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1.
J Endocrinol Invest ; 45(10): 2007-2017, 2022 Oct.
Article in English | MEDLINE | ID: mdl-35751803

ABSTRACT

PURPOSE: There is emerging evidence that radiomics analyses can improve detection of skeletal fragility. In this cross-sectional study, we evaluated radiomics features (RFs) on computed tomography (CT) images of the lumbar spine in subjects with or without fragility vertebral fractures (VFs). METHODS: Two-hundred-forty consecutive individuals (mean age 60.4 ± 15.4, 130 males) were evaluated by radiomics analyses on opportunistic lumbar spine CT. VFs were diagnosed in 58 subjects by morphometric approach on CT or XR-ray spine (D4-L4) images. DXA measurement of bone mineral density (BMD) was performed on 17 subjects with VFs. RESULTS: Twenty RFs were used to develop the machine learning model reaching 0.839 and 0.789 of AUROC in the train and test datasets, respectively. After correction for age, VFs were significantly associated with RFs obtained from non-fractured vertebrae indicating altered trabecular microarchitecture, such as low-gray level zone emphasis (LGLZE) [odds ratio (OR) 1.675, 95% confidence interval (CI) 1.215-2.310], gray level non-uniformity (GLN) (OR 1.403, 95% CI 1.023-1.924) and neighboring gray-tone difference matrix (NGTDM) contrast (OR 0.692, 95% CI 0.493-0.971). Noteworthy, no significant differences in LGLZE (p = 0.94), GLN (p = 0.40) and NGDTM contrast (p = 0.54) were found between fractured subjects with BMD T score < - 2.5 SD and those in whom VFs developed in absence of densitometric diagnosis of osteoporosis. CONCLUSIONS: Artificial intelligence-based analyses on spine CT images identified RFs associated with fragility VFs. Future studies are needed to test the predictive value of RFs on opportunistic CT scans in identifying subjects with primary and secondary osteoporosis at high risk of fracture.


Subject(s)
Osteoporosis , Osteoporotic Fractures , Spinal Fractures , Absorptiometry, Photon/methods , Artificial Intelligence , Bone Density , Cross-Sectional Studies , Humans , Lumbar Vertebrae/diagnostic imaging , Male , Osteoporosis/complications , Osteoporotic Fractures/diagnostic imaging , Spinal Fractures/complications , Spinal Fractures/diagnostic imaging , Tomography, X-Ray Computed/methods
2.
Transfus Clin Biol ; 29(3): 243-249, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35476961

ABSTRACT

OBJECTIVES: The International Haemovigilance Network's (IHN) ISTARE database collects surveillance data on all adverse reactions (AR) associated with transfusion of blood and blood components, facilitating the sharing of best practice and benchmarking for improving blood safety and quality. Up to 2012, no publications discussed certain rare AR. The aim of this study is to examine ISTARE data on AR from 2012 to 2016, focusing on hypotensive reactions, post-transfusion purpura (PTP), transfusion-associated graft versus host disease (TA-GvHD), hyperkalemia and hypocalcemia. MATERIALS AND METHODS: National Haemovigilance Systems (HVS), provided aggregate annual data on AR by type of reaction, severity, imputability to transfusion, and blood component implicated. Twenty-nine HVS provided 104 annual reports covering 107,778,290 blood units issued. RESULTS: Among AR reported, 25% were serious, including 368 deaths. The 284 transfusion-transmitted infections included 187 bacterial infections, 84 viral and 13 parasitic or fungal; nine deaths resulted. AR related to the respiratory system transfusion-associated circulatory overload, transfusion-related acute lung injury and transfusion-associated dyspnoea accounted for 8.3% of all AR, 20.1% of serious, and 52.2% of deaths. Of 1634 rare AR, 1565 were hypotensive, 38 PTP, 17 GvHD, 9 hyperkalemia and 5 hypercalcemia. Half were serious and 16 fatalities were recorded (13 hypotensive, 2 GvHD, one PTP). Among 14 countries that reported any hypotensive AR, incidences diverged widely. CONCLUSIONS: ARs in this group are frequently severe or life-threatening. Hypotensive AR are the most common, but may have been overlooked and counted under allergic and other AR presenting with hypotension. Compliance with the ISBT definition may be suboptimal, thus its real incidence may be higher. Data on GvHD may contribute to clarifying the role of leukodepletion with or without irradiation. ISTARE continues to be a useful surveillance tool for all transfusion AR and provides relevant insights into overlooked and rare AR, thus offering important contributions towards maximising transfusion safety.


