 08 20;9(1):12117. Epub 2019 Aug 20.

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

The Red Nucleus (RN) is a large nucleus located in the ventral midbrain: it is subdivided into a small caudal magnocellular part (mRN) and a large rostral parvocellular part (pRN). These distinct structural regions are part of functionally different networks and show distinctive connectivity features: the mRN is connected to the interposed nucleus, whilst the pRN is mainly connected to dentate nucleus, cortex and inferior olivary complex. Despite functional neuroimaging studies suggest RN involvement in complex motor and higher order functions, the pRN and mRN cannot be distinguished using conventional MRI. Herein, we employ high-quality structural and diffusion MRI data of 100 individuals from the Human Connectome Project repository and constrained spherical deconvolution tractography to perform connectivity-based segmentation of the human RN. In particular, we tracked connections of RN with the inferior olivary complex, the interposed nucleus, the dentate nucleus and the cerebral cortex. We found that the RN can be subdivided according to its connectivity into two clusters: a large ventrolateral one, mainly connected with the cerebral cortex and the inferior olivary complex, and a smaller dorsomedial one, mainly connected with the interposed nucleus. This structural topography strongly reflects the connectivity patterns of pRN and mRN respectively. Structural connectivity-based segmentation could represent a useful tool for the identification of distinct subregions of the human red nucleus on 3T MRI thus allowing a better evaluation of this subcortical structure in healthy and pathological conditions.
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http://dx.doi.org/10.1038/s41598-019-48164-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6702172PMC
August 2019

Structural connectivity-based topography of the human globus pallidus: Implications for therapeutic targeting in movement disorders.

Mov Disord 2019 07 11;34(7):987-996. Epub 2019 May 11.

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

Background: Understanding the topographical organization of the cortico-basal ganglia circuitry is of pivotal importance because of the spreading of techniques such as DBS and, more recently, MR-guided focused ultrasound for the treatment of movement disorders. A growing body of evidence has described both direct cortico- and dento-pallidal connections, although the topographical organization in vivo of these pathways in the human brain has never been reported.

Objective: To investigate the topographical organization of cortico- and dento-pallidal pathways by means of diffusion MRI tractography and connectivity based parcellation.

Methods: High-quality data from 100 healthy subjects from the Human Connectome Project repository were utilized. Constrained spherical deconvolution-based tractography was used to reconstruct structural cortico- and dento-pallidal connectivity. Connectivity-based parcellation was performed with a hypothesis-driven approach at three different levels: functional regions (limbic, associative, sensorimotor, and other), lobes, and gyral subareas.

Results: External globus pallidus segregated into a ventral associative cluster, a dorsal sensorimotor cluster, and a caudal "other" cluster on the base of its cortical connectivity. Dento-pallidal connections clustered only in the internal globus pallidus, where also associative and sensorimotor clusters were identified. Lobar parcellation revealed the presence in the external globus pallidus of dissociable clusters for each cortical lobe (frontal, parietal, temporal, and occipital), whereas in internal globus pallidus only frontal and parietal clusters were found out.

Conclusion: We mapped the topographical organization of both internal and external globus pallidus according to cortical and cerebellar connections. These anatomical data could be useful in DBS, radiosurgery and MR-guided focused ultrasound targeting for treating motor and nonmotor symptoms in movement disorders. © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
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http://dx.doi.org/10.1002/mds.27712DOI Listing
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

Human calf muscles changes after strength training as revealed by diffusion tensor imaging.

J Sports Med Phys Fitness 2019 May 18;59(5):853-860. Epub 2018 Jul 18.

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

Background: Diffusion tensor imaging (DTI) is a non-invasive MR technique widely employed to study muscle anatomy. DTI parameters have been used to investigate microstructural changes dependent on demographic factors or transient condition such as exercise. The present study is aimed at investigating the diffusion parameters changes of the human calf muscles after a 3-months strength training protocol.

Methods: Ten young men were trained for improving size and strength of the medial (GCM), lateral gastrocnemius (GCL) and soleus (SL) three times a week, with at least 24 hours between training sessions, for a period of three months. Diffusion weighted magnetic resonance images were acquired at the beginning of the training period (TPRE) and at three months (TPOST) using a 3T scanner. The fractional anisotropy (FA), mean diffusivity (MD) and tensor eigenvalues (λ1, λ2, λ3) were derived from the diffusion weighted imaging data.

