Search results for: opacity
10 European Project Meter Matters in Sports: Fostering Criteria for Inclusion through Sport
Authors: Maria Campos, Alain Massart, Hugo Sarmento
Abstract:
The Meter Matters Erasmus Sport European Project (ID: 101050372) explores the field of social inclusion in and through sports with the aim of a) proposing appropriate criteria for co-funding sports programs involving people with intellectual and developmental disabilities and other more vulnerable people, primarily in mainstream sports organizations and b) proposing a model for co-funding social inclusion in and through sports at the national level. This European project (2022-2024) involves 6 partners from 3 countries: Univerza V Ljubljani – coordinator and Drustvo Specialna Olimpiada Slovenije (Slovenia); Magyar Specialis Olimpia Szovetseg and Magyar Testnevelesi Es Sporttudomanyi Egyetem (Hungary) and APPDA Coimbra - Associação Portuguesa para as Perturbações do Desenvolvimento e Autismo and Universidade De Coimbra, Faculty of Sport Sciences and Physical Education (Portugal). Equal involvement of all people in sports activities is, in terms of national and international guidelines, enshrined in some conventions and strategies in the field of sports, as well as human rights, social security, physical and mental health, architecture, environment and public administration. However, there is a gap between the practice and EU guidelines in terms of sustainable support for socially inclusive sports programs in the form of co-funding by state and local (municipal) resources. We observe considerable opacity in the regulation of the field. Given that there are both relevant programs and inclusive legislation and policies, we believe that the reason for the missing article is reflected in the undeveloped criteria for measuring social inclusion in sports. Major sports programs are usually co-funded based on crowds (number of involved athletes) and performance (sports score). In the field of social inclusion in sports, the criteria cannot be the same, as it is a smaller population. Therefore, the goals of inclusion in sports should not be the focused on competitive results but on opening equal opportunities for all, regardless of their psychophysical abilities. In the Meter Matters program, we are searching for criteria for co-funding social inclusion in sports through focus groups with coaches, social workers, psychologists and others professionals involved in inclusive sports programs in regular sports clubs and with athletes and their parents or guardians. Moreover, experts in the field of social inclusion in sports were also interviewed. Based on the proposals for measuring social inclusion in sports, we developed a model for co-funding socially inclusive sports programs.Keywords: European project, meter matters, inclusion, sport
Procedia PDF Downloads 1139 The Development and Testing of a Small Scale Dry Electrostatic Precipitator for the Removal of Particulate Matter
Authors: Derek Wardle, Tarik Al-Shemmeri, Neil Packer
Abstract:
This paper presents a small tube/wire type electrostatic precipitator (ESP). In the ESPs present form, particle charging and collecting voltages and airflow rates were individually varied throughout 200 ambient temperature test runs ranging from 10 to 30 kV in increments on 5 kV and 0.5 m/s to 1.5 m/s, respectively. It was repeatedly observed that, at input air velocities of between 0.5 and 0.9 m/s and voltage settings of 20 kV to 30 kV, the collection efficiency remained above 95%. The outcomes of preliminary tests at combustion flue temperatures are, at present, inconclusive although indications are that there is little or no drop in comparable performance during ideal test conditions. A limited set of similar tests was carried out during which the collecting electrode was grounded, having been disconnected from the static generator. The collecting efficiency fell significantly, and for that reason, this approach was not pursued further. The collecting efficiencies during ambient temperature tests were determined by mass balance between incoming and outgoing dry PM. The efficiencies of combustion temperature runs are determined by analysing the difference in opacity of the flue gas at inlet and outlet compared to a reference light source. In addition, an array of Leit tabs (carbon coated, electrically conductive adhesive discs) was placed at inlet and outlet for a number of four-day continuous ambient temperature runs. Analysis of the discs’ contamination was carried out using scanning electron microscopy and ImageJ computer software that confirmed collection efficiencies of over 99% which gave unequivocal support to all the previous tests. The average efficiency for these runs was 99.409%. Emissions collected from a woody biomass combustion unit, classified to a diameter of 100 µm, were used in all ambient temperature trials test runs apart from two which collected airborne dust from within the laboratory. Sawdust and wood pellets were chosen for laboratory and field combustion trials. Video recordings were made of three ambient temperature test runs in which the smoke from a wood smoke generator was drawn through the precipitator. Although these runs were visual indicators only, with no objective other than to display, they provided a strong argument for the device’s claimed efficiency, as no emissions were visible at exit when energised. The theoretical performance of ESPs, when applied to the geometry and configuration of the tested model, was compared to the actual performance and was shown to be in good agreement with it.Keywords: electrostatic precipitators, air quality, particulates emissions, electron microscopy, image j