Subject(s)
Graft vs Host Disease , Hyperkalemia , Transfusion Reaction , Blood Safety , Blood Transfusion , Graft vs Host Disease/epidemiology , Graft vs Host Disease/etiology , Humans , Hyperkalemia/epidemiology , Hyperkalemia/etiology , Transfusion Reaction/epidemiology , Transfusion Reaction/etiology
3.
Transfus Clin Biol ; 28(1): 55-59, 2021 Feb.
Article in English | MEDLINE | ID: mdl-33096208

ABSTRACT

BACKGROUND: Although the SARS-CoV-2 virus is transmitted mainly through the respiratory tract, possible transmission by transfusion from asymptomatic carriers should be explored. As yet there are no reports of transfusion transmission of COVID-19. Haemovigilance findings within a three-month surveillance period during the new coronavirus pandemic are presented. MATERIALS AND METHODS: Due to great demand and shortage, blood sessions in outpatient facilities were organized during the high prevalence period of COVID-19, alongside a national plan to monitor the evolving public health situation by random molecular screening of high-risk groups of the population. Haemovigilance protocols were implemented as well as surveillance for any COVID-19 case reported post-transfusion. A 14-day quarantine and follow-up molecular and antibody testing of any COVID-19 positive case was obligatory. RESULTS: Post-donation, post-transfusion information and molecular testing of swab samples collected from three asymptomatic donors at risk for COVID-19, revealed the case of an immunosupressed patient who had been transfused with whole blood derived platelets from a donor subsequently diagnosed with COVID-19. The recipient exhibited no symptoms of the disease. Molecular and antibody testing results were negative. CONCLUSION: Haemovigilance provided information supporting the absence of transfusion transmission of COVID-19, thus strengthening the hypothesis that, even if it cannot yet be definitively ruled out, COVID-19 is not transmitted through blood transfusion. As of early June 2020, a perfect test does not exist, therefore haemovigilance along with the implementation of strict proactive measures is crucial to identify eluding asymptomatic individuals and ensure blood safety during the pandemic.


Subject(s)
Blood Component Transfusion/adverse effects , Blood Donors , Blood Safety , COVID-19/transmission , Donor Selection/standards , Pandemics , SARS-CoV-2/isolation & purification , Viremia/transmission , Adult , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Asymptomatic Infections , COVID-19/blood , COVID-19/diagnosis , COVID-19/prevention & control , COVID-19 Testing , Contact Tracing , Female , Greece/epidemiology , Humans , Immunocompromised Host , Leukemia, Myeloid, Acute/drug therapy , Leukemia, Myeloid, Acute/therapy , Male , Middle Aged , Platelet-Rich Plasma , Police , Viremia/blood , Viremia/diagnosis
4.
Eur J Neurol ; 26(10): 1341-1344, 2019 10.
Article in English | MEDLINE | ID: mdl-30932272

ABSTRACT

BACKGROUND AND PURPOSE: Adrenomyeloneuropathy (AMN) is the most frequent metabolic hereditary spastic paraplegia. Accordingly, its main site of pathological changes is the spinal cord. It is difficult to quantify AMN progression because commonly used clinical scales have limitations and reliable biomarkers are lacking. The goal was to investigate whether spinal cord and brain quantitative magnetic resonance imaging may assess structural changes in AMN over a relatively short time period. METHODS: In this longitudinal observational study, the total cord areas (TCAs) from the C2-C3 to T2-T3 level and diffusion tensor imaging (DTI) metrics of the cervical spinal cord and brain portion of the corticospinal tracts in six AMN and six age-matched control subjects at baseline and at a mean follow-up of 22.6 months were assessed. RESULTS: A significant reduction of the mean TCA at the T1-T2 level (-3.79%) and a trend of reduction at the lowest cervical levels were observed only in AMN patients. Additionally, DTI metrics revealed significant changes in fractional anisotropy (-8.84%), mean diffusivity (+12.62%) and radial diffusivity (+25.91%) at the C2-C3 level. DISCUSSION: The study encourages the assessment of TCAs and spinal cord DTI metrics as surrogate outcome measures in AMN, by focusing on the cervical-thoracic junction and the uppermost part of the cervical spinal cord. Despite the limitation of the results due to the small number of investigated subjects, these observations are useful for forthcoming clinical trials in AMN and possibly other hereditary diseases with predominant spinal cord involvement.


