ABSTRACT
This research aims at assessing the environmental impacts exerted by a smart motorway compared to those of a traditional motorway. The study has global policy implications: it takes into account the impacts due to the construction and maintenance of the infrastructure and the environmental effects produced by the traffic emissions, taking into account smart technologies and truck platooning regulation. Through a classical LCA approach, 1 km-long smart motorway with 2 m-high embankment was assumed as the functional unit for the analysis. A realistic traffic condition has been considered. A comparison between environmental effects produced by the use of virgin material and by Reclaimed Asphalt Pavement was made by assuming two maintenance plans. Thanks to C-ITS systems the greater safety featured by smart motorways has a significant effect on the environmental impact, compared to conventional motorways. The impact produced by safety barriers during the life cycle was also estimated. For smart motorways the impact categories GWP, POCP, AP and EP are observed to be considerably reduced in the maintenance phase of zinc-coated steel safety barriers and in those associated to traffic emissions. It must be noted that in smart motorways vehicle emissions are markedly influenced by the percentage of heavy vehicles travelling in Truck Platooning mode. The results show that concomitant use of lime stabilization and RAP leads to a significant reduction in energy consumption (up to 35%) and pollutant emissions (up to 34% of CO2) than in case of exclusive use of virgin material. The accidents reduction produce a 30% decrease of GWP, POCP, AP and EP related to safety barriers maintenance phase than the corresponding values of traditional motorway. Truck platooning mode generates GWP reduction close to 4%. The environmental advantages of a smart motorway increase progressively with the increase of AADT, platooning truck percentage and heavy vehicles percentage.
ABSTRACT
Municipal solid waste (MSW) management constitutes a highly challenging issue to cope with in order of moving towards more sustainable urban policies. Despite new Standards call for recycling and reusing materials contained in the urban waste, several municipalities still use landfilling as a waste disposal method. Other than the environmental pressure exerted by these plants, waste transportation from the collection points to the landfill needs a specific attention to correctly assess the whole burden of the waste management systems. In this paper, the Ecological Footprint (EF) indicator is applied to the actual MSW of the city of Palermo (Sicily). Results show that the effects produced by the involved transportation vehicles are not negligible, compared to those generated by the other segments of the waste management system. This issue is further deepened by analysing the role of transportation in an upgraded waste management system that is represented by the newly designed waste management plan of Palermo. The computed saved ecological footprint is used here for suitably comparing the environmental performances of the MSW system in both scenarios. Finally, the suitability of the EF method to address not only complete waste management plans but also single segments of the waste management system, is also discussed.
Subject(s)
Solid Waste , Transportation , Waste Management , Cities , Refuse Disposal , SicilyABSTRACT
Papillary glioneuronal tumor (PGNT) is a recently described central nervous system neoplasm that mostly occurs in the supratentorial system, adjacent to the lateral ventricles. In 2007, WHO classified PGNT as grade I neuronal-glial tumor because of the characteristic papillary architecture and bipartite (astrocytic and neuronal/neurocytic) cell population. As a newly established entity of mixed glioneuronal tumor family, PGNT attracted extensive attention recently. In our report we discuss the clinical, neuroradiological and surgical features. The final result is compared with literature data.
Subject(s)
Ganglioglioma/diagnosis , Ganglioglioma/surgery , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/surgery , Supratentorial Neoplasms/diagnosis , Supratentorial Neoplasms/surgery , Adult , Contrast Media , Diagnosis, Differential , Female , Humans , Magnetic Resonance Imaging , Neoplasm Staging , Neurosurgical Procedures/methods , Reoperation , Tomography, X-Ray Computed , Treatment OutcomeABSTRACT
During the past decade, total knee arthroplasty (TKA) has been markedly increased. Recently, patient-specific custom cutting guides have been commercially introduced in order to achieve an accurate component alignment during TKA. In fact, these cutting blocks are specific to a patient's knee anatomy and should help the surgeons to perform bone cuts, reducing the complexity of conventional alignment and sizing tools. Nevertheless, there are critical arguments against patient-specific cutting guides for routine use, such as poor evidence and higher costs. Additionally, there are still no mild and long-term results available that describe the clinical outcomes following patient-specific instrumentation of TKR, cost-effectiveness and lower revision rates. Aim of the current manuscript was to describe the recent improvements of the surgical technique and instrumentation of TKA, reviewing the recent literature concerning the PSI technology.
