Evaluation of a large set of patients with Autoimmune Polyglandular Syndrome from a single reference centre in context of different classifications.

PURPOSE: To characterize patients with APS and to propose a new approach for their follow-up. Query ID="Q1" Text="Please check the given names and familynames." METHODS: Monocentric observational retrospective study enrolling patients referred to the Outpatients clinic of the Units of Endocrinology, Diabetology, Gastroenterology, Rheumatology and Clinical Immunology of our Hospital for Autoimmune diseases. RESULTS: Among 9852 patients, 1174 (11.9%) [869 (73.9%) female] were diagnosed with APS. In 254 subjects, the diagnosis was made at first clinical evaluation (Group 1), all the other patients were diagnosed with a mean latency of 11.3 ± 10.6 years (Group 2). Group 1 and 2 were comparable for age at diagnosis (35.7 ± 16.3 vs. 40.4 ± 16.6 yrs, p = .698), but different in male/female ratio (81/173 vs 226/696, p = .019). In Group 2, 50% of patients developed the syndrome within 8 years of follow-up. A significant difference was found after subdividing the first clinical manifestation into the different outpatient clinic to which they referred (8.7 ± 8.0 vs. 13.4 ± 11.6 vs. 19.8 ± 8.7 vs. 7.4 ± 8.1 for endocrine, diabetic, rheumatologic, and gastroenterological diseases, respectively, p < .001). CONCLUSIONS: We described a large series of patients affected by APS according to splitters and lumpers. We propose a flowchart tailored for each specialist outpatient clinic taking care of the patients. Finally, we recommend regular reproductive system assessment due to the non-negligible risk of developing premature ovarian failure.

SIMULTANEOUS INTAKE OF LIQUID L-T4 FORMULATION AND IRON SALT: FACT OR FICTION?

Context: Hypothyroidism and iron deficiency are among the most common pathologies in population. Therefore, there are a lot of patients assuming both iron salt supplements and levothyroxine therapy. Objective: To evaluate the effect of iron salt intake on L-T4 absorption among different L-T4 formulations. Materials and methods: A PubMed/MEDLINE, Web of Science, and Scopus research was performed. Original studies and reviews written in English and published online up to 21 December 2022 were selected and reviewed. The final reference list was defined based on the relevance of each paper to the scope of this review. Results: The data show an impaired absorption of L-T4 in tablets formulation when taken concomitantly with iron salt supplements. These phenomena seem to be circumvented by new L-T4 formulations. Conclusion: Liquid L-T4 formulations can be ingested with iron salts, with no impairment of absorption. More studies are necessary to confirm these data for soft-gel capsules L-T4.

Use of supercharged cover screw as static magnetic field generator for bone healing, 2nd part: in vivo enhancement of bone regeneration in rabbits.

In 1979, Pulsed electromagnetic fields (PEMFs) were approved by the Food and Drug Administration as an effective method in the treatment of non-unions. As well as PEMFs, also static magnetic fields (SMFs) have been widely investigated in orthopaedic studies. Even if the exact mechanism of action is not well understood, a large number of studies showed specific effects both at cellular and tissue levels. As bone fracture healing and osseointegration share the same biological events, the application of magnetic field stimulation in order to facilitate the osseointegration process has been suggested. In this study we investigated BIC and newly formed bone volume around dental implants inserted in the tibia of New Zealand rabbits after SMF stimulation, generated by a small-customized cover-screw-shaped neodymium-iron-bore magnet placed in the inner cavity of dental implants. As a result, we found that the SMF field generated around dental implants enhanced bone healing in the animal model. Our findings represent, to our knowledge, the first ready clinical technique for dental implants showing the ability of SMF to promote the osteogenesis process in vivo.

Use of supercharged cover screw as static magnetic field generator for bone healing, 1st part: in vitro enhancement of osteoblast-like cell differentiation.

