bluuebunny/crossref_metadata_2025 huggingface dataset:
Clodronate Combined with a Surfactant (Tween 20) Does Not Improve Osseointegration: A Rabbit Immunohistomorphometric Study
Authors: Berardi D. , Raffaelli L. , Perfetti G. , Paolantonio M. , Trisi P.
Published: January 2017

Biphosphonates are compounds that inhibit bone reabsorption mediated by osteoclasts or the progression of periodontal disease independent on the host response to pathogenic bacteria that colonize the tooth surface. The use of biphosphonates in oral implantology is still in the experimental stage. The aim of this study is to evaluate the efficacy of a non-aminobiphosphonate combined with a surfactant to increase the ability of the drug to link to the implant and bone surfaces in the development of osseointegration in rabbits. Smooth titanium implants were devised to be used on rabbit femurs. A topical administration of clodronate combined with the surfactant (Tween 20) at different concentrations was made on the implant surface and in the implant site to increase the bone and implant adhesiveness. Placebo was given to the control group. New Zealand rabbits were used and sacrificed by CO2 after 8 weeks from the implantations. A histologic and histo-morphometric analysis was carried out. Results did not show significant difference between the tests and the placebo groups. Our data are different from other similar studies obtaining statistically significant differences. These differences could depend on the efficacy of the drug used and on the procedure of application of the drug on the implant. This study demonstrates poor efficacy of clodronate applied topically to the implant and implant site during surgery to increase the percentage of osseointegration in the implant. Further studies using different fixation techniques of the drug may be necessary to confirm the present data.
Allergy to Nickel: First Results on Patients Administered with an Oral Hyposensitization Therapy
Authors: Tammaro A. , De Marco G. , Persechino S. , Narcisi A. , Camplone G.
Published: January 2017

Nickel sulphate allergy is the most common contact allergy. In fact, nickel sulphate is an ubiquitous element, contained in various objects and food; it occurs in igneous rocks, as a free metal and together with iron, but it is also a component of living organism, mainly vegetables. We carried out a clinical trial of oral hyposensitization therapy with low doses of nickel in a group of 67 patients affected by systemic allergy to this sensitizer element. We obtained good results on consequent tolerance to nickel in treated patients.
Ivabradine Use in Refractory Unstable Angina: A Case Report
Authors: Ripa C. , Germano G. , Caparra A. , Capparuccia CA. , Antonicelli R.
Published: January 2017

In this report, we describe the clinical results of ivabradine use in a patient with a serious form of unstable angina. For this patient, it was proposed that no other therapeutic, pharmacologic or surgical, option was available. The patient is a 75-year-old woman who presented with repeated episodes of retrosternal chest pain. She notably had a history of type II diabetes mellitus treated by insulin for several years and complicated by diabetic macro-angiopathy. ECG tracings recorded during these episodes showed abnormalities of the lateral repolarization phase of ischaemic nature. There was no measured increase in cardiac enzymes. She was transferred to our CCU with a diagnosis of unstable angina. In our CCU, the patient was treated with nitrates, metoprolol, aspirin, clopidogrel and atorvastatin at maximal sustainable doses. Following persistent clinical-instrumental instability, she was subjected to coronary angiography. This study revealed severe multi-vessel coronary artery disease not amenable to surgery or angioplasty revascularization. In addition to the therapy already provided, a beta-blocker (metoprolol 50 mg x 2/die) and diltiazem (30 mg x 2/die) were added despite their potentially dangerous and adverse chronotropic effects. Despite this treatment, the patient's heart rate remained high (between 80 and 100 beats/min). This heart rate appeared to be the main driving cause of her anginal symptoms. At this point, the use of ivabradine seemed the only option, even though use would be ‘off-label’ compared to current indications for the drug's use. We started with a low dose of 2.5 mg/b.i.d. and titrated up to 5 mg b.i.d. As we titrated, we witnessed a gradual reduction in heart rate. A consequent stabilization of her clinical pattern progressed into an almost unexpected asymptomatic state. After about a week of clinical observation, the patient recovered. After three months, she remains asymptomatic.
Balance and Posture in the Elderly: An Analysis of a Sensorimotor Rehabilitation Protocol
Authors: Bellomo R.G. , Iodice P. , Savoia V. , Saggini A. , Vermiglio G. , Saggini R.
Published: January 2017

Regular training programs are a concrete means to prevent and/or reduce functional decline due to aging. A multisensory training approach seems to obtain better results in the elderly with regard to both balance and quality of life. Forty subjects (age 65±10 years, height 165±4 cm, weight 73.0±4.6 kg) were randomized into two groups (GrHu and GrCl). Participants in the GrHu group received 3 months of balance and postural training, 3 sessions per week, with the use of a multisensory training approach. Those in the GrCl group received 3 months of training with a classical rehabilitation protocol that included isotonic training for the lower limbs and spine. With regard to walking, there was an improvement in step symmetry for participants in the GrHu group compared to baseline (0.93±0.09 vs. 0.84±0.1; p<0.05). Further, all subjects in the GrHu group showed a significant reduction in the energy used during a 4-min walk. Analysis of stabilometry data also showed a significant improvement in balance for those in the GrHu group, which was independent of age or gender. The multisensory training approach yields an improvement of balance in the elderly, which reduces the risk of falls. The observed improvement is significantly greater than that seen with the classical training program.
Study of ABCB1 Multidrug Resistance Protein in a Common Orofacial Malformation
Authors: Martinelli M. , Carinci F. , Morselli P.G. , Palmieri A. , Girardi A. , Farinella F. , Baciliero U. , Scapoli L.
Published: January 2017