Subject(s)
Arthroplasty, Replacement, Knee/methods , Knee Joint/surgery , Arthroplasty, Replacement, Knee/instrumentation , Evidence-Based Medicine , Humans , Knee Prosthesis , Magnetic Resonance Imaging/methods , Practice Guidelines as Topic , Surgery, Computer-Assisted/methods , Tomography, X-Ray Computed/methods , Treatment OutcomeABSTRACT
BACKGROUND: Internal haemorrhagic pachymeningiosis (IHP) is a rare disease characterized by a fibrous thickening and inflammatory infiltration in dural space mimicking chronic subdural hematoma. The pathogenesis of IHP is not entirely clear yet and treatment is still controversial. OBJECTIVE: We want to emphasize the importance of differentiating pachymeningiosis from chronic subdural hematoma as distinct pathological entities. PATIENTS AND METHODS: The records of five selected cases of IHP histologically confirmed were reviewed, focusing onset, neuroimaging, surgery and outcomes. CONCLUSIONS: IHP is most likely underestimated. Only through multidisciplinary approach it is possible to plane the proper therapeutic strategy. The diagnosis of IHP is confirmed by definitive histology but in some cases is possible with intraoperative frozen section.
Subject(s)
Dura Mater , Hematoma, Subdural, Chronic/surgery , Intracranial Hemorrhages/diagnosis , Intracranial Hemorrhages/surgery , Adult , Aged , Aged, 80 and over , Diagnosis, Differential , Female , Hematoma, Subdural, Chronic/complications , Humans , Intracranial Hemorrhages/etiology , MaleABSTRACT
AIM: To report on our routine use of TachoSil® for dural repair in neurosurgical practice. METHOD: TachoSil® has been applied in different fields of surgery thus far. When using TachoSil®, fibrinogen and thrombin is provided locally at the site of the dural defects. Upon contact with fluid, the clotting factors of TachoSil® dissolve and form a fibrin network, which glues the collagen sponge to the wound surface. RESULTS: In our experience, TachoSil® was found to be effective as support for the suture of the dura in patients undergoing spinal and cranial neurosurgical operations. Two illustrative examples are shown. CONCLUSIONS: Our procedure showed that closing the dural defect with TachoSil® is a technically simple, reliable and safe method for patients. Indeed, no post-operative cerebrospinal fluid leakage was observed. Nonetheless, further studies with larger sample size are warranted to confirm the efficacy of TachoSil® patches for dural repair.
Subject(s)
Brain Ischemia/surgery , Dura Mater/surgery , Fibrinogen , Meningeal Neoplasms/surgery , Meningioma/surgery , Neurosurgical Procedures , Thrombin , Aged , Drug Combinations , Female , Humans , Male , Middle Aged , Wound HealingABSTRACT
Eosinophilic granuloma (EG), Letterer-Siwe disease and Hand-Schuller-Christian disease are collectively called Langherans-cell histiocytosis (LCH). While the latter two are systemic diseases, the former is a localized form of histiocytosis. Solitary EG of the skull are rare lesions characterized by a natural history not well defined yet. In this context, we report a case of a 23-year-old male suffering for a recurrent and progressive right parietal headache. On computed tomography (CT) it was observed an ostelytic lesion which on magnetic resonance imaging (MRI) appeared as an hyperintense soft mass on both T1 and T2 weighted images. The lesion showed a marked and heterogeneous enhancement after gadolinium administration. The surgical excision was complete and the severe headache disappeared. Immunohistochemical analysis of the specimen indicated an eosinophilic granuloma characterized by Ki-67 nuclear antigen expression with a labeling index of 20%. In the pertinent literature we have found two aggressive cases of EG showing the Ki-67 expression with a respectively 6.2% (occipital bone granuloma) and 10% (parietal bone granuloma) labeling index. That high proliferative activity suggests a local Langherans' cell proliferation along with an exuberant inflammatory response and also explains the aggressive clinical course and the rapid expansion of the lesion observed in some rare cases of solitary EG. This is the third case-report of calvarial EG characterized by Ki-67 nuclear antigen expression.