Since 1979, Pulsed electromagnetic fields (PEMFs) have been approved by the Food and Drug Administration as an effective method in the treatment of non-unions. As well as PEMFs, also static magnetic fields (SMFs) have been widely investigated in orthopaedic studies. Even if the exact mechanism of action is not well understood, a large number of studies showed specific effects both at cellular and tissue levels. As bone fracture healing and osseointegration share the same biological events, the application of magnetic field stimulation in order to facilitate the osseointegration process has been suggested. In this study we investigated the proliferation rate and gene expression profile of MG63 osteoblastic-like cells after a 24, 48 and 72-hour SMF stimulation, generated by a small, customized cover screw-shaped neodymium-iron-bore magnet placed in the inner cavity of a dental implant. As a result, we found that the application of a SMF to osteoblastic-like cells does slightly decrease cell proliferation rate while enhancing the expression of those genes correlated to differentiation and mineralization. Our findings represent, to our knowledge, the first clinical ready technique for dental implants showing the ability of SMF to promote the osteogenesis process in vitro.

Osteopontin, osteocalcin and OB-cadherin expression in Synthetic nanohydroxyapatite vs bovine hydroxyapatite cultured Osteoblastic-like cells.

Calcium phosphate ceramics have been applied in bone replacement for several decades due to their excellent biocompatibility, bioactivity, osteo-conductivity and mechanical strength. Several studies have demonstrated that porous hydroxyapatite (HA) is an excellent scaffold for osteogenic proliferation and differentiation of the osteoprogenitor cells. However, different methods of synthesis and production of HA ceramic-based materials may have considerable effect on the physical and biological properties. In the present work, two hydroxyapatite-based materials, a natural hydroxyapatite ceramic of bovine origin and a synthetic nano-cristalline hydroxyapatite were tested in vitro with MG63 cell line. The results displayed that both the materials demonstrated a good biocompatibility. The immunocytochemical stain revealed a different positivity of the osteogenic markers between the cultures with the biomaterials, and the control culture. Western blot data confirmed the immunocytochemical stain. Both the materials tested in the present study demonstrated a good biocompatibility with the osteoblastic cells allowing, at the same time, the osteogenic differentiation, and they may be useful in clinical use.

Novel hydroxyapatite biomaterial covalently linked to raloxifene.

Since raloxifene, a drug used in osteoporosis therapy, inhibits osteoclast, but not osteoblast functions, it has been suggested to improve recovery during implant surgery. The present paper describes an effective method to link raloxifene, through a covalent bond, to a nano-Hydroxyapatite-based biomaterial by interfacing with (3-aminopropyl)-Triethoxysilane as assessed by Infra Red-Fourier Transformed (IR-FT) spectroscopy and Scanning Electron Microscope (SEM). To evaluate the safety of this modified new material, the vitality of osteoblast-like cells cultured with the new biomaterial was then investigated. Raloxifene-conjugated HAbiomaterial has been shown to be a safe material easy to obtain which could be an interesting starting point for the use of a new functional biomaterial suitable in bone regeneration procedures.

Pre-clinical evaluation of a new coral-based bone scaffold.