The onset of embryonic malformations is greatly determined by the intrauterine environment, conditioned by maternal lifestyle, diet, drugs and medication intake, in addition to both foetal and maternal genotypes. Maternal C677T MTHFR genotype has been identified as important factor in cleft lip with or without cleft palate (CL/P) etiology. In the present study we evaluated the possible interaction between maternal methylenetetrahydrofolate reductase (MTHFR) and foetal ABCB1 genotypes. ABCB1 gene codes for a drug-transport pump in charge to protect the cell by extruding a variety of harmful exogens, but with a reduced activity in a folate-restricted condition. Maternal 677T genotype is translated in a reduced folate availability for the developing embryo who consequently may becomes more exposed to external insults. A family based association analysis was performed to test the effect of ABCB1 polymorphisms in clefting, in the whole sample and in the stratified sample accordingly to maternal MTHFR genotype. No evidence of association between ABCB1 polymorphisms and CL/P was detected. This suggests that ABCB1 or ABCB1-MTHFR feto-maternal interaction could have no effect in orofacial clefting or could play a role in a limited number of cases.
Study of the 12q13 Region in Nonsyndromic Cleft Lip with or without Cleft Palate
Authors: Martinelli M. , Carinci F. , Morselli P.G. , Palmieri A. , Girardi A. , Clauser L. , Spinelli G. , Scapoli L.
Published: January 2017

The 12q13 region has been suggested as a candidate locus for orofacial cleft by different investigators. In the present study we tested the region for linkage with non syndromic cleft lip with or without cleft palate in a collection of 39 Italian multigenerational families, using microsatellite markers. No evidence of linkage was detected between the marker map and NSCLP under different mode of inheritance nor with a nonparametric method. Formal level of linkage exclusion, were obtained for each point of the map. Genetic heterogeneity and the different impact of the candidate locus among populations could explain conflicting results obtained in different studies.
Histomorphic-Metric Evaluation of an Immediately Loaded Implant Retrieved from Human Mandible after 2 Years
Authors: Traini T. , Danza M. , Zollino I. , Altavilla R. , Lucchese A. , Sollazzo V. , Trapella G. , Brunelli G. , Carinci F.
Published: January 2017

The aim of the present study was to evaluate the interplay between microstructure and function of the bone around an immediately loaded implant retrieved from human maxilla after 23 months due to fracture. A spiral implant of 3.3 mm x 15 mm was placed in a male 53 years old in the anterior region of the mandible bone (4.1) and it was processed for histology. The specimen was analyzed under the confocal scanning laser microscope (CSLM) and brightfield light microscope (LM) equipped with circularly polarized light (CPL). The BIC rate was 76.7± 4.9 (mean ±SD). Many cement lines indicates an high remodeling rate of the bone. The transverse collagen fiber orientation (CFO) (mean ±SD) under the lower flank of the thread near the tread tip was 55.2 ± 4.8 × 104 pixel while the longitudinal CFO was 45.8 ± 2.3 × 104 pixel (P<.05). In the inter-threads region the transverse CFO (mean ±SD) was 36.4 ± 2.4 × 104 pixel while the longitudinal CFO was 65.6 ± 6.5 × 104 pixel (P<.05). The osteocytes numbers (mean ±SD) was 205 ± 45 in the peri-implant bone and 144 ± 53 in the native bone (P=.007). After 2-years of loading the SLA spiral implant was well osseointegrated but still surrounded by woven bone. The osteocytes density was significantly higher in the peri-implant bone than in the native bone. The transverse collagen fibers were significantly associated with the lower flank of the implant threads, while the longitudinal collagen fibers were more represented in the straight surface of the implant. The implant fracture was correlated to crestal bone resorbing and subsequent fatigue yielding.
Detection of IDH1 Mutations and the Status of MGMT Promoter on Intraoperative Fresh Tissue Section from Frameless Neuronavigation Needle Biopsy. Analysis on 17 Patients with Brain Glial Tumor Ineligible for Craniotomy and Tumor Resection
Authors: Iaccarino C. , Nicoli D. , Serra S. , Froio E. , Pisanello A. , De Berti G. , Ghadirpour R. , Marcello N. , Servadei F. , Carinci F.
Published: January 2017

It is well known that primary and secondary glioblastomas are histologically largely indistinguishable. Therefore, the detection of IDH1 mutations or the status of the MGMT promoter on a simple bioptic sample could be one of major diagnostic and prognostic importance for glial patients that complements clinical criteria for distinguishing secondary from primary glioblastomas and to predict a more favorable prognosis. Currently, biopsy is the method of choice to obtain tissue from intracranial lesions with uncertain neurodiagnostic findings or in deep locations, with a minimal invasive approach. The needle biopsy with frameless neuronavigation could provide a sampling with elevated diagnostic yield and high concentration of DNA, due to the “image-guided” computer assisted technique of needle insertion through the most neurodiagnostic representative tumoral area. The freezing of fresh tumor tissue at biopsy could greatly improve the success of DNA extraction. The concentration of the DNA samples can also improved from a withdrawal in an area with high probability of neoplastic cells. The present study reports the results of 17 patients who had undergone frameless image-guided intracranial needle biopsy from April 2008 until July 2010 at Neurosurgery Unit of the “Arcispedale Santa Maria Nuova” of Reggio Emilia. For these patients the molecular determination of MGMT promoter was assessed with the Nested-Methylation Specific-Polymerase Chain Reaction and the screening of mutations in IDH1 e IDH2 genes was performer by polymerase chain reaction (PCR) and direct sequencing on fresh or cryopreserved needle bioptic tissue.
Calcium Sulfate Stimulates Pulp Stem Cells towards Osteoblasts Differentiation
Authors: Sollazzo V. , Lucchese A. , Palmieri A. , Carnevali G. , Iaccarino C. , Zollino I. , Della Valle M. , Pezzetti F. , Brunelli G. , Carinci F.
Published: January 2017