Subject(s)
Dura Mater , Eosinophilic Granuloma , Histiocytosis, Langerhans-Cell , Ki-67 Antigen/metabolism , Skull , Dura Mater/metabolism , Dura Mater/pathology , Dura Mater/surgery , Eosinophilic Granuloma/metabolism , Eosinophilic Granuloma/pathology , Eosinophilic Granuloma/surgery , Histiocytosis, Langerhans-Cell/metabolism , Histiocytosis, Langerhans-Cell/pathology , Histiocytosis, Langerhans-Cell/surgery , Humans , Immunohistochemistry , Male , Skull/metabolism , Skull/pathology , Skull/surgery , Young AdultABSTRACT
The interhemispheric subdural hematomas (ISHs) are located along the whole interhemispheric scissure. The ISHs are a rare complication of head traumas. Possible predisposing factors such as coagulopathies, alcohol abuse or anticoagulant therapy are favouring factors. ISHs are rarely accompanied by changes in consciousness and it usually manifests itself with signs of "Falx Syndrome" (controlateral monoparesis of lower extremity or controlateral hemiparesis with lower limb weakness predominating). The treatment can consist of conservative observation or craniotomy and is dictated by the neurological evolution. In literature are described 140 cases since 1940 including our two conservatively managed patients. The salient aspects of ISHs are discussed in an analysis of the pertinent literature.
Subject(s)
Antihypertensive Agents/therapeutic use , Aspirin/therapeutic use , Hematoma, Subdural, Intracranial/drug therapy , Warfarin/therapeutic use , Aged , Aged, 80 and over , Anticoagulants/therapeutic use , Female , Hematoma, Subdural, Intracranial/diagnostic imaging , Humans , Platelet Aggregation Inhibitors/therapeutic use , RadiographyABSTRACT
The Authors present a case of rare elbow localization of schwannoma of the median nerve, in 42 year old woman. The surgical treatment and the short follow-up are presented.
Subject(s)
Elbow , Median Neuropathy/surgery , Neurilemmoma/surgery , Peripheral Nervous System Neoplasms/surgery , Adult , Elbow/innervation , Female , Follow-Up Studies , Humans , Median NerveABSTRACT
OBJECTIVES: To evaluate PTX3 feasibility to provide a prognostic tool in PMR clinical practice. METHODS: Circulating PTX3 levels were measured in 93 PMR patients at disease onset and during corticosteroid therapy and in 46 normal controls (NC) by ELISA. RESULTS: No difference in PTX3 concentrations was observed between NC and PMR either at disease onset and during follow-up or between groups of patients defined according to the presence of recurrence/relapse. CONCLUSIONS: PTX3 serum levels do not increase significantly in active PMR. Further studies on patients with giant-cell arteritis could evaluate whether large vessel involvement may be associated to increased PTX3 levels.
Subject(s)
C-Reactive Protein/analysis , Glucocorticoids/therapeutic use , Polymyalgia Rheumatica/blood , Polymyalgia Rheumatica/diagnosis , Serum Amyloid P-Component/analysis , Aged , Aged, 80 and over , Biomarkers/blood , Enzyme-Linked Immunosorbent Assay , Female , Humans , Male , Middle Aged , Polymyalgia Rheumatica/drug therapy , Prognosis , Prospective Studies , RecurrenceABSTRACT
AIM: Late cerebral radiation necrosis (LCR) is a serious complication of radiation treatment for brain tumors. This study investigates the diagnosis and management of patients with late clinical and neuroradiological cerebral radionecrosis after primary removal of brain neoplasm. The authors discuss the clinical features and long-term outcome of 21 patients with late cerebral radionecrosis and emphasize the importance of surgical and medical therapy. METHODS: Twenty-one patients with brain tumor treated by surgical resection or brain biopsy alone after radiotherapy during follow-up developed radionecrosis. The magnetic resonance imaging (MRI), surgical and clinical findings of these patients with radionecrosis are reviewed. RESULTS: MRI showed radionecrosis in 21 patients, 9 of which had undergone craniotomy for lesion removal. CONCLUSION: Late radionecrosis is infrequent following radiation therapy and may simulate tumor recurrence on MRI scans. From the authors' experience it is evident that, once begun, radiation treatment of neoplastic lesions can lead to complications such as late cerebral radionecrosis which often require surgical treatment. As correct diagnosis is necessary for appropriate treatment, a fair balance needs to be struck when considering ionizing radiation, medical therapy, surgery and diagnostic imaging.