Results: We found a significant increase in λ1, λ2, λ3 and MD values and muscle volumes between TPRE and TPOST in all the examined muscles both for the left and right side. No significant differences were highlighted for FA.

Conclusions: DTI enables the investigation of muscle microstructure, allowing for the assessment of diffusion parameters variation of the muscle tissue in response to training thus being a useful tool to investigate physiological and pathological changes in skeletal muscle microstructure which could be employed to test the outcomes and the effectiveness of a given training protocol.
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http://dx.doi.org/10.23736/S0022-4707.18.08759-5DOI Listing
May 2019

Claustral structural connectivity and cognitive impairment in drug naïve Parkinson's disease.

Brain Imaging Behav 2019 Aug;13(4):933-944

IRCCS Centro Neurolesi Bonino Pulejo, S.S. 113 - Contrada Casazza, 98124, Messina, Italy.

The claustrum is a thin grey matter structure which is involved in a wide brain network. Previous studies suggested a link between claustrum and Parkinson's Disease (PD), showing how α-synuclein pathology may affect claustral neurons as well as how α-synuclein immunoreactivity may correlate with the onset of cognitive dysfunctions. Our aim is to investigate, via diffusion MRI, claustral structural network changes in drug naïve PD patients, with the goal to understand whether such changes may contribute to cognitive decline in PD. 15 drug naïve PD patients and 15 age-matched controls were enrolled; MR protocol was performed on a 3T scanner. Whole brain probabilistic tractography was obtained using Constrained Spherical Deconvolution (CSD) diffusion model. Connectivity matrices were estimated based on a robust anatomical parcellation of structural T1w images. In PD group, impaired subnetworks were correlated with psychological examinations. We found decreased claustral connectivity in PD patients compared to controls, especially with areas mainly involved in visuomotor and attentional systems. Moreover, we found a positive correlation between MoCA and density of pathways connecting ipsilaterally claustrum to left (r = 0.578, p = 0.021) and right (r = 0.640, p = 0.020) Pars Orbitalis. Our results support the hypothesis of claustral involvement in cognitive decline in drug naïve PD patients.
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http://dx.doi.org/10.1007/s11682-018-9907-zDOI Listing
August 2019

The Limbic and Sensorimotor Pathways of the Human Amygdala: A Structural Connectivity Study.

Neuroscience 2018 08 15;385:166-180. Epub 2018 Jun 15.

Department of Biomedical, Dental Sciences and Morphological and Functional Images, University of Messina, Italy; IRCCS Centro Neurolesi "Bonino-Pulejo", Messina, Italy. Electronic address:

The amygdala plays a key role in gathering social cues to context-appropriate responses that require refined motor behavior, involving either direct or indirect connections with sensorimotor-related areas. Although, several studies investigated the structural and functional limbic connectivity of the amygdala both in animals and in humans, less is known about the limbic modulation on sensorimotor-related areas. However, recent evidences suggest the amygdala as a possible cornerstone in the limbic-motor interface. Herein, we used high-resolution diffusion data of the Massachusetts General Hospital-University of Southern California (MGH-USC) Adult Diffusion Dataset, constrained spherical deconvolution-based signal modeling and probabilistic tractography aimed at identifying and reconstructing the connectivity patterns linking the amygdala to the limbic- and sensorimotor-related areas. As regards the limbic network, our results showed that the amygdala has high probability to be connected with the fusiform gyrus and the lateral orbitofrontal cortex. On the other hand, our connectomic analysis revealed a close interplay between the amygdala and the inferior parietal lobule, followed by the postcentral gyrus, the precentral gyrus and the paracentral lobule. The findings of the present study are in line with previous literature and reinforce the idea of the existence of a limbic-motor interface, which is likely to be involved in the emotional modulation of complex functions such as spatial perception and movement computation. Considering that these pathways may play an important role, not on in physiological conditions, but also in pathological context, further studies should be fostered in order to confirm the existence of a limbic-motor interface and its precise functional meaning.
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http://dx.doi.org/10.1016/j.neuroscience.2018.05.051DOI Listing
August 2018

High values of pelvic incidence: A possible risk factor for zigoapophyseal facet arthrosis in young.