Calcium sulfate (CaS) is a highly biocompatible material and enhances bone formation in vivo. However, how CaS alters osteoblast activity to promote bone formation is poorly understood. To study how CaS can induce osteoblast differentiation in mesenchymal stem cells, the expression levels of bone related genes and mesenchymal stem cells marker were compared in normal osteoblasts and dental pulp stem cells, using real time Reverse Transcription-Polymerase Chain Reaction. Gene differentially expressed between the two cells type were the trascriptional factor RUNX2, osteopontin (SPP1), COL1A1 (collagen type 1α1) and alkaline phosphatase (ALPL). The obtained results demonstrated that CaS strongly influences the behavior of DPSCs in vitro enhancing proliferation, differentiation and deposition of matrix.
Expansion of the Alveolar Bone Crest with Ultrasonic Surgery Device: Clinical Study in Mandible
Authors: Scarano A. , Murmura G. , Sinjiari B. , Assenza B. , Sollazzo V. , Spinelli G. , Carinci F.
Published: January 2017

The purpose of this paper was to document the application to the split-crest mandibular procedure in two stage in order to avoid cortical resorption due to periosteal detachment in buccal cortical bone of the alveolar crest. Twenty-two healthy patients with non-contributory past medical history (14 women and 8 men, all non-smokers, mean age 59 years, range 54–65 years) were included in this study. After buccal mucoperiosteal flap was followed by a sagittal corticotomy in the coronal area of the alveolar crest and a second sagittal corticotomy, but in a lower (basal) position and two vertical corticotomies in the buccal wall, using a ultrasonic surgery device (Surgysonic, Esacrom, Imola Italy). Adequate crest expansion was achieved without compromising cortical vascularisation by utilising a combination of scalpel, thin chisels and threaded osteotomes (Bone System, Milano, Italy). Postoperative results were assessed by panoramic and periapical radiographs. Ossification of the osteotomy lines was evident and could be observed as sites with increasing radiopacity on panoramic and periapical radiographs 3 months after implants insertion. No dehiscence of the mucosa was observed. No patient suffered from hypoaesthesia. The mean horizontal bone increase in coronal area was 5±3 mm. Mandibular ridge expansion using a split-crest technique that included grafting the implant sites with a ultrasonic surgery device is a viable therapeutic alternative for implant placement in this patient population.
Analysis and Structural Examination of Screw Loosening in Oral Implants
Authors: Scarano A. , Murmura G. , Sinjiari B. , Sollazzo V. , Spinelli G. , Carinci F.
Published: January 2017

Biological and technical failures of implants have already been reported. Mechanical factors are certainly of importance in implant failures, even if their exact nature has not yet been established. The abutment screw fracture or loosening represents a rare, but quite unpleasant failure. The aim of the present research is an analysis and structural examination of screw thread or abutment. In this study broken screws were excluded. A total of 58 screw thread loosening were observed, 5 Branemark, (Nobel Biocare, Gothenburg, Sweden) 4 Implant Innovation (Riverside Drive Palm Beach Gardens, FL, USA) and 7 Restore (Lifecore Biomedical, Chaska, Minnesota, USA) and 42 T.B.R. implant (Benax, Ancona, Italy). The loosened abutment screws were retrieved and analyzed under SEM. Many alterations and deformations were present in concavities and convexities of screw threads.
Incidence of Low Risk Human Papillomavirus in Oral Cancer: A Real Time PCR Study on 278 Patients
Authors: Palmieri A. , Scapoli L. , Martinelli M. , Pezzetti F. , Girardi A. , Spinelli G. , Lucchese A. , Carinci F.
Published: January 2017

Squamous cell carcinoma is the most frequent malignant tumour of the oral cavity. It is widely known that tobacco and alcohol consumption are the major causes of the development of oral squamous cell carcinoma (OSCC). The human papilloma virus infection has also been postulated as a risk factor for squamous cell carcinoma, although conflicting results have been reported. The aim of this study is to evaluate the presence of high-risk and low-risk type human papillomavirus in a large sample of squamous cell carcinoma limited to the oral cavity by means of quantitative real-time polymerase chain reaction. Data were obtained from 278 squamous cell carcinoma limited to oral cavity proper. Sequencing revealed that 5 samples were positive for HPV type 16, 5 for HPV type 11, and 1 for HPV type 6. Human papillomavirus 11 was detected in 5 tumours out of the 278 examined. The prevalence rate for Human papillomavirus 11 was 1.8% (C.I. 0.7–3.9). The matched case-controls analysis indicated that the prevalence among controls did not significantly differ with respect to cases and that Human papillomavirus 11 alone did not correlate with squamous cell carcinoma.
Loh at PDCD4, CTNNB1, and CASP4 LOCI Contributes to Stage Progression of Oral Cancer
Authors: Scapoli L. , Girardi A. , Rubini C. , Martinelli M. , Spinelli G. , Palmieri A. , Muzio L. Lo , Carinci F.
Published: January 2017