Procedia PDF Downloads 2538 A Disappearing Radiolucency of the Mandible Caused by Inadvertent Trauma Following IMF Screw Placement
Authors: Anna Ghosh, Dominic Shields, Ceri McIntosh, Stephen Crank
Abstract:
A 29-year-old male was a referral to the maxillofacial unit following a referral from his general dental practitioner via a routine pathway regarding a large periapical lesion on the LR4 with root resorption. The patient was asymptomatic, the LR4 vital and unrestored, and this was an incidental finding at a routine check-up. The patient's past medical history was unremarkable. Examination revealed no extra or intra-oral pathology and non-mobile teeth. No focal neurology was detected. An orthopantogram demonstrated a well-defined unilocular corticated radiolucency associated with the LR4. The root appeared shortened with the radiolucency between the root and a radio-opacity, possibly representing the displacement of the apical tip of the tooth. It was recommended that the referring general practitioner should proceed with orthograde root canal therapy, after which time exploration, enucleation, and retrograde root filling of the LR4 would be carried out by a maxillofacial unit. The patient was reviewed six months later where, due to the COVID-19 pandemic, the patient had been unable to access general dental services for the root canal treatment. He was still entirely asymptomatic. A one-year review was planned in the hope this would allow time for the orthograde root canal therapy to be completed. At this review, the orthograde root canal therapy had still not been completed. Interestingly, a repeat orthopantogram revealed a significant reduction in size with good bony infill and a significant reduction in the size of the lesion. Due to the ongoing delays with primary care dental therapy, the patient was subsequently internally referred to the restorative dentistry department for care. The patient was seen again by oral and maxillo-facial surgery in mid-2022 where he still reports this tooth as asymptomatic with no focal neurology. The patient's history was fully reviewed, and noted that 15 years previously, the patient underwent open reduction and internal fixation of a left angle of mandible fracture. Temporary IMF involving IMF screws and fixation wires were employed to maintain occlusion during plating and subsequently removed post-operatively. It is proposed that the radiolucency was, as a result of the IMF screw placement, penetrating the LR4 root resulting in resorption of the tooth root and development of a radiolucency. This case highlights the importance of careful screw size and physical site location, and placement of IMF screws, as there can be permeant damage to a patient’s dentition.Keywords: facial trauma, inter-maxillary fixation, mandibular radiolucency, oral and maxillo-facial surgery
Procedia PDF Downloads 1377 Blade-Coating Deposition of Semiconducting Polymer Thin Films: Light-To-Heat Converters
Authors: M. Lehtihet, S. Rosado, C. Pradère, J. Leng
Abstract:
Poly(3,4-ethylene dioxythiophene) polystyrene sulfonate (PEDOT: PSS), is a polymer mixture well-known for its semiconducting properties and is widely used in the coating industry for its visible transparency and high electronic conductivity (up to 4600 S/cm) as a transparent non-metallic electrode and in organic light-emitting diodes (OLED). It also possesses strong absorption properties in the Near Infra-Red (NIR) range (λ ranging between 900 nm to 2.5 µm). In the present work, we take advantage of this absorption to explore its potential use as a transparent light-to-heat converter. PEDOT: PSS aqueous dispersions are deposited onto a glass substrate using a blade-coating technique in order to produce uniform coatings with controlled thicknesses ranging in ≈ 400 nm to 2 µm. Blade-coating technique allows us good control of the deposit thickness and uniformity by the tuning of several experimental conditions (blade velocity, evaporation rate, temperature, etc…). This liquid coating technique is a well-known, non-expensive technique to realize thin film coatings on various substrates. For coatings on glass substrates destined to solar insulation applications, the ideal coating would be made of a material able to transmit all the visible range while reflecting the NIR range perfectly, but materials possessing similar properties still have unsatisfactory opacity in the visible too (for example, titanium dioxide nanoparticles). NIR absorbing thin films is a more realistic alternative for such an application. Under solar illumination, PEDOT: PSS thin films heat up due to absorption of NIR light and thus act as planar heaters while maintaining good transparency in the visible range. Whereas they screen some NIR radiation, they also generate heat which is then conducted into the substrate that re-emits this energy by thermal emission in every direction. In order to quantify the heating power of these coatings, a sample (coating on glass) is placed in a black enclosure and illuminated with a solar simulator, a lamp emitting a calibrated radiation very similar to the solar spectrum. The temperature of the rear face of the substrate is measured in real-time using thermocouples and a black-painted Peltier sensor measures the total entering flux (sum of transmitted and re-emitted fluxes). The heating power density of the thin films is estimated from a model of the thin film/glass substrate describing the system, and we estimate the Solar Heat Gain Coefficient (SHGC) to quantify the light-to-heat conversion efficiency of such systems. Eventually, the effect of additives such as dimethyl sulfoxide (DMSO) or optical scatterers (particles) on the performances are also studied, as the first one can alter the IR absorption properties of PEDOT: PSS drastically and the second one can increase the apparent optical path of light within the thin film material.Keywords: PEDOT: PSS, blade-coating, heat, thin-film, Solar spectrum