J Orthop 2018 Jun 21;15(2):333-336. Epub 2018 Feb 21.

A.O.N. SS Antonio e Biagio e Cesare Arrigo, Alessandria, Italy.

In humans the acquisition of the bipedalism caused different structural changes to achieve the new functional demands. In particular, several changes have occurred in the spine and pelvis. In recent years the sagittal morphology of the spine and pelvis has become one of the most focused topics in spine research. The sample consists of 348 volunteers, with no history of low back pain, without any previous major trauma at the spine or at the pelvis. Aged between 20 and 29 years. The presence and severity of zygoapophyseal facet arthrosis were investigated in accordance with Pathria's classification (it considered four parameters: width of interarticular space, the presence of osteophytes, the presence of facet hypertrophy and presence of areas of bone erosion). Volunteers were divided into two group based on sagittal balance subtype classified by Roussouly in 2005. 98 volunteers (35.76%) belongs to group A (subtype I and II), and 176 volunteers (64.24%) belongs to group III and IV. The different weight distribution in the lumbar spine suggests that different subtype of sagittal balance could develop zygoapophyseal facet arthrosis more frequently. Considering the different Groups, a statistically significant difference was found: people belonging in group B (subtype III and IV), shows a prevalence of 36,36% compared with a prevalence of 24.5% for group A (subtype I and II).
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http://dx.doi.org/10.1016/j.jor.2018.02.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5990124PMC
June 2018

Anatomical differences in the bony structure of L5 and L4: A possible classification according to the lateral tilt of the pedicles.

J Orthop 2018 Mar 30;15(1):205-209. Epub 2018 Jan 30.

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

The aim of this study is to underline the necessity of a better knowledge of pedicles anatomy in order to improve surgical treatment of spine disorders such us low back pain, spinal fractures and scholiosis. A classification of pedicles lateral tilt which could help surgeons before the application of screws during transpedicular fixation is reported. Anatomical differences in the orientiation of the pedicles of L5 and L4 have been found. For each patient that met the inclusion criteria underwent: Radiography of the lumbo-sacral region, CT examination, MRI acquisition. Patients were divided into three categories thanks to 3D direct volume rendering of CT scan. Subjects belonged to W-Type, V-Type and U-type depending on their morphometric features. The subdivision was further implemented with measurements of the distance between pedicles and adjacent nervous structures. Concerning L5, W-Type (WT) exhibited a lateral tilt of L5 larger than 36°, V-Type exhibited a lateral tilt of L5 from 30° to 36°, U-type exhibited a lateral tilt of L5 smaller than 30°. Concerning L4, WT exhibited a lateral tilt of 28.4°, VT exhibited a lateral tilt of of 25.1, UT exhibited a lateral tilt of 22.2°; we assume that the degree of lateralization of L4 depends on the one of L5. The way the screw is applied during surgical treatment is clinically relevant, thus our classification may be very useful in order to decrease surgical risk and improve conditions of patients after surgical treatment.
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http://dx.doi.org/10.1016/j.jor.2018.01.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5895899PMC
March 2018

Analysis on sarcoglycans expression as markers of septic cardiomyopathy in sepsis-related death.

Int J Legal Med 2018 Nov 11;132(6):1685-1692. Epub 2018 Apr 11.

Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, via Consolare Valeria, 1, 98125, Messina, Italy.

The post-mortem assessment of sepsis-related death can be carry out by many methods recently suggested as microbiological and biochemical investigations. In these cases, the cause of death is a multiple organ dysfunction due to a dysregulated inflammatory response occurring after the failure of infection control process. It was highlighted also that the heart can be a target organ in sepsis which determines the so-called septic cardiomyopathy characterized by myocardial depression. Several mechanisms to explain the pathophysiology of septic cardiomyopathy were suggested, but very few studies about the structural alterations of cardiac cells responsible for myocardial depression were carried out. The aim of this study was to evaluate whether sarcoglycans (SG) were involved in septic cardiac damage analyzing their expression in sepsis-related deaths and, particularly, if these proteins can be used as markers of septic myocardial dysfunction. Cases of septic-related death confirmed by clinical and autopsy records were investigated and compared to a control group of traumatic deaths. Indirect immunofluorescence analysis was performed to analyze α-SG, β-SG, δ-SG, ζ-SG, ε-SG, and γ-SG. Decrease of fluorescence staining pattern for all tested sarcoglycans was observed in the septic-related deaths compared to normal fluorescence staining pattern of control group. These results provide new findings about the myocytes structural alterations due to sepsis and suggest that these proteins could be used in forensic assessment of septic cardiomyopathy.
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http://dx.doi.org/10.1007/s00414-018-1840-6DOI Listing
November 2018