Squamous cell carcinoma is the most frequent malignant tumor of the oral cavity. Markers of tumor progression that could help to define diagnosis, plan treatment and implement prognosis have still to be identified. Seven candidate markers for tumor progression were investigated using a loss of heterozygosity (LOH) assay. The sample was made up of 51 squamous cell carcinoma and adjacent normal tissues from the same patients. LOH at one, or more, markers was a relatively frequent event that was observed in 53% of tumors. The number of losses detected in each tumor was significantly associated with tumor severity. Significant association between UICC stage grouping and LOH was found for 3 gene loci: programmed cell death 4 (PDCD4), catenin beta 1 (CTNNB1), and caspase 4 (CASP4). No association between allelic loss and the occurrence of lymph node metastasis was found for any of the seven investigated loci. Overall, LOH contributes to tumor progression of oral SCC. A specific role for PDCD4, CTNNB1, and CASP4 was found.
Expression of β-Catenin and γ-Catenin in Maxillary Bone Regeneration
Authors: Santarelli A. , Colella G. , Carinci F. , Pannone G. , Rubini R. , Lo Russo L. , Polimeni A. , Sgaramella N. , Annibali S. , Spinelli G. , Lo Muzio L.
Published: January 2017

β- and γ-catenin are components of catenin family involved in cadherin adhesion function. Recently it has been shown that this family is involved in other functions such as signaling and activation of transcription factors. The final goal of this study was to evaluate the role of β- and γ-catenin in bone cell physiology and bone regeneration. Formalin-fixed-paraffin embedded specimens of 15 human bone specimens after sinus lift were collected and examined by immunohistochemstry using primary antibodies against β- and γ-catenin. Staining intensity and cellular localization were evaluated. β and γ-catenin showed a very high level of expression in human bone tissues. In particular catenins were expressed in cells with morphological findings of osteoblasts in the areas of new bone formation at the junction between mineralized and unmineralized tissue, between osteoid matrix and bone. Osteoclasts showed also positivity for catenins. Osteocytes, cells located in lacunae of mature mineralized bone with function of bone vitality maintenance, showed no expression for catenins. Specimens characterized by high amount of catenins in osteoblasts at 1° month showed high grade of bone maturation at 3° month. Data demonstrated an overall involvement of catenins in human bone tissues and in particular during bone regeneration process. The presence of staining for β- and γ-catenin particularly in osteoblasts demonstrates a significant role of catenins in functions, other than in cadherin interaction, such as signaling and activation of transcription factors during differentiation of bone tissues.
Expression of Sexual Hormones Receptors in Oral Squamous Cell Carcinoma
Authors: Colella G. , Izzo G. , Carinci F. , Campisi G. , Lo Muzio L. , D'Amato S. , Mazzotta M. , Cannavale R. , Ferrara D. , Minucci S.
Published: January 2017

Sexual hormones play an important role in expression of genes involved in a wide variety of biological and neoplastic processes. The information on Estrogen Receptors (ER) expression in non-target tissues is very few and, in particular, the studies in head and neck tumors are still controversial. Recent studies analyzed the role of Tamoxifen (TAM) on Oral Squamous Cell Carcinoma (OSCC) lines in relation to the presence/absence of ER. The purpose of the present study was to evaluate the expression of sexual hormones receptors mRNAs, in particular Estrogen Receptor alpha (ERα) and Androgen Receptor (AR) mRNA in OSCC tissues. The study group comprised 20 samples of OSCC, harvested from 20 otherwise healthy subjects (14 males and 6 females, mean age 58.2y, range 38–74). The control group was formed by 20 samples of normal mucosa harvested around the margins of the specimens (at least 1 cm from the lesion margins). Estrogens Receptor alpha (Era) and Androgen Receptor (AR) mRNA expressions were analyzed by RT-PCR carried out on total RNAs extracted from both cancerous and healthy tissues. Obtained data were evaluated by Shapiro-Walk normality test and compared by Student's t test. Results with p<0.05 were considered statistically significant. AR transcripts were less expressed in OSCC specimens than in healthy tissues, while levels of ERα transcripts significantly increased in tumor samples. These preliminary data show different expression patterns of AR and ERa mRNAs in malignant tissues of oral mucosa and could suggest an involvement of these sexual hormones in oral cancer.
Perioperative Period: Immunological Modifications
Authors: Cardinale F. , Chinellato I. , Caimmi S. , Peroni D.G. , Franceschini F. , Del Giudice M. Miraglia , Bernardini R.
Published: January 2017

Surgical stress induces complex modifications in the hemodynamic, metabolic, neuro-hormonal and immune response of the individual. The magnitude of these alterations depends on preoperative events leading to surgery, the severity of surgical trauma, and also on post-operative/post-traumatic complications (“multiple hit hypothesis”). As in other conditions of tissue damage, surgery trauma is followed by an immune-inflammatory response, initiated at the site of injury by the innate immune system, followed by a compensatory anti-inflammatory (or immunosuppressive) response (CARS), involving mainly cells of the adaptive immune system, which predispose the host to septic complications. The up-regulated inflammatory response, together with a profound impairment of macrophage and cell-mediated immunity, appear to be the cause for patients' increased susceptibility in developing subsequent sepsis after major surgery.
Perioperative Latex Allergy
Authors: Bernardini R. , Catania P. , Caffarelli C. , Cardinale F. , Franceschini F. , Pelosi U. , Peroni D.G.
Published: January 2017