Subject(s)
Adrenoleukodystrophy/diagnostic imaging , Magnetic Resonance Imaging/methods , Adult , Anisotropy , Diffusion Magnetic Resonance Imaging , Diffusion Tensor Imaging , Disease Progression , Female , Follow-Up Studies , Humans , Longitudinal Studies , Male , Middle Aged , Pyramidal Tracts/diagnostic imaging , Spinal Cord/diagnostic imaging
5.
QJM ; 111(5): 287-294, 2018 May 01.
Article in English | MEDLINE | ID: mdl-29385542

ABSTRACT

BACKGROUND: Despite the evidence that the patient gender is an important component in the intensive care unit (ICU) admission decision, the role of physician gender and the interaction between the two remain unclear. OBJECTIVE: To investigate the association of both the patient and the physician gender with ICU admission rate of critically ill emergency department (ED) medical patients in a hospital with restricted ICU bed capacity operates with 'closed door' policy. METHODS: A retrospective population-based cohort analysis. We included patients above 18 admitted to an ED resuscitation room (RR) of a tertiary hospital during 2011-12. Data on medical, laboratory and clinical characteristics were obtained. We used an adjusted multivariable logistic regression to analyze the association between both the patient and the physician gender to the ICU admission decision. RESULTS: We included 831 RR admissions, 388 (46.7%) were female patients and 188 (22.6%) were treated by a female physicians. In adjusted multivariable analysis (adjusted for age, diabetes, mode of hospital transportation, first pH and patients who were treated with definitive airway and vasso-pressors in the RR), female-female combination (patient-physician, respectively) showed the lowest likelihood to be admitted to ICU (adjusted OR: 0.21; 95% CI: 0.09-0.51) compared to male-male combination, in addition to a smaller decrease among female-male (adjusted OR: 0.53; 95% CI: 0.32-0.86) and male-female (adjusted OR: 0.43; 95% CI: 0.21-0.89) combinations. CONCLUSION: We demonstrated the existence of the possible gender bias where female gender of the patient and treating physician diminish the likelihood of the restricted health resource use.


Subject(s)
Hospitalization/statistics & numerical data , Intensive Care Units/statistics & numerical data , Patient Admission/statistics & numerical data , Physician-Patient Relations , Sexism , Adult , Aged , Aged, 80 and over , Clinical Competence , Clinical Decision-Making , Female , Hospital Bed Capacity , Humans , Israel , Kaplan-Meier Estimate , Male , Middle Aged , Patient Admission/standards , Retrospective Studies , Sex Factors
6.
Eur J Clin Microbiol Infect Dis ; 37(1): 43-50, 2018 Jan.
Article in English | MEDLINE | ID: mdl-28879405

ABSTRACT

We evaluated an infection control (IC) program influenced by personnel and material resource shortages on the incidence of bloodstream infections (BSI) due to carbapenem-resistant Klebsiella pneumoniae (CRKP), Acinetobacter baumannii (CRAB), and Pseudomonas aeruginosa (CRPA) in an endemic region. Between January 2010 and December 2015, all BSI episodes caused by CRKP, CRAB, and CRPA were recorded. An IC bundle was implemented in January 2012. We evaluated the effect of the interventions on BSI rates between the pre-intervention (2010-2011) and intervention (2012-2013) periods, using an interrupted time-series model. From 2014, when interventions were still applied, BSI incidence was gradually increased. For this reason, we evaluated with a linear mixed effects model several factors possibly contributing to this increase for the years 2012-2015, which was considered as the intervention/follow-up period. During the study period, 351 patients with BSI were recorded, with a total of 538 episodes; the majority (83.6%) occurred in the intensive care unit (ICU). The BSI incidence rate per year during 2010-2015 for ICU patients was 21.03/19.63/17.32/14.45/22.85/25.02 per 1000 patient-days, respectively, with the reduction in BSI levels after the start of intervention marginal (p = 0.054). During the follow-up period (2014-2015), the most influential factors for the increased BSI incidence were the reduced participation in educational courses and compliance with hand hygiene. The implementation of IC interventions reduced the BSI incidence rates, particularly for ICU patients. However, factors possibly related to the restrictions of human and material resources apparently contributed to the observed expansion of BSI in our endemic setting.


Subject(s)
Acinetobacter Infections/epidemiology , Bacteremia/epidemiology , Cross Infection/epidemiology , Infection Control/methods , Klebsiella Infections/epidemiology , Pseudomonas Infections/epidemiology , Acinetobacter Infections/drug therapy , Acinetobacter Infections/microbiology , Acinetobacter baumannii/drug effects , Anti-Bacterial Agents/therapeutic use , Bacteremia/drug therapy , Bacteremia/microbiology , Bacterial Proteins/genetics , Carbapenems/therapeutic use , Cross Infection/drug therapy , Cross Infection/microbiology , Drug Resistance, Bacterial/genetics , Female , Germany/epidemiology , Humans , Intensive Care Units , Klebsiella Infections/drug therapy , Klebsiella Infections/microbiology , Klebsiella pneumoniae/drug effects , Male , Microbial Sensitivity Tests , Middle Aged , Pseudomonas Infections/drug therapy , Pseudomonas Infections/microbiology , Pseudomonas aeruginosa/drug effects , Tertiary Care Centers , beta-Lactamases/genetics
7.
Osteoarthritis Cartilage ; 25(4): 589-599, 2017 04.
Article in English | MEDLINE | ID: mdl-27836674