Role of Genetic Background in Cardiovascular Risk Markers Changes in Water Polo Players.

Int J Sports Med 2018 May 21;39(5):390-396. Epub 2018 Mar 21.

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

Methylene-tetrahydrofolate reductase (MTHFR) and paraoxonase 1 (PON1) gene polymorphisms have been associated with hyperhomocysteinemia and oxidative stress increase, that are established cardiovascular risk factors. Given that intense physical activity may increase the susceptibility to adverse cardiovascular outcomes, here we investigated the effects of MTHFR C677T and A1298C as well as PON1 Q192R gene polymorphisms on cardiovascular risk markers in twenty-eight male water polo elite players. The mean plasma levels of homocysteine (Hcy) and advanced oxidation protein products (AOPP) were above reference limits in resting conditions, and increased after competition. Moreover, a positive correlation was found between Hcy and AOPP concentrations, and also between their variations (ratio post-exercise/pre-exercise values) and the variations of lactic dehydrogenase (LDH) and creatine kinase (CK) activities, known as muscle damage markers. The highest Hcy and AOPP values were found in subjects having either MTHFR CT/AC or TT/AA, and PON1 QR192 genotype, respectively. After exercise, Hcy concentrations significantly increased in CT/AC or TT/AA subjects than in athletes having other MTHFR genotypes. A training-induced increase in plasma levels of LDH and CK activities, as well as myoglobin concentrations, was also observed, even if significant differences were found only for CK activity in athletes with MTHFR CT/AC or TT/AA athletes.
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http://dx.doi.org/10.1055/s-0044-101459DOI Listing
May 2018

Differential Expression of Nitric Oxide Synthase Isoforms nNOS and iNOS in Patients with Non-Segmental Generalized Vitiligo.

Int J Mol Sci 2017 Nov 26;18(12). Epub 2017 Nov 26.

Department of Clinical and Experimental Medicine, University of Messina, Via Consolare Valeria, 98124 Messina, Italy.

Nitric oxide (NO) is involved in several biological processes, but its role in human melanogenesis is still not well understood. Exposure to UVA and UVB induces nitric oxide production in keratinocytes and melanocytes through the activation of constitutive nitric oxide synthase, increasing tyrosinase activity and melanin synthesis, whereas inducible nitric oxide synthase over expression might be involved in hypopigmentary disorders. The aim of this study was to evaluate whether inducible nitric oxide synthase and neuronal nitric oxide synthase expression were modified in vitiligo skin compared to healthy controls. Skin biopsies were obtained from inflammatory/lesional and white/lesional skin in 12 patients with active, non-segmental vitiligo; site-matched biopsies of normal skin from eight patients were used as controls. Nitric oxide synthase isoforms expression was evaluated by confocal laser scanning microscopy and Western Blot analysis. Inducible nitric oxide synthase expression was significantly increased in inflammatory/lesional skin compared to healthy skin; melanocytes showed a moderate neuronal nitric oxide synthase expression in white/lesional skin, demonstrating that metabolic function still goes on. The obtained data demonstrated that vitiligo lesions were characterized by modifications of nitric oxide synthase isoforms, thus confirming the hypothesis that nitric oxide imbalance is involved in vitiligo and supporting the idea that nitric oxide synthase inhibitors might be used as a possible therapeutic approach for the management of vitiligo.
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http://dx.doi.org/10.3390/ijms18122533DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5751136PMC
November 2017

A Connectomic Analysis of the Human Basal Ganglia Network.

Front Neuroanat 2017 26;11:85. Epub 2017 Sep 26.

IRCCS Centro Neurolesi "Bonino Pulejo", Messina, Italy.