Subject(s)
Brain Neoplasms/pathology , Brain Neoplasms/radiotherapy , Neoplasms, Radiation-Induced/pathology , Radiation Injuries/pathology , Radiotherapy/adverse effects , Adolescent , Adult , Aged , Biopsy , Brain Neoplasms/surgery , Craniotomy , Diagnosis, Differential , Female , Follow-Up Studies , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Necrosis , Neoplasm Recurrence, Local/pathology , Neoplasms, Radiation-Induced/surgery , Postoperative PeriodABSTRACT
UNLABELLED: Pentraxin 3 (PTX3) is an acute phase protein strongly expressed by advanced atherosclerotic lesions. We investigated (a) PTX3 expression and secretion in subcutaneous adipose tissue (SAT) and omental visceral adipose tissue (VAT) obtained from 21 obese (37.4+/-8.15 yr) and 10 normal weight subjects (43.7+/-11.07 yr) and (b) the relationships of adipose PTX3 with tumour necrosis factor alpha (TNFalpha) and adiponectin expression and with cardiometabolic risk factors. Real-time PCR was used to quantify specific mRNA for PTX3, CD68 (macrophage marker), TNFalpha and adiponectin. Fresh adipose tissue was cultured and PTX3 measured in the medium. Serum insulin, glucose, HDL and LDL cholesterol, triglycerides, C-reactive protein (CRP), fibrinogen, adiponectin, TNFalpha and PTX3 were measured. PTX3 expression was similar in the two fat compartments and tended to be higher in obese than in normal weight subjects in VAT only (p=0.05). CD68 and PTX3 expressions were correlated with each other in SAT but not in VAT. After adjustment for age and sex, VAT-PTX3 expression and release were correlated with VAT-TNFalpha expression (p<0.01 for both) and with LDL/HDL ratio (p<0.01 and p<0.001). VAT-PTX3 expression was also correlated with BMI, triglycerides, CRP, fibrinogen and adiponectin (p<0.05 for all). In the multivariate analysis with VAT-PTX3 RNA levels as dependent variable, LDL/HDL ratio and fibrinogen remained independently associated with VAT-PTX3 expression (p<0.01 for both). These associations were not seen within SAT. CONCLUSIONS: Human adipose tissue expresses and releases PTX3 likely under TNFalpha control. VAT production of PTX3 seems to contribute to the mechanisms underlying the development of atherosclerosis.
Subject(s)
Atherosclerosis/epidemiology , Atherosclerosis/genetics , C-Reactive Protein/genetics , Intra-Abdominal Fat/physiology , Serum Amyloid P-Component/genetics , Adipocytes/physiology , Adiponectin/metabolism , Adult , Antigens, CD/genetics , Antigens, Differentiation, Myelomonocytic/genetics , C-Reactive Protein/metabolism , Female , Gene Expression/physiology , Genetic Predisposition to Disease/epidemiology , Humans , Intra-Abdominal Fat/cytology , Lipids/blood , Male , Middle Aged , Obesity/epidemiology , Obesity/genetics , Risk Factors , Serum Amyloid P-Component/metabolism , Stem Cells/physiologyABSTRACT
The authors report about a case of the endovascular treatment of a pial arteriovenous malformation (AVM). The lesion was located on the conus medullaris. This injury is a rare spinal AVM. The diagnostic management and surgical treatment was chosen with a collaboration between neurosurgeons and neuroradiologists. The diagnostic management was based on clinical validation and magnetic resonance with angiographic technique as a gold standard. With regard to the surgical treatment of spinal AVM, endovascular and radiotherapy is a decision which should be taken multidisciplinarily. The treatment is crucial in resolving this lesion. The authors describe the case of a 38-year-old girl with clinical findings of progressive radiculomedullary ischemic process caused by the presence of spinal AVM. The angiographic images showed a pial AVM of the conus medullaris fed by an anterior radiculomedullary artery (Adamckiewiz artery) originated from a left T11 dorsospinal artery and by a posterior radiculopial artery originated from the left L1 artery. The draining veins were posterior pial veins, and accessory anterior subpial veins. Even if the first treatment of a pial arteriovenous malformation (AVM) of conus medullaris can be the surgical treatment for posterior localization, a neurointerventional angiographic and modern materials make it possible to reach pial AVMS of conus medullaris avoiding surgery. The authors describe a successful treatment of conus medullaris arteriovenous malformation with a one session of superselective embolization.