ABSTRACT

OBJECTIVE: Osteoarthritis (OA), the most common chronic degenerative joint disease, is characterized by joint structure changes and inflammation, both mediated by the IκB kinase (IKK) signalosome complex. The ability of N-acetyl phenylalanine derivative (NAPA) to increase cartilage matrix components and to reduce inflammatory cytokines, inhibiting IKKα kinase activity, has been observed in vitro. The present study aims to further clarify the effect of NAPA in counteracting OA progression, in an in vivo mouse model after destabilization of the medial meniscus (DMM). DESIGN: 26 mice were divided into three groups: (1) DMM surgery without treatment; (2) DMM surgery treated after 2 weeks with one intra-articular injection of NAPA (2.5 mM) and (3) no DMM surgery. At the end of experimental times, both knee joints of the animals were analyzed through histology, histomorphometry, immunohistochemistry and microhardness of subchondral bone (SB) tests. RESULTS: The injection of NAPA significantly improved cartilage thickness (CT) and reduced Chambers and Mankin modified scores and fibrillation index (FI), with weaker MMP13, ADAMTS5, MMP10 and IKKα staining. The microhardness measurements did not shown statistically significant differences between the different groups. CONCLUSIONS: NAPA markedly improved the physical structure of articular cartilage while reducing catabolic enzymes, extracellular matrix (ECM) remodeling and IKKα expression, showing to be able to exert a chondroprotective activity in vivo.


Subject(s)
Cartilage, Articular/drug effects , Glucosamine/pharmacology , Knee Joint/drug effects , Osteoarthritis, Knee/immunology , Phenylalanine/analogs & derivatives , ADAMTS5 Protein/drug effects , ADAMTS5 Protein/metabolism , Animals , Cartilage, Articular/metabolism , Cartilage, Articular/pathology , Disease Models, Animal , I-kappa B Kinase/drug effects , I-kappa B Kinase/metabolism , Inflammation , Injections, Intra-Articular , Knee Joint/immunology , Knee Joint/metabolism , Knee Joint/pathology , Male , Matrix Metalloproteinase 10/drug effects , Matrix Metalloproteinase 10/metabolism , Matrix Metalloproteinase 13/drug effects , Matrix Metalloproteinase 13/metabolism , Menisci, Tibial/surgery , Mice , Organ Size , Osteoarthritis, Knee/metabolism , Osteoarthritis, Knee/pathology , Phenylalanine/pharmacology
9.
Eur Arch Otorhinolaryngol ; 273(6): 1449-53, 2016 Jun.
Article in English | MEDLINE | ID: mdl-26321749

ABSTRACT

The role of inferior turbinate hypertrophy in the reduction of nasal airflow is well established. Although chronic nasal obstruction is not life- threatening, it significantly impairs patients' quality of life, affecting many aspects of daily activities; therefore, patients seek medical intervention. 40 patients were selected (27 males and 13 females) between 27 and 64 years of age with a symptom of nasal obstruction. The patients were divided in two groups: Group 1: coblation, 25 patients (18 males and 7 females); Group 2: radiofrequency, 15 patients (7 males and 6 females). These 40 patients were followed for 3 years. Patients were analyzed using both subjective and objective methods. The visual analog scale (VAS) subjective data and objective data including both active anterior rhinomanometry and acoustic rhinometry were recorded and analyzed. Data were collected pre-operatively and at 1 and 3 years post-operatively. According to our data, both coblation and radiofrequency turbinate reduction benefit patients with good results. The complications, found during the follow-up, are limited to minimal bleeding and crusting. Coblation and radiofrequency were significantly less painful than others procedures during the early post-operative period. In our study, both coblation and radiofrequency provide an improvement in nasal airflow with a reduction in nasal obstructive symptoms in the short term, but their efficacy tended to decrease within 3 years.