Procedia PDF Downloads 1646 Injunctions, Disjunctions, Remnants: The Reverse of Unity
Authors: Igor Guatelli
Abstract:
The universe of aesthetic perception entails impasses about sensitive divergences that each text or visual object may be subjected to. If approached through intertextuality that is not based on the misleading notion of kinships or similarities a priori admissible, the possibility of anachronistic, heterogeneous - and non-diachronic - assemblies can enhance the emergence of interval movements, intermediate, and conflicting, conducive to a method of reading, interpreting, and assigning meaning that escapes the rigid antinomies of the mere being and non-being of things. In negative, they operate in a relationship built by the lack of an adjusted meaning set by their positive existences, with no remainders; the generated interval becomes the remnant of each of them; it is the opening that obscures the stable positions of each one. Without the negative of absence, of that which is always missing or must be missing in a text, concept, or image made positive by history, nothing is perceived beyond what has been already given. Pairings or binary oppositions cannot lead only to functional syntheses; on the contrary, methodological disturbances accumulated by the approximation of signs and entities can initiate a process of becoming as an opening to an unforeseen other, transformation until a moment when the difficulties of [re]conciliation become the mainstay of a future of that sign/entity, not envisioned a priori. A counter-history can emerge from these unprecedented, misadjusted approaches, beginnings of unassigned injunctions and disjunctions, in short, difficult alliances that open cracks in a supposedly cohesive history, chained in its apparent linearity with no remains, understood as a categorical historical imperative. Interstices are minority fields that, because of their opening, are capable of causing opacity in that which, apparently, presents itself with irreducible clarity. Resulting from an incomplete and maladjusted [at the least dual] marriage between the signs/entities that originate them, this interval may destabilize and cause disorder in these entities and their own meanings. The interstitials offer a hyphenated relationship: a simultaneous union and separation, a spacing between the entity’s identity and its otherness or, alterity. One and the other may no longer be seen without the crack or fissure that now separates them, uniting, by a space-time lapse. Ontological, semantic shifts are caused by this fissure, an absence between one and the other, one with and against the other. Based on an improbable approximation between some conceptual and semantic shifts within the design production of architect Rem Koolhaas and the textual production of the philosopher Jacques Derrida, this article questions the notion of unity, coherence, affinity, and complementarity in the process of construction of thought from these ontological, epistemological, and semiological fissures that rattle the signs/entities and their stable meanings. Fissures in a thought that is considered coherent, cohesive, formatted are the negativity that constitutes the interstices that allow us to move towards what still remains as non-identity, which allows us to begin another story.Keywords: clearing, interstice, negative, remnant, spectrum
Procedia PDF Downloads 1345 Rendering Religious References in English: Naguib Mahfouz in the Arabic as a Foreign Language Classroom
Authors: Shereen Yehia El Ezabi
Abstract:
The transition from the advanced to the superior level of Arabic proficiency is widely known to pose considerable challenges for English speaking students of Arabic as a Foreign Language (AFL). Apart from the increasing complexity of the grammar at this juncture, together with the sprawling vocabulary, to name but two of those challenges, there is also the somewhat less studied hurdle along the way to superior level proficiency, namely, the seeming opacity of many aspects of Arab/ic culture to such learners. This presentation tackles one specific dimension of such issues: religious references in literary texts. It illustrates how carefully constructed translation activities may be used to expand and deepen students’ understanding and use of them. This is shown to be vital for making the leap to the desired competency, given that such elements, as reflected in customs, traditions, institutions, worldviews, and formulaic expressions lie at the very core of Arabic culture and, as such, pervade all modes and levels of Arabic discourse. A short story from the collection “Stories from Our Alley”, by preeminent novelist Naguib Mahfouz is selected for use in this context, being particularly replete with such religious references, of which religious expressions will form the focus of the presentation. As a miniature literary work, it provides an organic whole, so to speak, within which to explore with the class the most precise denotation, as well as the subtlest connotation of each expression in an effort to reach the ‘best’ English rendering. The term ‘best’ refers to approximating the meaning in its full complexity from the source text, in this case Arabic, to the target text, English, according to the concept of equivalence