Coral is used worldwide for bone reconstruction. The favorable characteristics that make this material desirable for implantation are (i) osteoinduction, (ii) and osteoconduction. These proprieties have been demonstrated by in vivo studies with animal models and clinical trials over a twenty-year period. Also poly(2-hydroxyethylmethacrylate) [poly(HEMA)] is a widely used biomaterial. By using coral and poly(HEMA), a scaffold for bone reconstruction application has been recently synthesized. Cytological, histological and genetic analyses were performed to characterize this new alloplastic material. Four samples were analyzed: (a) white coral (WC), (b) red coral (RC), (c) WC plus polymer (WCP) and (d) RC plus polymer (RCP). Quantification of mitochondrial dehydrogenase activity by MTT assay was performed as indirect detector of cytotoxicity. In vivo effects were revealed by implanting corals and coral-based polymers in rabbit tibia. Samples were collected after 4 weeks and subjected to histological analysis. To evaluate the genetic response of cells to corals and coral-derived polymers an osteoblastlike cell line (i.e. MG63) was cultured in wells containing (a) medium, (b) medium plus corals and (c) medium plus two types of scaffolds (RCP or WCP). RNAs extracted from cells were retro-transcribed and hybridized on DNA 19.2K microarrays. No cytotoxicity was detected in corals and coral-based biopolymers. No inflammation or adverse effect was revealed by histological examination. By microarray analysis 154 clones were differentially expressed between RC and WC (81 up and 73 down regulated) whereas only 15 clones were repressed by the polymer. Histological evaluation not only confirmed that coral is a biocompatible material, but also that the polymer has no adverse effect. Microarray results were in agreement with cytological and histological analyses and provided further data regarding the genetic effects of RC, WC and the new polymer.

Expression of poly(ADP-ribose) polymerase in bone regeneration.

Poly(ADP-ribose) polymerase (PARP) is a 116kDa enzyme catalysing the synthesis of ADP-ribose polymers from NAD+. PARP is activated in response to DNA strand breaks and plays a critical role in the maintenance of genomic integrity. However, considering its role also in transcription, proliferation as well as apoptosis in biological process, in the present study the role of PARP in bone regeneration was evaluated, in particular in bone cell proliferation and differentiation processes. Thus, formalin fixed paraffin embedded specimens of 10 human bone samples after sinus lift were collected and investigated by immunohistochemistry using a mouse monoclonal anti-human PARP antibody. PARP was expressed in cells with morphological features of osteoblasts in the areas of new bone formation at the junction between mineralized and unmineralized tissue, between osteoid tissue and bone. Few osteoclasts were observed and showed only focal nuclear expression of PARP, while osteocytes showed no positivity for PARP. Our data showed an overall involvement of PARP enzyme in human bone tissues, in particular during bone regeneration process.

Trail overexpression inversely correlates with histological differentiation in intestinal-type sinonasal adenocarcinoma.

INTRODUCTION: Despite their histological resemblance to colorectal adenocarcinoma, there is some information about the molecular events involved in the pathogenesis of intestinal-type sinonasal adenocarcinomas (ITACs). To evaluate the possible role of TNF-related apoptosis-inducing ligand (TRAIL) gene defects in ITAC, by investigating the immunohistochemical expression of TRAIL gene product in a group of ethmoidal ITACs associated with occupational exposure. MATERIAL AND METHODS: Retrospective study on 23 patients with pathological diagnosis of primary ethmoidal ITAC. Representative formalin-fixed, paraffin-embedded block from each case was selected for immunohistochemical studies using the antibody against TRAIL. Clinicopathological data were also correlated with the staining results. RESULTS: The immunohistochemical examination demonstrated that poorly differentiated cases showed a higher percentage of TRAIL expressing cells compared to well-differentiated cases. No correlation was found with other clinicopathological parameters, including T, stage and relapses. CONCLUSION: The relationship between upregulation of TRAIL and poorly differentiated ethmoidal adenocarcinomas suggests that the mutation of this gene, in combination with additional genetic events, could play a role in the pathogenesis of ITAC.

SPECT analysis of a new implant surface: a human preliminary report.

AIM: Several recent medical reports have focused attention on the possible application of skeletal scintigraphy imaging in odontostomatology. The aim of the present report was to assess the influence of a new implant surface on peri-implant osteoblastic activity through bone scintigraphy. METHODS: Implants were placed in one healthy subject. A nuclear medicine investigation with single-photon emission-computed tomography (SPECT) was performed at 30 and 90 days after implant placement. The study was completed with acquisition of planar images of the skull in an anterior view and the use of regions of interest (ROIs) of the same size in the area corresponding to new surfaces implants and in the opposite maxilla (at the control sites). Count density ratios (counts/pixel) obtained from each ROI were used for a quantitative/relative assessment. Tomographic images were evaluated with a qualitative method. RESULTS: Routine planar methodology provided a direct measure of cellular activity of the examined areas. The difference in count density ratio registered from the same ROI between the first and the second scintigraphy revealed the course of peri-implant osteoblastic activity, which was very high in the first month and then declined during subsequent months. CONCLUSIONS: In spite of the small number of involved patients, the results obtained from this pilot study suggest that nuclear medicine investigation held advantages in oral implantology to clarify those aspects still unknown dealing with osteoblastic activity.