The prevalence of latex allergy varies greatly depending on the population studied and the methods used to detect sensitization. Subjects considered to be at high risk for latex allergy are rubber industry workers, children with spina bifida and urological abnormalities, children undergoing multiple surgical procedures and with urinary catheterization, health care workers and people with food allergy (latex fruit syndrome). In this paper we report a review of latex proteins, the symptoms of latex allergy, diagnosis and management in subjects with latex allergy.
Perioperative Allergy: Therapy
Authors: Pajno G.B. , Crisafulli G. , Caminiti L. , Marseglia G.L. , Cardinale F. , Paravati F. , Caffarelli C.
Published: January 2017

Perioperative allergic reactions manifest in various ways. The majority of systemic reactions occur during anesthesia within minutes of intravenous induction; however, agents which are administered via other routes may cause reactions after more than 15 minutes. Anaphylaxis during anesthesia may present in many different ways and the signs and symptoms, which do not vary from those of anaphylactic reactions in general, may be masked by hypovolemia, light, deep anesthesia or extensive regional blockade. Recommendations for treatment are based on available evidence in the literature. A treatment algorithm is suggested, with emphasis on the incremental titration of adrenaline and fluid therapy as first-line treatment. Increased focus on this subject will hopefully lead to prompt diagnosis and rapid, correct treatment.
Scaffolds Combined with Stem Cells and Growth Factors in Healing of Pseudotumoral Lesions of Bone
Authors: De Biase P. , Campanacci D.A. , Beltrami G. , Scoccianti G. , Ciampalini L. , Pecchioli O. , Capanna R.
Published: January 2017

Reconstructions of large lesions or defects often require a bone graft or a bone substitute to promote healing. In common practice the reconstruction of a bone defect is dependent on the site and size of the lesion: in long bones intercalary defects may be managed with Ilizarov technique of bone transport and distraction osteogenesis or the use of a free or pedicled vascularized bone graft, or with Masquelet technique. For cavitary defects the available surgical options include autograft, allograft or xenograft or the use of synthetic scaffolds to promote bone regeneration. In order to promote a faster bone healing tissue engineering proposed the application of enriched graft to fill bone defects. The employment of enriched bone graft has been our choice in the last years to fill contained defects following curettage of a pseudotumoral lesion of bone. We report our clinical experience in terms of safety and success of these procedures at a long-term follow up.
Osgood Schlatter Lesion: Histologic Features of Slipped Anterior Tibial Tubercle
Authors: Falciglia F. , Giordano M. , Aulisa A.G. , Poggiaroni A. , Guzzanti V.
Published: January 2017

No study reports the histological features of the various zone of the anterior tubercle of the tibia in the different stages of the Osgood-Schlatter (O-S) lesion. For this reason we carried on an histological study. Specimens were taken from 13 patients with O-S lesion prior to surgery. In 4 cases in the apophyseal stage lesions were present in an altered fibrocartilage anterior to the ossification centre. In 9 cases in the epiphyseal stage varying degrees of reparative tissues were observed in the bed of the fragment of the secondary ossification centre. In 3 of them a zone of lesion was observed within the fibrocartilage anterior to the ossification centre. These results suggest that the slippage of the patellar tendon insertion may be progressive and caused by pathological fibrocartilage.
Regulatory Functions of Insulin-like Growth Factor Binding Proteins in Osteoarthritis
Authors: Galasso O. , De Gori M. , Nocera A. , Brunetti A. , Gasparini G.
Published: January 2017

Insulin-like growth factor binding proteins (IGFBPs) are a group of secreted proteins, which bind to IGF-I (and IGF-II) with high affinity and modulate the biological actions of IGFs. Abundant evidence points the importance of the IGF-I/IGFBP system on both cell growth and differentiation. A role for the IGF-I/IGFBP system in the regulation of normal human cartilage has been previously reported. In this context, recent studies suggest an emerging role for IGFBPs in the failure of cartilage during osteoarthritis (OA). Indeed, increased IGFBP levels have been reported in both the articular cartilage and synovial fluid from patients with OA. Overexpression of IGFBPs, by altering the bioavailability and function of IGFs, is likely to deliver IGFs-independent signals for chondrocyte survival. This, at least in part, might explain the degenerative changes of the cartilage in OA. Further studies are necessary to clarify the mechanisms that cause the overexpression of IGFBPs in patients with OA. Advances in our understanding of the relationship between osteoarthritis and the IGF-I/IGFBP system may lead to new treatment strategies for this degenerative disease.
Use of Collagen Scaffold and Autologous Bone Marrow Concentrate as a One-Step Cartilage Repair in the Knee: Histological Results of Second-Look Biopsies at 1 Year Follow-up
Authors: Gigante A. , Calcagno S. , Cecconi S. , Ramazzotti D. , Manzotti S. , Enea D.
Published: January 2017