The current model of basal ganglia circuits has been introduced almost two decades ago and has settled the basis for our understanding of basal ganglia physiology and movement disorders. Although many questions are yet to be answered, several efforts have been recently made to shed new light on basal ganglia function. The traditional concept of "direct" and "indirect" pathways, obtained from axonal tracing studies in non-human primates and post-mortem fiber dissection in the human brain, still retains a remarkable appeal but is somehow obsolete. Therefore, a better comprehension of human structural basal ganglia connectivity , in humans, is of uttermost importance given the involvement of these deep brain structures in many motor and non-motor functions as well as in the pathophysiology of several movement disorders. By using diffusion magnetic resonance imaging and tractography, we have recently challenged the traditional model of basal ganglia network by showing the possible existence, in the human brain, of cortico-pallidal, cortico-nigral projections, which could be mono- or polysynaptic, and an extensive subcortical network connecting the cerebellum and basal ganglia. Herein, we aimed at reconstructing the basal ganglia connectome providing a quantitative connectivity analysis of the reconstructed pathways. The present findings reinforce the idea of an intricate, not yet unraveled, network involving the cerebral cortex, basal ganglia, and cerebellum. Our findings may pave the way for a more comprehensive and holistic pathophysiological model of basal ganglia circuits.
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http://dx.doi.org/10.3389/fnana.2017.00085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5622993PMC
September 2017

The Neglected Cerebello-Limbic Pathways and Neuropsychological Features of the Cerebellum in Emotion.

Cerebellum 2018 Apr;17(2):243-246

Department of Biomedical, Dental Sciences and Morphological and Functional Images, University of Messina, 98125, Messina, Italy.

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http://dx.doi.org/10.1007/s12311-017-0884-3DOI Listing
April 2018

The Effect of Different Cleaning Protocols on Post Space: A SEM Study.

Int J Dent 2016 28;2016:1907124. Epub 2016 Sep 28.

Human Pathology Department, University of Messina, Messina, Italy.

. Purpose of the present paper is to analyze the efficiency of different post-space irrigation protocols. . 28 single rooted teeth were endodontically treated. After post-space preparation every sample was assigned to one of three experimental groups and to one control group. In each group different irrigation protocols were performed as follows: EDTA (Group A), 37% orthophosphoric acid (Group B), and EDTA + 37% orthophosphoric acid with ultrasounds activation (Group C). In the control group (Group D) the irrigate association was not activated by ultrasounds. Three zones (coronal, middle, and apical) of each sample were analyzed by using Scan Electron Microscopy (SEM) without any metallization procedures. The presence of smear layer on the canal surface was qualitatively evaluated by applying Serafino's score with values included between 0 and 2. . The results of the research showed how Group C recorded the better results (0.81 ± 0.72). Group A and Group B showed lower mean scores (1.06 ± 0.69 and 1.08 ± 0.77); Group D showed the lowest mean score of 1.30 ± 0.69. The SEM observation analysis demonstrated how the smear layer presence decreased in the crown-apical direction. . The different post-space treatments statistically determine significant differences on the dentinal surfaces cleansing. The absence of ultrasonic activation lowers the cleansing efficacy of endocanalar irrigants, showing sensible differences among each post-space zone.
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http://dx.doi.org/10.1155/2016/1907124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5059547PMC
September 2016

A Direct Cortico-Nigral Pathway as Revealed by Constrained Spherical Deconvolution Tractography in Humans.

Front Hum Neurosci 2016 26;10:374. Epub 2016 Jul 26.

Department of Biomedical, Dental Sciences and Morphological and Functional Images, University of MessinaMessina, Italy; IRCCS Centro Neurolesi "Bonino Pulejo"Messina, Italy.