Adhesion and growth of osteoblast-like cells on laser-engineered porous titanium surface: expression and localization of N-cadherin and beta-catenin.

Response of different types of cells on biomaterials is crucial for the applications of tissue engineering and regenerative medicine. It is recognized that cell behaviour depends largely on material surface characteristics. The purpose of this study was to define the biologic response of MG63 cells to the innovative patented surface SYNTHEGRA. MG63 morphology and distribution on the three different titanium disk surfaces (sandblasted, smooth, and laser-treated) were evaluated by microscopy analysis after staining with hematoxylin and eosin. Cell adhesion was determined by crystal violet assay at 48 h while proliferation and cytotoxicity were performed by MTT assay at 24, 48, 72 and 240 h. The expression and localization of N-cadherin and beta-catenin were studied by immunofluorescence and confocal microscopy. At 48 h the adhesion was similar in all titanium surfaces, no difference in cell viability were observed in all titanium disks when compared with controls, while the cell growth on laser-treated disks was significantly higher at 240 h than at 24 and 72 h. Morphological analysis show that cells are aligned along the grooves and inside the cavities. beta-catenin signal appeared more diffuse and localized underneath the cell membrane, while N-cadherin signal was fainter in cells grown on SYNTHEGRA surface. This work put into evidence the performance of newly designed laser-micromachined surface for adhesion, growth and distribution of human osteoblast-like cells. SYNTHEGRA surface inducing modification of N-cadherin and beta-catenin expression and localization, are suggestive of cells undergoing differentiation towards osteocytes and could be particularly suited for immediate load implant procedures.

New perspectives in medical approach to therapy of head and neck squamous cell carcinoma.

Head and neck cancer is the eighth most common cause of cancer death worldwide. Its incidence varies widely among different regions. In North America and the European Union, head and neck cancer accounts for 3% to 4% of all cancer diagnoses. Conversely, in Southeast Asia and Africa, head and neck cancer accounts for approximately 8% to 10% of all cancers. Although the incidence of head and neck cancers has decreased slightly from 1975 to 2002 in the United States, approximately 46,000 new cases are still expected in 2007 alone. Even if surgery and radiotherapy have remained the core therapy in squamous cell carcinoma of the head and neck (HNSCC). Radiotherapy following surgery was the standard approach to the treatment of locoregionally advanced (LA-HNSCC) resectable disease. However, some recent developments highlighted the expanding role of chemotherapy, which is increasingly being incorporated in the management of HNSCC. Concurrent chemo-radiotherapy has shown benefits in randomized trials; in addition, chemotherapy is used by itself as palliative therapy for patients with metastatic disease. As our understanding of the molecular and cellular mechanisms involved in cancer development improves, we are better able to identify potential targets for biological therapy and to apply novel strategies to the preclinical study and clinical treatment of head and neck cancers. Current avenues of research, focusing on clinical studies evaluating antibody directed therapies and gene replacement strategies for head and neck cancer are discussed.

Raloxifene covalently bonded to titanium implants by interfacing with (3-aminopropyl)-triethoxysilane affects osteoblast-like cell gene expression.