Subject(s)
Catheter Ablation/methods , Nasal Obstruction/surgery , Turbinates/pathology , Turbinates/surgery , Adult , Female , Humans , Hypertrophy/surgery , Male , Middle Aged , Nasal Obstruction/etiology , Rhinomanometry , Rhinometry, Acoustic , Visual Analog Scale
10.
J Endocrinol Invest ; 38(12): 1345-56, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26335301

ABSTRACT

PURPOSE: The pollutant Cadmium (Cd) is widespread in the environment and causes alterations of human health by acting as an endocrine disruptor. Bone tissue seems to be a crucial target of Cd contamination. Indeed, we have previously demonstrated that this endocrine disruptor induces osteoblast apoptosis and necrosis. Thus, aim of this study was to further evaluate the effect of Cd on osteoblasts homeostasis, investigating potential modification of the Wnt/ß-catenin intracellular pathway, the intracellular process involved in programmed cellular death and the cytoskeletal alterations. MATERIAL AND METHODS: To this purpose, human osteoblastic Saos-2 cells, a human osteosarcoma osteoblast-like cell line, were cultured and treated with Cd. RESULTS: Osteoblastic cells were treated for 6 h with 10µM Cd, which induced nuclear translocation of ß-catenin and increased expression of Wnt/ß-catenin target genes. Longer exposure to the same Cd concentration induced osteoblastic cell apoptosis. To better characterize the intracellular events involved in these Cd-induced alterations, we evaluated the effect of Cd exposure on actin filaments and proteins associated to cytoskeletal actin, characterized by the presence of LIM domains. Long (15, 24 h) exposure of osteoblasts to Cd reduced LIM proteins expression and induced actin filaments destruction and a significant caspase-3 activation after 24 h. In addition, to prove that Cd induces osteoblastic cells apoptosis after long exposure, we performed TUNEL assay which demonstrated increase of cell apoptosis after 24 h. CONCLUSION: In conclusion, our study shows that osteoblasts exposed to Cd for short intervals of time demonstrated an increase in cell proliferation through a Wnt/ß-catenin dependent mechanism, likely as a compensatory mechanism in response to cell injury. Longer exposure to the same Cd concentration induced cells apoptosis through cytoskeleton disruption-mediated mechanisms and caspase activation.


Subject(s)
Actin Cytoskeleton/drug effects , Cadmium/pharmacology , Endocrine Disruptors/pharmacology , Homeostasis/drug effects , Osteoblasts/drug effects , Wnt Signaling Pathway/drug effects , Apoptosis/drug effects , Cell Differentiation/drug effects , Cell Line, Tumor , Humans , In Vitro Techniques
11.
Eur J Nucl Med Mol Imaging ; 42(7): 1093-105, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25813354

ABSTRACT

PURPOSE: Hypoxia-inducible factor 1α (HIF-1α) activity is one of the major players in hypoxia-mediated glioma progression and resistance to therapies, and therefore the focus of this study was the evaluation of HIF-1α modulation in relation to tumour response with the purpose of identifying imaging biomarkers able to document tumour response to treatment in a murine glioma model. METHODS: U251-HRE-mCherry cells expressing Luciferase under the control of a hypoxia responsive element (HRE) and mCherry under the control of a constitutive promoter were used to assess HIF-1α activity and cell survival after treatment, both in vitro and in vivo, by optical, MRI and positron emission tomography imaging. RESULTS: This cell model can be used to monitor HIF-1α activity after treatment with different drugs modulating transduction pathways involved in its regulation. After temozolomide (TMZ) treatment, HIF-1α activity is early reduced, preceding cell cytotoxicity. Optical imaging allowed monitoring of this process in vivo, and carbonic anhydrase IX (CAIX) expression was identified as a translatable non-invasive biomarker with potential clinical significance. A preliminary in vitro evaluation showed that reduction of HIF-1α activity after TMZ treatment was comparable to the effect of an Hsp90 inhibitor, opening the way for further elucidation of its mechanism of action. CONCLUSION: The results of this study suggest that the U251-HRE-mCherry cell model can be used for the monitoring of HIF-1α activity through luciferase and CAIX expression. These cells can become a useful tool for the assessment and improvement of new targeted tracers for potential theranostic procedures.


Subject(s)
Antineoplastic Agents/therapeutic use , Biomarkers, Tumor/metabolism , Brain Neoplasms/drug therapy , Dacarbazine/analogs & derivatives , Glioma/drug therapy , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Animals , Biomarkers, Tumor/genetics , Carbonic Anhydrases/genetics , Carbonic Anhydrases/metabolism , Cell Line, Tumor , Dacarbazine/therapeutic use , Drug Evaluation, Preclinical/methods , Female , Humans , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , Luminescent Proteins/genetics , Luminescent Proteins/metabolism , Mice , Mice, Nude , Optical Imaging , Temozolomide
12.
Cell Death Dis ; 6: e1663, 2015 Feb 26.
Article in English | MEDLINE | ID: mdl-25719247