Substantia nigra is an important neuronal structure, located in the ventral midbrain, that exerts a regulatory function within the basal ganglia circuitry through the nigro-striatal pathway. Although its subcortical connections are relatively well-known in human brain, little is known about its cortical connections. The existence of a direct cortico-nigral pathway has been demonstrated in rodents and primates but only hypothesized in humans. In this study, we aimed at evaluating cortical connections of substantia nigra in vivo in human brain by using probabilistic constrained spherical deconvolution (CSD) tractography on magnetic resonance diffusion weighted imaging data. We found that substantia nigra is connected with cerebral cortex as a whole, with the most representative connections involving prefrontal cortex, precentral and postcentral gyri and superior parietal lobule. These results may be relevant for the comprehension of the pathophysiology of several neurological disorders involving substantia nigra, such as parkinson's disease, schizophrenia, and pathological addictions.
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http://dx.doi.org/10.3389/fnhum.2016.00374DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4960230PMC
August 2016

Effect of bisphosphonates on the mandibular bone and gingival epithelium of rats without tooth extraction.

Exp Ther Med 2016 May 15;11(5):1678-1684. Epub 2016 Mar 15.

Department of Biomedical Sciences and Morpho-Functional Images, University of Messina, I-98125 Messina, Italy.

Osteonecrosis of the jaw (ONJ) is an adverse effect of bisphosphonate treatment that has become the subject of increasing investigations, in particular due to its poorly understood pathogenesis. Several experimental studies on animal models have been conducted; however, the majority of these replicate human ONJ following tooth extraction, and describe alterations in the bone and gingival epithelium when necrosis is manifested. The aim of the present study was to analyze the rat mandibular bone and gingival epithelium during 45 days of zoledronate treatment (which is a bisphosphonate agent), without tooth extraction. Intraperitoneal injections of zoledronate acid (0.1 mg/kg) were performed three times a week in normal male Wistar rats (n=20), while a control group of rats (n=20) was treated with saline solution for 45 days. After 7, 15, 30 and 45 days of drug treatment, all rats were sacrificed and hematoxilin and eosin staining, immunofluorescence and scanning electron microscopy analyses were performed. The results of the analyses after 7 and 15 days of treatment were similar in the treatment and control group. After 30 and 45 days of treatment, structural alterations were observed in the bone. No structural alterations to the gingival epithelium were observed. Based on these results, it was hypothesized that low doses of zoledronate act directly on the bone tissues to induce morphological alterations from bone to necrotic tissue following surgical procedures, although no cytotoxic effects were detected in the gingival epithelium.
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http://dx.doi.org/10.3892/etm.2016.3168DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4840833PMC
May 2016

In Vivo CT Direct Volume Rendering: A Three-Dimensional Anatomical Description of the Heart.

Pol J Radiol 2016 21;81:21-8. Epub 2016 Jan 21.

Department of Biomedical Sciences and Morphological and Functional Images, University of Messina, Messina, Italy; IRCCS Centro Neurolesi "Bonino Pulejo", Messina, Italy.

Background: Since cardiac anatomy continues to play an important role in the practice of medicine and in the development of medical devices, the study of the heart in three dimensions is particularly useful to understand its real structure, function and proper location in the body.

Material/methods: This study demonstrates a fine use of direct volume rendering, processing the data set images obtained by Computed Tomography (CT) of the heart of 5 subjects with age range between 18 and 42 years (2 male, 3 female), with no history of any overt cardiac disease. The cardiac structure in CT images was first extracted from the thorax by marking manually the regions of interest on the computer, and then it was stacked to create new volumetric data.

Results: The use of a specific algorithm allowed us to observe with a good perception of depth the heart and the skeleton of the thorax at the same time. Besides, in all examined subjects, it was possible to depict its structure and its position within the body and to study the integrity of papillary muscles, the fibrous tissue of cardiac valve and chordae tendineae and the course of coronary arteries.

Conclusions: Our results demonstrated that one of the greatest advantages of algorithmic modifications of direct volume rendering parameters is that this method provides much necessary information in a single radiologic study. It implies a better accuracy in the study of the heart, being complementary to other diagnostic methods and facilitating the therapeutic plans.
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http://dx.doi.org/10.12659/PJR.895476DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4727493PMC
February 2016

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

Hypertonic Saline in Conjunction with High-Dose Furosemide Improves Dose-Response Curves in Worsening Refractory Congestive Heart Failure.

Adv Ther 2015 Oct 31;32(10):971-82. Epub 2015 Oct 31.

Dipartimento Biomedico di Medicina Interna e Specialistica (DIBIMIS), AOUP "Paolo Giaccone" Università degli Studi di Palermo, Palermo, Italy.