Since Raloxifene, a drug used in osteoporosis therapy, inhibits the osteoclast functions but not osteoblast functions, it could improve the recovery during implant surgery. This preliminary report describes a simple method to link, through a covalent bond, Raloxifene to titanium by interfacing with (3-aminopropyl)-Triethoxysilane as assessed by the IR-FT and SEM. To evaluate the biological response of osteoblast-like cells to this implant, we compared expression gene profiling of cell cultures on Raloxifene conjugated implant and normal implant by DNA microarray. By using DNA microarrays containing 19,200 genes, we identified differently expressed genes in osteoblast-like cell line (MG-63). Surface Raloxifene conjugated implants have been shown to have a relevant importance in modifying cell response. This result could be an interesting starting point for the use of an immediate functional loading of implants.

Comparative analysis of direct and indirect implant impression techniques an in vitro study. An in vitro study.

Implant impression and transfer of the implant position to a working cast for rehabilitative purposes not always represent a predictable reconstructive step. The variable results depend on the transfer technique utilized and on the accuracy of the impression materials. The aim of this study was to compare the accuracy of the direct and indirect impression techniques and to analyze the distortion of different impression materials. An edentulous acrylic resin mandible was used as reference model: in the cuspid position 2 laboratory analogs were inserted perpendicularly to the occlusal plane and fastened with resin. Two impressions for each indirect and direct recording techniques with 4 different impression materials were made. Polyvinyl siloxanes were used for the repositioning implant level method. Polyethers were used for the ''pick up'' impression technique. Analysis of cast distortion was measured computing the inter-implant position on the developed models compared to that of the master model. Measurements were recorded by a digital caliper. The results of this in vitro study demonstrate that the direct impression technique is preferable to the indirect one and that the Impregum polyether impression material is the most precise when used in association with a direct technique.

Saliva as a diagnostic matrix for drug abuse.

Scientific interest in saliva as a diagnostic matrix has greatly increased over the last decade. The Triage screening test (Biosite Diagnostics), a rapid immunological test used to detect recreational drugs in the urine, was used to compare two biological matrixes: a non-conventional one, saliva, and a traditional one, urine. Twenty-one drug abusers collected one urine and one saliva specimen, both of which were tested with the Triage kit. Data were validated by gas-chromatography-mass-spectrometry (GC-MS). Results were positive for methadone in 9 saliva and 14 urine specimens, for opiates in 2 and 10, respectively, and for barbiturates in 2 specimens. Saliva specimens were negative for cannabis, THC, benzodiazepines and tricyclic antidepressants, although the GC-MS analysis revealed low concentrations of these drugs in the saliva. The study demonstrates the possibility of using saliva as a diagnostic matrix to test for drug-taking; however, the Triage kit must be improved before being used with saliva.

Comparative analysis of deformation of two implant/abutment connection systems during implant insertion. An in vitro study.

AIM: The implant/abutment interface represents a crucial element to maintain the structural stability of the implant restoration and to prevent mechanical problems that can compromise the long-term success of the implant treatment. METHODS: In this study deformation of the external hexagonal and internal octagonal extension of 2 implants after applying different values of insertion torque has been tested. The implants were secured in a customized resin baseplate, with the implant neck exposed, then different values of insertion torque were applied by an electronic torque controller. RESULTS: Five internal octagonal implants were tested for 60 seconds to different torque magnitudes (12 Ncm, 21 Ncm, 27 Ncm, 36 Ncm, 42 Ncm). Two external hexagonal implants were tested for 60 seconds to a torque value of 27 Ncm and of 36 Ncm. CONCLUSIONS: After torquing tests, each implant was examined by a scanning electron microscope (SEM) medium and high magnification to evaluate the deformation of the 2 different antirotational systems. The SEM analysis of the internal octagonal and external hexagonal antirotational systems of the TBR implant showed a deformation proportional to the magnitude of the applied torque during implant insertion. The geometric deformation of the antirotational extension is capable of compromising its function after a torque magnitude of 36 Ncm or superior to this value. Moreover it was demonstrated a more evident alteration of the external hexagonal extension in comparison with the octagonal system after applying a torque value of 27 Ncm.