Subject(s)
Arteriovenous Malformations/therapy , Pia Mater/blood supply , Embolization, Therapeutic , Female , Humans , Lumbar Vertebrae/pathology , Middle Aged , Pia Mater/pathology , Spinal Cord/blood supply , Thoracic Vertebrae/pathologyABSTRACT
The treatment of chronic subdural hematoma (CSDH) was developed through a wide range of methods and technique. The excellent surgical treatment of CSDH is still controversial. The authors report a case of chronic subdural hematoma in a patient with antibodies antiphospholipidis syndrome (S. of Hughes). Antiphospholipid syndrome is characterized by arterial or venous thrombosis, and the presence of antiphospholipid antibodies (APL). APL are considered to be a cause of an acquired hypercoagulable state leading to stroke and transient ischemic attack (TIA).
Subject(s)
Antiphospholipid Syndrome/complications , Hematoma, Subdural, Chronic/etiology , Hematoma, Subdural, Intracranial/etiology , Female , Hematoma, Subdural, Chronic/pathology , Hematoma, Subdural, Chronic/surgery , Hematoma, Subdural, Intracranial/pathology , Hematoma, Subdural, Intracranial/surgery , Humans , Middle Aged , Neurosurgical Procedures , Tomography, X-Ray ComputedABSTRACT
Hsp60, a mitochondrial chaperonin highly conserved during evolution, has been found elevated in the cytosol of cancer cells, both in vivo and in vitro, but its role in determining apoptosis during oxidative stress (OS) has not yet been fully elucidated. The aim of the present work was to study the effects of OS on Hsp60 levels and its interactions with procaspase- 3 (p-C3) and p53 in tumor cells. NCI-H292 (mucoepidermoid carcinoma) cells were exposed to various concentrations of hydrogen peroxide (H2O2) for 24 hours. Cell viability was determined by Trypan blue and MTT assays. DNA damage was assessed by the Comet assay, and apoptosis was measured by the AnnexinV cytofluorimetric test. Exposure to increasing concentrations of H2O2 resulted in a reduction of cell viability, DNA damage, and early apoptotic phenomena. Hsp60, p-C3, p53, and p21 were assessed by Western blotting and immunocytochemistry before and after OS. Hsp60 and p-C3 were present before and after OS induction. Immunoprecipitation experiments showed an Hsp60/p-C3 complex before OS that persisted after it, while an Hsp60/p53 complex was not detected in either condition. The presence of wild type (wt) p53 was confirmed by RT-PCR, and p21 detection suggested p53 activation after OS. We postulate that, although OS may induce early apoptosis in NCI-H292 cells, Hsp60 exerts an anti-apoptotic effect in these cells and, by extension, it may do so in other cancer cells.
Subject(s)
Carcinoma, Mucoepidermoid/metabolism , Caspase 3/metabolism , Chaperonin 60/metabolism , Lung Neoplasms/metabolism , Oxidative Stress , Apoptosis/drug effects , Blotting, Western , Carcinoma, Mucoepidermoid/drug therapy , Carcinoma, Mucoepidermoid/pathology , Cell Line, Tumor , Cell Survival/drug effects , Comet Assay , DNA/drug effects , DNA Damage , Formazans/metabolism , Gene Expression/drug effects , Humans , Hydrogen Peroxide/pharmacology , Immunohistochemistry , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Tetrazolium Salts/metabolism , Trypan Blue/metabolism , Tumor Suppressor Protein p53/biosynthesis , Tumor Suppressor Protein p53/geneticsABSTRACT
During embryonic development, a pool of cells may become a reserve of undifferentiated cells, the embryo-stolen adult stem cells (ESASC). ESASC may be responsible for adult tissue homeostasis, as well as disease development. Transdifferentiation is a sort of reprogramming of ESASC from one germ layer-derived tissue towards another. Transdifferentiation has been described to take place from mesoderm to ectodermal- or endodermal-derived tissues and viceversa but not from ectodermal- to endodermal-derived tissues. We hypothesise that two different populations of ESASC could exist, the first ecto/mesoblast-committed and the second endo/mesoblast-committed. If confirmed, this hypothesis could lead to new studies on the molecular mechanisms of cell differentiation and to a better understanding of the pathogenesis of a number of diseases.