Introduction: Diuretic responsiveness in patients with chronic heart failure (CHF) is better assessed by urine production per unit diuretic dose than by the absolute urine output or diuretic dose. Diuretic resistance arises over time when the plateau rate of sodium and water excretion is reached prior to optimal fluid elimination and may be overcome when hypertonic saline solution (HSS) is added to high doses of furosemide.

Methods: Forty-two consecutively hospitalized patients with refractory CHF were randomized in a 1:1:1 ratio to furosemide doses (125 mg, 250 mg, 500 mg) so that all patients received intravenous furosemide diluted in 150 ml of normal saline (0.9%) in the first step (0-24 h) and the same furosemide dose diluted in 150 ml of HSS (1.4%) in the next step (24-48 h) as to obtain 3 groups as follows: Fourteen patients receiving 125 mg (group 1), fourteen patients receiving 250 mg (group 2), and fourteen patients receiving 500 mg (group 3) of furosemide. Urine samples of all patients were collected at 30, 60, and 90 min, and 3, 4, 5, 6, 8, and 24 h after infusion. Diuresis, sodium excretion, osmolality, and furosemide concentration were evaluated for each urine sample.

Results: After randomization, 40 patients completed the study. Two patients, one in group 2 and one in group 3 dropped out. Patients in group 1 (125 mg furosemide) had a mean age of 77 ± 17 years, 43% were male, 6 (43%) had heart failure with a preserved ejection fraction (HFpEF), and 64% were in New York Heart Association (NYHA) class IV; the mean age of patients in group 2 (250 mg furosemide) was 80 ± 8.1 years, 15% were male, 5 (38%) had HFpEF, and 84% were in NYHA class IV; and the mean age of patients in group 3 (500 mg furosemide) was 73 ± 12 years, 54% were male, 6 (46%) had HFpEF, and 69% were in NYHA class IV. HSS added to furosemide increased total urine output, sodium excretion, urinary osmolality, and furosemide urine delivery in all patients and at all time points. The percentage increase was 18,14, and 14% for urine output; 29, 24, and 16% for total sodium excretion; 45, 34, and 20% for urinary osmolarity; and 27, 36, and 32% for total furosemide excretion in groups 1, 2, and 3, respectively. These findings were translated in an improvement in the furosemide dose-response curves in these patients.

Conclusion: These results may serve as new pathophysiological basis for HSS use in the treatment of refractory CHF.
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http://dx.doi.org/10.1007/s12325-015-0254-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4635178PMC
October 2015

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

Constrained spherical deconvolution analysis of the limbic network in human, with emphasis on a direct cerebello-limbic pathway.

Front Hum Neurosci 2014 8;8:987. Epub 2014 Dec 8.

Department of Biomedical Sciences and Morphological and Functional Images, University of Messina Messina, Italy ; IRCCS Centro Neurolesi Bonino Pulejo Messina, Italy.

The limbic system is part of an intricate network which is involved in several functions like memory and emotion. Traditionally the role of the cerebellum was considered mainly associated to motion control; however several evidences are raising about a role of the cerebellum in learning skills, emotions control, mnemonic and behavioral processes involving also connections with limbic system. In 15 normal subjects we studied limbic connections by probabilistic Constrained Spherical Deconvolution (CSD) tractography. The main result of our work was to prove for the first time in human brain the existence of a direct cerebello-limbic pathway which was previously hypothesized but never demonstrated. We also extended our analysis to the other limbic connections including cingulate fasciculus, inferior longitudinal fasciculus, uncinated fasciculus, anterior thalamic connections and fornix. Although these pathways have been already described in the tractographic literature we provided reconstruction, quantitative analysis and Fractional Anisotropy (FA) right-left symmetry comparison using probabilistic CSD tractography that is known to provide a potential improvement compared to previously used Diffusion Tensor Imaging (DTI) techniques. The demonstration of the existence of cerebello-limbic pathway could constitute an important step in the knowledge of the anatomic substrate of non-motor cerebellar functions. Finally the CSD statistical data about limbic connections in healthy subjects could be potentially useful in the diagnosis of pathological disorders damaging this system.
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http://dx.doi.org/10.3389/fnhum.2014.00987DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4259125PMC
December 2014