Chondral articular defects are a key concern in orthopaedic surgery. To overcome the disadvantages of autologous chondrocyte implantation (ACI) and to improve the outcomes of autologous matrix-induced chondrogenesis (AMIC), the latter technique is currently augmented with bone marrow concentrate injected under or seeded onto the scaffold. However, to date, only a little is known about histological outcomes of either the AMIC technique or AMIC associated with bone marrow concentrate. This study aimed to evaluate the quality of the repair tissue obtained from biopsies harvested during second-look arthroscopy after arthroscopic AMIC augmented with bone marrow concentrate. We analysed five second-look core biopsies harvested at 12 months follow-up. At the time of biopsy the surgeon reported the quality of the repair tissue using the standard ICRS Cartilage Repair Assessment (CRA). Every biopsy together with patient data was sent to our centre to undergo blind histological evaluation (ICRS II Visual Histological Assessment Scale) and data analysis. Five asymptomatic patients (mean age 43.4 years) had isolated lesions (mean size was 3.7 cm2) at the medial femoral condyle. All the implants appeared nearly normal (ICRS CRA) at arthroscopic evaluation and had a mean overall histological (ICRS II) of 59.8 ±14,5. Hyaline-like matrix was found in only one case, a mixture of hyaline/fibrocartilage was found in one case and fibrocartilage was found three cases. Our clinical and histological data suggest that this procedure achieved a nearly normal arthroscopic appearance and a satisfactory repair tissue, which was possibly still maturing at 12 months follow-up. Further studies are needed to understand the true potential of one-step procedures in the repair of focal chondral lesions in the knee.
Histological and Ultrastructural Reaction to Different Materials for Orthopaedic Application
Authors: Del Bravo V. , Graci C. , Spinelli M.S. , Muratori F. , Maccauro G.
Published: January 2017

Prosthetic joints loosening in absence of infection is the most common reason for revision surgery and is known as aseptic loosening. A significant role in the pathogenesis of implant failure undoubtedly played by the generation of wear debris, mainly from the load bearing joint surfaces, and the cellular reaction through the formation of tissue membrane around implants. This article analyzes histologic, immunohistochemical ad ultrastructural aspects of periprosthetic tissue membrane collected at time of surgical revision, paying attention on cell host response to different materials: metals, polyethylene and ceramics. Dimension of particles seems to be crucial in the activation of different cell population to wear debris.
Local Adjuvants in Surgical Management of Bone Metastases
Authors: Piccioli A. , Ventura A. , Maccauro G. , Spinelli M.S. , Del Bravo V. , Rosa M. A.
Published: January 2017

Curettage is one of the most common method for surgical treatment of bone metastasis. Local adjuvant improve most commonly used for improving the effect of curettage in local cancer surgery may exerted their effects either chemically either physically; in Orthopedic Oncology the most common are phenol, liquid nitrogen, laser, and cement. This article reviewed the main characteristics of the most common chemical and physical agents used in bone oncology, emphasizing the toxic effects of some of them, especially phenol and liquid nitrogen.
Zirconia Toughened Alumina (ZTA) Powders: Ultrastructural and Histological Analysis
Authors: Spinelli M.S. , Maccauro G. , Graci C. , Cittadini A. , Magnani G. , Sangiorgi S. , Del Bravo V. , Manicone Pf , Raffaelli L. , Muratori F. , Sgambato A.
Published: January 2017

Ceramic materials, as Alumina and Zirconia, has made an improvement in the choice of new biomaterials for the load bearing application in dental and orthopaedic implants. These materials has shown mechanical resistance to high stress related to weight bearing and low debris in time. For this reason they are indicated on young patients implant, with high demanding activities and long life expectance. In literature however the risk of chronic inflammation due to chronic wear debris release and the possibility of carcinogenesis, is still to be definitively investigated. Another point to investigate is the acute reaction of the tissue in case of acute release of powders of these materials. The aim of this study was to investigate the possible local and systemic acute effects of ceramic precursors in form of powders of different size when released into articular joint. Powders of ZTA were implanted in the knee joint of twenty-four New Zealand white adult rabbits, that were sacrificed at 1,3,6, and 12 months. Radiographic, histological and immunoistochemestry analysis were conducted on periprosthetic tissue and peripheral organs, to verifying local host response and systemic toxic effects.
Orthopaedic Research in Italy: State of the Art
Authors: Cenni E. , Scioscia L. , Baldini N.
Published: January 2017

The most significant results in experimental and clinical orthopaedic research in Italy within the last three years have been primarily in major congenital diseases, bone tumors, regenerative medicine, joint replacements, spine, tendons and ligaments. The data presented in the following discussion is comparable with leading international results, highlighting Italian orthopaedic research excellemce as well as its shortcomings.
Impact of Different Concentrations of Human Recombinant Growth Hormone on T Lymphocytes
Authors: Borrione P. , Grasso L. , Pautasso M. , Parisi A. , Quaranta F. , Ciminelli E. , Di Gianfrancesco A. , Di Luigi L. , Pigozzi F.
Published: January 2017

The aim of the present study is to evaluate the effects induced by increasing concentrations of human recombinant growth hormone on T lymphocytes. Ten healthy volunteers and twelve subjects with symptomatic allergies were enrolled in the study. Peripheral blood mononuclear cells and purified T lymphocytes were cultured in the presence of graded concentrations of growth hormone. Following appropriate in vitro stimulations, the proportion of apoptotic T cells, the percentage of activated T lymphocyte subpopulations, the phytohemagglutinin responsiveness and the Th2 response were assessed by flow cytometry analysis. Moreover, in order to evaluate the phosphoinositol-3-kinase signaling pathway involvement, cells were also analyzed after treatment with LY294002. The treatment with different concentrations of growth hormone did not influence the activation pattern of un-stimulated T lymphocytes. On the contrary, growth hormone was able to modify the CD38/HLA-DR co-expression of T cells activated with phytohemoagglutinin. A different response was observed when samples obtained from healthy donors and from subjects with symptomatic allergies were analysed. Moreover, growth hormone treatment was able to increase the Th2 response in the samples obtained from healthy donors only. The results of the present study strongly support the hypothesis that growth hormone administration may play an important role in conditions of impaired/activated immune systems. The observation that growth hormone administration at high doses may reverse its effects and that it may promote a Th2-oriented response have significant clinical implications when considering the use of this hormone for artificially enhancing the physical performances of healthy athletes.
Neurotrophins, Their Receptors and KI-67 in Human GH-Secreting Pituitary Adenomas: An Immunohistochemical Analysis
Authors: Artico M. , Bianchi E. , Magliulo G. , De Vincentiis M. , De Santis E. , Orlandi A. , Santoro A. , Pastore F.S. , Giangaspero F. , Caruso R. , Re M. , Fumagalli L.
Published: January 2017