Subject(s)
Adult Stem Cells/cytology , Adult Stem Cells/physiology , Embryo, Mammalian/cytology , Stem Cell Transplantation , Wounds and Injuries/therapy , Adult , Cell Differentiation , Cell Lineage , Embryo, Mammalian/physiology , Humans , Mesoderm/cytology , Mesoderm/physiologyABSTRACT
INTRODUCTION: Morphological anomalies of the extracranial internal carotid artery (ICA) cause symptomatic cerebrovascular insufficiency in 4-16% of the cases. The aim of the present study is to evaluate macroscopic and microscopic features of a group of extracranial ICA anomalies, specifically kinking, coiling, and tortuosity, eventually affecting the surgical approach. MATERIALS AND METHODS: From January 2003 to December 2005, 10 out of 169 (6%) revascularized patients (pts) were operated upon because of an ICA anomaly. They were all but two symptomatics. Seven pts were treated by ICA transection and end-to-side reimplantation of the ICA at the level of the carotid bulb; three pts were treated by ICA resection and end-to-end anastomosis. In all the cases a segment of ICA was resected; in three cases one more segment was also obtained from a common carotid artery (CCA) and these specimens were histologically examined. Patients were followed-up through a 3-year period. RESULTS: No pts died and none suffered of neurologic events. Duplex scan and arteriographic postoperative control showed the correct surgical reconstruction. Matching preoperative clinical findings with presence or absence of significant atherosclerotic stenotic lesion, we found out a positive cerebral CT in one pt (20%) in both groups; fluent neurological deficit was preeminent in pts with pure ICA anomalies (40% vs. 0%) (P = 0.2); pts with pure ICA anomalies were significantly younger than 65 years old (80% vs. 0%) (P = 0.03) and males were more involved by pure ICA anomalies (60% vs. 40%) (P = 0.1). The histological examination of ICA specimens showed a reduction of elastic fibers and muscular cells with a compensative increase of connective fibers. CONCLUSIONS: At our knowledge this is the first study focused on ICA anomalies like kinking, coiling, and tortuosity, comparing histologic features of CCA and ICA specimens coming from the same affected carotid axis. Our results, although preliminary, show elastic and muscular tissue substituted by loose connective tissue, configuring a metaplasia of tunica media limited to the ICA. Our hypothesis is that extracranial ICA, being a segment of transition between an elastic vessel (CCA) and a muscular vessel (intracranial ICA), is particularly subject to metaplastic transformation, analogously to other transition zones in human body. Our purpose is now to confirm by ultrastructural and molecular biology techniques, in a wider series, the presence of this metaplasia, since this could condition also the revascularization techniques.