ABSTRACT

Mitochondrial fission and fusion are essential processes in the maintenance of the skeletal muscle function. The contribution of these processes to muscle development has not been properly investigated in vivo because of the early lethality of the models generated so far. To define the role of mitochondrial fission in muscle development and repair, we have generated a transgenic mouse line that overexpresses the fission-inducing protein Drp1 specifically in skeletal muscle. These mice displayed a drastic impairment in postnatal muscle growth, with reorganisation of the mitochondrial network and reduction of mtDNA quantity, without the deficiency of mitochondrial bioenergetics. Importantly we found that Drp1 overexpression activates the stress-induced PKR/eIF2α/Fgf21 pathway thus leading to an attenuated protein synthesis and downregulation of the growth hormone pathway. These results reveal for the first time how mitochondrial network dynamics influence muscle growth and shed light on aspects of muscle physiology relevant in human muscle pathologies.


Subject(s)
Dynamins/metabolism , Muscle, Skeletal/metabolism , Animals , Blotting, Western , DNA, Mitochondrial/metabolism , Dynamins/genetics , Immunoprecipitation , Membrane Potential, Mitochondrial/genetics , Membrane Potential, Mitochondrial/physiology , Mice , Mice, Transgenic , Oxygen Consumption/physiology
13.
Osteoarthritis Cartilage ; 23(1): 103-13, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25219669

ABSTRACT

OBJECTIVE: Aim of this study is to investigate the effects of Glucosamine (GlcN) and its peptidyl-derivative, 2-(N-Acetyl)-L-phenylalanylamido-2-deoxy-ß-D-glucose (NAPA), on extracellular matrix (ECM) synthesis in human primary chondrocytes (HPCs). METHODS: Dose-dependent effect of GlcN and NAPA on Glycosaminoglycan (GAG), Collagen type II (Col2) and Small Leucine-Rich Proteoglycans (SLRPs) was examined by incubating HPCs, cultured in micromasses (3D), with various amounts of two molecules, administered as either GlcN alone or NAPA alone or GlcN plus NAPA (G + N). Immunohystochemical and immunofluorescent staining and biochemical analysis were used to determine the impact of the two molecules on ECM production. Gene expression analysis was performed by TaqMan Real-Time Polymerase Chain Reaction (PCR) assays. RESULTS: The lowest concentration to which GlcN and NAPA were able to affect ECM synthesis was 1 mM. Both molecules administered alone and as G + N stimulated GAGs and SLRPs synthesis at different extent, NAPA and mainly G + N stimulated Col2 production, whereas GlcN was not effective. Both molecules were able to induce Insulin Growth Factor-I (IGF-I) and to stimulate SOX-9, whereas NAPA and G + N were able to up-regulate both Hyaluronic Acid Synthase-2 and Hyaluronic acid. Very interesting is the synergistic effect observed when chondrocyte micromasses were treated with G + N. CONCLUSIONS: The observed anabolic effects and optimal concentrations of GlcN and NAPA, in addition to beneficial effects on other cellular pathways, previously reported, such as the inhibition of IKKα, could be useful to formulate new cartilage repair strategies.


Subject(s)
Chondrocytes/drug effects , Chondrocytes/metabolism , Collagen Type II/biosynthesis , Extracellular Matrix/metabolism , Glucosamine/analogs & derivatives , Glucosamine/pharmacology , Glycosaminoglycans/biosynthesis , Proteoglycans/biosynthesis , Cells, Cultured , Dose-Response Relationship, Drug , Humans
14.
Mater Sci Eng C Mater Biol Appl ; 46: 409-16, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25492005

ABSTRACT

A nanostructured coating layer on titanium implants, able to improve their integration into bones and to protect against the harsh conditions of body fluids, was obtained by Ion Plating Plasma Assisted, a method suitable for industrial applications. A titanium carbide target was attached under vacuum to a magnetron sputtering source powered with a direct current in the 500-1100 W range, and a 100 W radio frequency was applied to the sample holder. The samples produced at 900 W gave the best biological response in terms of overexpression of some genes of proteins involved in bone turnover. We report the characterization of a reference and of an implant sample, both obtained at 900 W. Different micro/nanoscopic techniques evidenced the morphology of the substrates, and X-ray Photoelectron Spectroscopy was used to disclose the surface composition. The layer is a 500 nm thick hard nanostructure, composed of 60% graphitic carbon clustered with 15% TiC and 25% Ti oxides.