Pituitary adenomas are a diverse group of tumors arising from the pituitary gland. Typically, they are small, slow-growing, hormonally inactive lesions that come to light as incidental findings on radiologic or postmortem examinations, although some small, slow-growing lesions with excessive hormonal activity may manifest with a clinical syndrome. The family of neurotrophins plays a key role in the development and maintenance of the pituitary endocrine cell function and in the regulation of hypothalamo-pituitary-adrenocortical axis activity. The objective of our experimental study is to investigate the localization of the neurotrophins, their relative receptors and to detect the expression level of Ki-67 to determine whether all these factors participate in the transformation and development of human pituitary adenomas. A very strong expression of Neurotrophin-3 (NT-3) and its receptor TrKC was observed in the extracellular matrix (ECM) and vessel endothelium, together with a clear/marked presence of Brain-derived neurotrophic factor (BDNF), and its receptor TrKB, thus confirming their direct involvement in the progression of pituitary adenomas. On the contrary, NGF (Nerve growth factor) and its receptor TrKA and p75NTR were weakly expressed in the epithelial gland cells and the ECM.
Exhaled Nitric Oxide is Related to Bronchial Eosinophilia and Airway Hyperresponsiveness to Bradykinin in Allergen-Induced Asthma Exacerbation
Authors: Ricciardolo F.L.M. , Di Stefano A. , Silvestri M. , Van Schadewijk A.M. , Malerba M. , Hiemstra P.S. , Sterk P.J.
Published: January 2017

Exhaled nitric oxide (FeNO) has been associated with bronchial eosinophilia and with airway hyperresponsiveness (AHR) in mild stable asthma. We previously demonstrated in a large project that allergen exposure is able to raise FeNO and to worsen AHR to bradykinin. We postulated that allergen-induced increase in FeNO could be related to heightened mucosal eosinophils and AHR to bradykinin in atopic asthma. We performed a new immunohistochemical analysis on bronchial biopsy specimens, previously obtained from the same large project, in order to assess the number of mucosal eosinophils (EG-2+ cell) and other inflammatory cells at 48 hours after diluent and allergen exposures. Inflammatory cell counts were related to FeNO and AHR to BK (expressed as logPD20 bradykinin). In 10 atopic mild asthmatics, we found that the numbers of EG-2+ and CD4+ cells in bronchial submucosa were significantly increased after allergen compared to the respective counts after diluent (p < 0.01). EG-2+ cells in the bronchial submucosa were negatively correlated with logPD20 bradykinin only after allergen challenge (rho = −0.709, p = 0.027). We also found a positive strong correlation between EG-2+ cells and FeNO values in atopic asthmatics at 48 hours after both diluent (rho = 0.746, p = 0.017) and allergen (rho = 0.644, p = 0.049) challenge. FeNO values negatively correlated with responsiveness to bradykinin only after allergen challenge (rho = −0.675, p = 0.039). This study indicates that after allergen exposure heightened level of exhaled NO may reflect augmented airway eosinophilic inflammation and airway responsiveness to bradykinin indicating loss of asthma control.
Medical Management and Sublingual Immunotherapy Practices in Patients with House Dust Mite-Induced Respiratory Allergy: A Retrospective, Observational Study
Authors: Trebuchon F. , David M. , Demoly P.
Published: January 2017

The primary objective of this study is to retrospectively describe the treatment regimens (initiation, maintenance, dosage and duration) in sublingual immunotherapy (SLIT) with house dust mite (HDM) extracts in routine practice in France. The secondary objectives include a description of the respiratory allergies that led to treatment and an evaluation of the treatment's efficacy and safety, patient satisfaction and compliance (as assessed by the physician) and patient management practices. Randomly-selected allergy specialists each included ten patients over the age of five with a respiratory allergy and proven sensitization to HDM (positive skin test and/or specific IgE >0.7 kUI) and in whom SLIT had been initiated in 2002 or 2005. The participants were monitored for at least two years. A total of 139 physicians participated in the study and contributed data from 1,289 patients (57% of whom were under the age of 18). More than 70% of the patients suffered from moderate-to-severe allergic rhinitis and 50% also suffered from asthma. More than 60% of the patients were polysensitized. A shift to shorter SLIT protocols was observed over time. Longer protocols tended to be used in children. Compliance was deemed good or very good in 84% of the patients. Treatment was deemed effective or very effective in 82% of the patients. Symptoms of rhinitis and/or asthma improved in 66% and 63% of the patients respectively, with a concomitant reduction in symptomatic medication intake. The majority of the patients were satisfied with their treatment, which was well tolerated. The results of this large, retrospective, observational study confirm the efficacy and tolerability of HDM SLIT in routine French practice in a “real-world” setting.
Recurrent Acute Rhinosinusitis: A Single Blind Clinical Study of N-Acetylcysteine vs Ambroxol Associated to Corticosteroid Therapy
Authors: Macchi A. , Terranova P. , Castelnuovo P.
Published: January 2017