Subject(s)
Carotid Artery Diseases/surgery , Carotid Artery, Internal/abnormalities , Age Factors , Aged , Aged, 80 and over , Carotid Artery, Internal/diagnostic imaging , Carotid Artery, Internal/surgery , Female , Follow-Up Studies , Humans , Male , Metaplasia , Middle Aged , Sex Factors , Tomography, X-Ray Computed/methodsABSTRACT
OBJECTIVE: PTX3 is a secreted molecule which consists of a C-terminal domain similar to classical pentraxins (e.g. C-reactive protein) and of an unrelated N-terminal domain. Unlike the classical pentraxins, PTX3 is expressed in response to IL-1beta and TNF-alpha but not to IL-6. The present study was designed to investigate the expression of PTX3 in normal and scleroderma fibroblasts. METHODS: Normal and SSc fibroblasts were cultured in the presence and absence of inflammatory cytokines. PTX3 mRNA expression in fibroblasts was evaluated by Northern analysis. PTX3 protein levels in fibroblast culture medium were estimated by ELISA. RESULTS: Normal fibroblasts were induced to express high levels of P7X3 mRNA by IL-1beta and TNF-alpha but not by other cytokines or growth factors. Scleroderma fibroblasts, unlike normal fibroblasts, constitutively expressed high levels of PTX3 in the absence of deliberate stimulation. The constitutive expression of PTX3 in SSc fibroblasts was not modified by anti-TNF-alpha antibodies or IL-1 receptor antagonist. In contrast, IFN-gamma and TGF-beta inhibited the constitutive but not the stimulated expression of PTX3 in SSc fibroblasts. CONCLUSIONS: PTX3 is a main feature of activated scleroderma fibroblasts.
Subject(s)
C-Reactive Protein/biosynthesis , Fibroblasts/metabolism , Scleroderma, Systemic/metabolism , Serum Amyloid P-Component/biosynthesis , Cell Culture Techniques , Cytokines/metabolism , Humans , Interferon-gamma/metabolism , Interleukin-1/metabolism , RNA, Messenger/biosynthesis , Transforming Growth Factor beta , Tumor Necrosis Factor-alpha/metabolismABSTRACT
Human natural killer (NK) cells constitutively express the beta- and gamma-chains of the interleukin 2 (IL-2)/IL-15 receptor, and both IL-2 and IL-15 are able to activate NK cell proliferation and cytotoxicity. When IL-2-primed human NK cells are exposed to sensitive targets (i.e. K562) they undergo apoptosis mediated by the beta(2)-integrin CD18. Here, we demonstrate that: (i) endothelial cells, similar to K562 tumour target cells, induce apoptosis of IL-2-primed NK cells; (ii) endothelial- and K562 cell-induced apoptosis is significantly lower in IL-15 than in IL-2-stimulated NK cells; (iii) a critical role in the apoptosis of IL-2-primed NK cells is played by the alpha-chain of the IL-2 receptor. Our data show for the first time that IL-2-activated NK cells can die by apoptosis upon contact with the vascular endothelium, which is a necessary step for their extravasation, with a direct pathophysiological relevance on the strategy of adoptive immunotherapy of cancer. On the other hand, IL-15, although generating a similar level of activation of NK cells, largely prevents their apoptotic fate. Therefore, IL-15 produced early in the immune response, when T cells are not yet activated, generates lymphokine-activated killer cells that are efficient killers relatively protected from apoptosis. Once activated, T cells produce IL-2 that overcomes the effect of IL-15 on NK cells, paving the way for their death by apoptosis.
Subject(s)
Apoptosis/immunology , Endothelium, Vascular/immunology , Interleukin-15/immunology , Interleukin-2/immunology , Killer Cells, Natural/immunology , Cell Culture Techniques , Cytotoxicity, Immunologic , Dose-Response Relationship, Immunologic , Endothelium, Vascular/cytology , Humans , K562 Cells/immunology , Killer Cells, Lymphokine-Activated/immunology , Lymphocyte Activation/immunologyABSTRACT
Pentraxin 3, a prototypic long pentraxin, is induced by proinflammatory signals in the brain. Inflammatory cytokines are rapidly induced in glia by epileptic activity. We show that pentraxin 3 immunoreactivity and mRNA are enhanced in the rat forebrain above undetectable control levels by limbic seizures with a dual pattern of induction. Within 6 h from seizure onset, pentraxin 3 immunoreactivity was increased in astrocytes. Eighteen to 48 h later, specific neuronal populations and leucocytes were strongly immunoreactive only in areas of neurodegeneration. This staining was abolished when neuronal cell loss, but not seizures, was prevented by blocking N-methyl-D-aspartate receptors. Pentraxin 3 -/- mice had a more widespread seizure-related neuronal damage in the forebrain than their wild-type littermates although both groups had similar epileptic activity. Our results provide evidence that pentraxin 3 is synthesized in brain after seizures and may exert a protective role in seizure-induced neurodegeneration.