[Teeth and oral mucosa in neurocutaneous syndromes, metabolic diseases and in diseases with defects of DNA repair]. / La mucosa orale e i denti in sindromi neurocutanee, malattie metaboliche e nelle malattie caratterizzate da difetti di riparo del DNA.

Oral mucosa is frequently involved in a group of genetic diseases, which affect the skin and other organs, particularly the central nervous system. The lesions may be of characterized by inflammations in neurocutaneous syndromes and by tumoral lesions in those diseases with defects of DNA repair. The teeth are mainly involved in progeria, while jaw keratocysts are highly characteristic in Gorlin's syndrome.

[Influence of biphosphonates on the integration process of endosseous implants evaluated using single photon emission computerized tomography (SPECT)]. / Valutazione scintigrafica con metodica SPECT dell'effetto dei bifosfonati sul processo di osseointegrazione implantare.

Biphosphonates are a large class of drugs which inhibits the resorbing activity of osteoclasts. The aim of this study was to evaluate the influence of topical application of the biphosphonate alendronate on the integration process of endosseus implants placed in a partially edentulous patient. After incision and elevation of a mucoperiosteal flap and carrying out the osteotomy, 2 SLA implants 10 mm long and 3.5 mm wide were inserted in the area of # 4.5 and 4.6. Before placement of # 4.5, a paste made of grinded tablets of alendronate and Rifocin was applied in the osteotomy. Fifteen days after stage I, an evaluation of the osteoblastic peri-implant activity was carried out using single photon emission computerized tomography. Healing was within normal limits. Four months after stage I, the 2 implants were uncovered and considered clinically and radiographically integrated. The osteoblastic activity was judged similar bet-ween the 2 implants in terms of quality of biological response. Osseous scintigraphy and the achievement of implant osseointegration demonstrate the lack of toxicity of the topical application of the biphosphonate alendronate during the initial osseous healing. However, new experimental studies and clinical trials are necessary to confirm the results obtained.

[Tooth and oral mucosa hereditary anomalies in complex syndromes characterized by hyper- or hypotrichosis]. / Anomalie ereditarie dei denti e della mucosa orale in sindromi complesse caratterizzate da iper o ipotricosi.

A wide range of hereditary anomalies, characterized by hair defects and only partially known from the genetics point of view, involves the teeth and oral mucosa with particular features. Teeth alterations are extremely heterogeneous; very frequently gums, palate, tongue and lips are affected. Waiting for a more comprehensive genetic definition and classification, these anomalies are grouped according to the hair defect (hypotrichosis, hypertrichosis and mixed-type).

[Vertical ridge augmentation using a microplate in conjunction with a Gore-Tex membrane. A case report]. / Aumento verticale della cresta alveolare mediante utilizzazione di una micropiastra in combinazione con una membrana barriera Gore-Tex. Tecnica chirurgica.

Oral implantology is considered an acceptable treatment modality to replace missing teeth when a recipient site with a sufficient horizontal and vertical bone volume exists. Guided bone regeneration is based on the principle of selective exclusion of non osteogenic cells from the bony defect by a barrier membrane. Several supporting systems of the barrier membrane have been successfully used to treat non space-mantaining de-fects. A 35-year-old female affected by a partial edentulism in the molar area of the right mandible showed 8 mm of bone height of the residual ridge above the alveolar canal. A vertical ridge augmentation was performed using a Gore-Tex membrane in conjunction with a microplate and an irradiated freeze-dried cortico-cancellous allograft. Six months after the surgical procedure a 11.5 mm by 5 mm threaded implant was placed into the regenerated bone. After three months of healing, the implant was uncovered and considered integrated. Before the implant placement, a biopsy of the regenerated bone was arried out by a triphine. The histological examination of the bony core showed the attainment of biological goals of guided bone regeneration. The surgical technique followes in this case report has been effective in regenerating a vertical bone volume sufficient for implant treatment.