Subject(s)
Carbon , Graphite , Nanostructures , Osseointegration , Prostheses and Implants , Titanium , Biocompatible Materials , Cells, Cultured , Humans , Microscopy, Atomic Force , Microscopy, Electron, Scanning , Photoelectron Spectroscopy , Surface Properties
15.
AJNR Am J Neuroradiol ; 35(1): 170-5, 2014 Jan.
Article in English | MEDLINE | ID: mdl-23868150

ABSTRACT

BACKGROUND AND PURPOSE: DWI has been increasingly used to characterize orbital masses and provides quantitative information in the form of the ADC, but studies of DWI of orbital masses have shown a range of reported sensitivities, specificities, and optimal threshold ADC values for distinguishing benign from malignant lesions. Our goal was to determine the optimal use of DWI for imaging orbital masses through aggregation of data from multiple centers. MATERIALS AND METHODS: Source data from 3 previous studies of orbital mass DWI were aggregated, and additional published data points were gathered. Receiver operating characteristic analysis was performed to determine the sensitivity, specificity, and optimal ADC thresholds for distinguishing benign from malignant masses. RESULTS: There was no single ADC threshold that characterized orbital masses as benign or malignant with high sensitivity and specificity. An ADC of less than 0.93 × 10(-3) mm(2)/s was more than 90% specific for malignancy, and an ADC of less than 1.35 × 10(-3) mm(2)/s was more than 90% sensitive for malignancy. With these 2 thresholds, 33% of this cohort could be characterized as "likely malignant," 29% as "likely benign," and 38% as "indeterminate." CONCLUSIONS: No single ADC threshold is highly sensitive and specific for characterizing orbital masses as benign or malignant. If we used 2 thresholds to divide these lesions into 3 categories, however, a majority of orbital masses can be characterized with >90% confidence.


Subject(s)
Diffusion Magnetic Resonance Imaging/methods , Image Interpretation, Computer-Assisted/methods , Models, Statistical , Orbital Neoplasms/pathology , Statistics as Topic , Computer Simulation , Female , Humans , Male , Reproducibility of Results , Sensitivity and Specificity
16.
Surg Radiol Anat ; 35(9): 863-5, 2013 Nov.
Article in English | MEDLINE | ID: mdl-23468000

ABSTRACT

We report a case of a patient with right type I proatlantal intersegmental artery associated with right fetal posterior cerebral artery and absence of both vertebral arteries and of the left posterior communicating artery. We also describe the clinical relevance of these findings for this patient. A 56-year-old woman with vertigo and tinnitus underwent contrast enhanced Magnetic Resonance Angiography (MRA) of the supra-aortic arteries using a 1.5 Tesla scanner. Maximum intensity projection and volume rendering reconstructions were obtained. MRA demonstrated the persistence of an anastomotic artery between the right internal carotid artery and basilar artery, passing through the foramen magnum, suggesting a type I proatlantal intersegmental artery. The examination also showed the absence of both vertebral arteries and the presence of a right fetal-type posterior cerebral artery. To our knowledge, this is the first report of a type I proatlantal intersegmental artery associated with an omolateral fetal-type posterior cerebral artery and the absence of both vertebral arteries and of the left posterior communicating artery. This condition requires a watchful monitoring of the patient and has to be considered in case of surgical procedures of the carotid arteries.


Subject(s)
Cerebral Arteries/abnormalities , Vertebral Artery/abnormalities , Cerebral Arteries/diagnostic imaging , Female , Humans , Magnetic Resonance Angiography , Middle Aged , Ultrasonography , Vertebral Artery/diagnostic imaging
17.
J Endocrinol Invest ; 35(2): 198-208, 2012 Feb.
Article in English | MEDLINE | ID: mdl-21697648

ABSTRACT

Cadmium is a widespread environmental pollutant which induces severe toxic alterations, including osteomalacia and osteoporosis, likely by estrogen receptor-dependent mechanisms. Indeed, cadmium has been described to act as an endocrine disruptor and its toxicity is exerted both in vivo and in vitro through induction of apoptosis and/or necrosis by not fully clarified intracellular mechanism(s) of action. Aim of the present study was to further investigate the molecular mechanism by which cadmium might alter homeostasis of estrogen target cells, such as osteoblast homeostasis, inducing cell apoptosis and/or necrosis. Human osteoblastic cells (hFOB 1.19) in culture were used as an in vitro model to characterize the intracellular mechanisms induced by this heavy metal. Cells were incubated in the presence/ absence of 10-50 µM cadmium chloride at different times and DNA fragmentation and activation of procaspases- 8 and -3 were induced upon CdCl(2) treatment triggering apoptotic and necrotic pathways. Addition of caspase-8 and -3 inhibitors (Z-IETD-FMK and Z-DQMD-FMK) partially blocked these effects. No activation of procaspase-9 was observed. To determine the role of mitogen-activated protein kinases (MAPK) in these events, we investigated c-jun N-terminal kinase (JNK), p38 and extracellular signal-regulated protein kinase (ERK1/2) phosphorylation which were activated by 10 µM CdCl(2). Chemical inhibitors of JNK, p38, and ERK1/2, SP600125, SB202190, and PD98059, significantly reduced the phosphorylation of the kinases and blunted apoptosis. In contrast, caspase inhibitors did not reduce the cadmium-induced MAPK phosphorylation, suggesting an independent activation of these pathways. In conclusion, at least 2 pathways appear activated by cadmium in osteoblasts: a direct induction of caspase-8 followed by activation of caspase-3 and an indirect induction by phosphorylation of ERK1/2, p38, and JNK MAPK triggering activation of caspase-8 and -3.