The aim of rhinosinusitis treatment is to restore sinusal eutrophism and to normalize ventilation and mucociliary transport. Frequently the improvement of sinusal physiological conditions is associated with a reduction of infections and pulmonary symptoms. The treatment of these diseases often requires the combination of medical and surgical strategies. In particular, the aim of the medical therapy is multiple: to treat the infection (with antibiotics), to reduce the mucosal swelling (with corticosteroids) and to improve mucus drainage (with mucolytics or muco-regulators). The use of atomized nasal douche, as a washing of the nasal fossas, is chosen because of its local action minimizing systemic adverse effects. The surgical treatment is secondary to medical failure, and it is focused on clearing the sinusal ostia in the sphenoethmoidal recess and the osteomeatal complex. In case of recurrent sinonasal diseases the importance of the surgical operation is represented by the fact that the medical treatment better reaches the target in the sinusal space. This study is focused on the primary medical treatment of acute recurrent rhinosinusitis. The patients who immediately needed surgical treatment were excluded from the study (because of the presence of an anatomical obstruction of the osteomeatal complex and/or the sphenoethmoidal recess, hence non-susceptible to improvement by medical therapy alone), and these patients were immediately addressed to undergo a CT scan examination in order to be involved in a future surgical programme. The medical treatment for those forms which do not require antibiotics (i.e. when infections are not involved), is based on the use of topical corticosteroids. While there are controversies on the real efficacy of adding mucolytic agents to the steroids, they are commonly prescribed in clinical practice, with the rationale of reducing viscosity and improving clearance of mucus in order to help the restoration of the physiological sinus conditions. The primary aim of the medical treatment is to reduce the number of acute episodes and thus to increase the time between the exacerbations, allowing a good quality of life without necessitating surgical procedure.
Neuroprotective and Anti-Inflammatory Activities of Atorvastatin in a Rat Chronic Constriction Injury Model
Authors: Chu L.W. , Chen J.Y. , Yu K.L. , Cheng K.I. , Chen I.J. , Wu P.C. , Wu B.N.
Published: January 2017

Atorvastatin is an HMG-CoA reductase inhibitor used to treat hypercholesterolemic conditions associated with hypertension. This study aims to investigate the anti-inflammatory and neuroprotective effects of atorvastatin on peripheral neuropathic pain. Peripheral neuropathic pain was induced by chronic constriction injury (CCI) in Sprague-Dawley rats. Rats were divided into 3 groups including sham-operated, CCI, and atorvastatin-treated. Atorvastatin (10 mg/kg) or phosphate-buffered saline was orally administered for 2 weeks. All animals were assessed by neurobehavioral tests before surgery and at days 3, 7, 14 after surgery. Inflammatory and neuroprotective factors were evaluated by Western blot analysis. eNOS, COX2 and iNOS in the sciatic nerve were also studied using immunohistochemistry. Atorvastatin attenuated CCI-induced nociceptive sensitization and thermal hyperalgesia in a time-dependent manner. Atorvastatin improved CCI-induced neurobehavioral/inflammatory activity by inhibition of TGF-β, PIκB/IκB, NFκB, COX2, iNOS, EP1 and EP4 in the sciatic nerve. Atorvastatin was also found to increase neuroprotection factors pAkt/Akt, eNOS and VEGF. Taken together, these data indicate that atorvastatin could protect the sciatic nerve against CCI-induced neuroinflammation and nociception.
A Comparative Study of Loratadine Syrup and Cyproheptadine HCL Solution for Treating Perennial Allergic Rhinitis in Taiwanese Children Aged 2–12 Years
Authors: Wu K.G. , Li T.H. , Wang T.Y. , Hsu C.L. , Chen C. J.
Published: January 2017

We assessed the efficacy of loratadine syrup compared with cyproheptadine HCl solution for treating children aged from 2 to 12 years with perennial allergic rhinitis (PAR) in Taiwan. Sixty children with mite-induced PAR were enrolled and randomly placed into two treatment groups: loratadine syrup or cyproheptadine HCl solution. Treatment efficacy and symptom changes from baseline to post-treatment were evaluated by total symptom scores and visual analogue scales (VAS) during a 2-week period. There were no differences in age, gender, height, or weight between the two groups. After 2 weeks of treatment, there was a significantly greater reduction in symptom scores in the loratadine group than in the cyproheptadine group ( p<0.001). Clinical and subjective VAS showed significant differences in percentage changes from baseline between the loratadine and cyproheptadine groups at all time points (all p<0.001, in favor of loratadine). Clinical VAS change at week 1: 95.1 vs 11.3; subjective VAS change at week 1: 88.6 vs 13.6; clinical VAS change at week 2: 125.5 vs 18.3; subjective VAS change at week 2: 101.4 vs 7.1. Thus, loratadine was superior to cyproheptadine for alleviating both nasal and non-nasal symptoms of perennial allergic rhinitis in Taiwanese children aged 2–12 years.
An IgE Immediate Reaction to Thiocolchicoside
Authors: Caimmi D. , Caviglioli S. , Raschetti R. , Demoly P.
Published: January 2017

Hypersensitivity reactions due to muscle relaxant drugs may be related either to a nonspecific release of allergic mediators or to allergic reactions induced by the molecules themselves. Rare cases of hypersensitivity reactions have been associated to thiocolchicoside, and no case of IgE-mediated immediate reaction has actually been reported to date. We report the first documented case of immediate anaphylaxis to thiocolchicoside.