Subject(s)
Apoptosis/drug effects , Cadmium/toxicity , Caspases/physiology , MAP Kinase Signaling System/drug effects , Osteoblasts/drug effects , Cadmium/pharmacology , Caspases/metabolism , Cell Survival/drug effects , Cells, Cultured , DNA Damage/drug effects , DNA Damage/physiology , Dose-Response Relationship, Drug , Enzyme Activation/drug effects , Humans , MAP Kinase Signaling System/physiology , Necrosis/chemically induced , Osteoblasts/enzymology , Osteoblasts/pathology , Osteoblasts/physiology , Phosphorylation/drug effects , Protein Kinase Inhibitors/pharmacology , Signal Transduction/drug effects , Signal Transduction/physiology
19.
Minerva Cardioangiol ; 59(6): 591-600, 2011 Dec.
Article in English | MEDLINE | ID: mdl-22134471

ABSTRACT

Stroke is the third most common cause of death in North America and ever year approximately 700,000 new strokes are reported in the United States. Seventy-five percent of these occur in the distribution of the carotid arteries. Among strokes of a thromboembolic etiology, carotid occlusive disease is the most common cause. As many as 150,300 stroke-related fatalities are documented annually, with a total cost for the health-care system of approximately $ 18 billion per year. This review will focus on the different pathomorphologic aspects of carotid plaque, outlining the similarities and differences with the coronary plaque, with particular attention on how intravascular imaging may contribute to a better stratification of the patient treatment.


Subject(s)
Angioplasty, Balloon , Carotid Stenosis/diagnostic imaging , Carotid Stenosis/therapy , Plaque, Atherosclerotic/diagnostic imaging , Stents , Stroke/prevention & control , Ultrasonography, Interventional , Carotid Artery Diseases/diagnostic imaging , Carotid Artery Diseases/therapy , Carotid Stenosis/complications , Carotid Stenosis/economics , Carotid Stenosis/epidemiology , Evidence-Based Medicine , Humans , Incidence , Italy/epidemiology , Risk Assessment , Stroke/etiology , Treatment Outcome
20.
Minerva Stomatol ; 60(7-8): 349-58, 2011.
Article in English, Italian | MEDLINE | ID: mdl-21709650

ABSTRACT

AIM: Numerous studies have shown how the disc displacement, which usually occurs in an antero-medial direction, can be a factor contributing to temporomandibular joint (TMJ) pain and dysfunction. The aim of this study was to ascertain, through a critical review of the literature, current knowledge relating to anterior articular disc (ADD) in the rabbit that constitutes an extremely suitable animal model for studying the human TMJ. METHODS: An electronic search of the MEDLINE database was performed without applying time or language restrictions and using the following key words: TMD, anterior disc displacement, rabbit, bilaminar zone. This was followed by a manual search. The articles identified were assessed to verify their pertinence, or otherwise, to the topic of investigation. RESULTS: The articles examined were divided into the following groups according to the topic (histological and/or functional) they dealt with: experimental animal models, joint changes, elastic fibers, collagen, chondrocytes and nervous tissue. CONCLUSION: The papers reviewed covered many aspects, both microscopic and histochemical, of the dysfunctional picture o anterior ADD, furnishing a vast body of useful information, not only from the point of view of the results recorded, but also as regards the various surgical and analytical methods used.


Subject(s)
Fibrocartilage/pathology , Hernia/pathology , Models, Animal , Rabbits/physiology , Temporomandibular Joint Disorders/pathology , Animals , Collagen/analysis , Elastic Tissue/pathology , Fibrocartilage/surgery , Hernia/physiopathology , Humans , Ligaments, Articular/pathology , Ligaments, Articular/surgery , Pain/physiopathology , Species Specificity , Temporomandibular Joint/innervation , Temporomandibular Joint Disorders/physiopathology , Temporomandibular Joint Disorders/surgery
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