in translation theory. The presentation will show how such a process generates the sort of thorough discussion and close text analysis which allows students to gain valuable insight into this central idiom of Arabic. A variety of translation methods will be highlighted, gleaned from the presenter’s extensive work with advanced/superior students in the Center for Arabic Study Abroad (CASA) program at the American University in Cairo. These begin with the literal rendering of expressions, with the purpose of reinforcing vocabulary learning and practicing the rules of derivational morphology as they form each word, since the larger context remains that of an AFL class, as opposed to a translation skills program. However, departures from the literal approach are subsequently explored by degrees, moving along the spectrum of functional and pragmatic freer translations in order to transmit the ‘real’ meaning in readable English to the target audience- no matter how culture/religion specific the expression- while remaining faithful to the original. Samples from students’ work pre and post discussion will be shared, demonstrating how class consensus is formed as to the final English rendering, proposed as the closest match to the Arabic, and shown to be the result of the above activities. Finally, a few examples of translation work which students have gone on to publish will be shared to corroborate the effectiveness of this teaching practice.Keywords: superior level proficiency in Arabic as a foreign language, teaching Arabic as a foreign language, teaching idiomatic expressions, translation in foreign language teaching
Procedia PDF Downloads 1994 Mycophenolate Mofetil Increases Mucin Expression in Primary Cultures of Oral Mucosal Epithelial Cells for Application in Limbal Stem Cell Deficiency
Authors: Sandeep Kumar Agrawal, Aditi Bhattacharya, Janvie Manhas, Krushna Bhatt, Yatin Kholakiya, Nupur Khera, Ajoy Roychoudhury, Sudip Sen
Abstract:
Autologous cultured explants of human oral mucosal epithelial cells (OMEC) are a potential therapeutic modality for limbal stem cell deficiency (LSCD). Injury or inflammation of the ocular surface in the form of burns, chemicals, Stevens Johnson syndrome, ocular cicatricial pemphigoid etc. can lead to destruction and deficiency of limbal stem cells. LSCD manifests in the form of severe ocular surface diseases (OSD) characterized by persistent and recurrent epithelial defects, conjuntivalisation and neovascularisation of the corneal surface, scarring and ultimately opacity and blindness. Most of the cases of OSD are associated with severe dry eye pertaining to diminished mucin and aqueous secretion. Mycophenolate mofetil (MMF) has been shown to upregulate the mucin expression in conjunctival goblet cells in vitro. The aim of this study was to evaluate the effects of MMF on mucin expression in primary cultures of oral mucosal epithelial cells. With institutional ethics committee approval and written informed consent, thirty oral mucosal epithelial tissue samples were obtained from patients undergoing oral surgery for non-malignant conditions. OMEC were grown on human amniotic membrane (HAM, obtained from expecting mothers undergoing elective caesarean section) scaffold for 2 weeks in growth media containing DMEM & Ham’s F12 (1:1) with 10% FBS and growth factors. In vitro dosage of MMF was standardised by MTT assay. Analysis of stem cell markers was done using RT-PCR while mucin mRNA expression was quantified using RT-PCR and q-PCR before and after treating cultured OMEC with graded concentrations of MMF for 24 hours. Protein expression was validated using immunocytochemistry. Morphological studies revealed a confluent sheet of proliferating, stratified oral mucosal epithelial cells growing over the surface of HAM scaffold. The presence of progenitor stem cell markers (p63, p75, β1-Integrin and ABCG2) and cell surface associated mucins (MUC1, MUC15 and MUC16) were elucidated by RT-PCR. The mucin mRNA expression was found to be upregulated in MMF treated primary cultures of OMEC, compared to untreated controls as quantified by q-PCR with β-actin as internal reference gene. Increased MUC1 protein expression was validated by immunocytochemistry on representative samples. Our findings conclude that OMEC have the ability to form a multi-layered confluent sheet on the surface of HAM similar to a cornea, which is important for the reconstruction of the damaged ocular surface. Cultured OMEC has stem cell properties as demonstrated by stem cell markers. MMF can be a novel enhancer of mucin production in OMEC. It has the potential to improve dry eye in patients undergoing OMEC transplantation for bilateral OSD. Further clinical trials are required to establish the role of MMF in patients undergoing OMEC transplantation.Keywords: limbal stem cell deficiency, mycophenolate mofetil, mucin, ocular surface disease
Procedia PDF Downloads 3323 Pluripotent Stem Cells as Therapeutic Tools for Limbal Stem Cell Deficiencies and Drug Testing
Authors: Aberdam Edith, Sangari Linda, Petit Isabelle, Aberdam Daniel
Abstract:
Background and Rationale: Transparent avascularised cornea is essential for normal vision and depends on limbal stem cells (LSC) that reside between the cornea and the conjunctiva. Ocular burns or injuries may destroy the limbus, causing limbal stem cell deficiency (LSCD). The cornea becomes vascularised by invaded conjunctival cells, the stroma is scarring, resulting in corneal opacity and loss of vision. Grafted autologous limbus or cultivated autologous LCS can restore the vision, unless the two eyes are affected. Alternative cellular sources have been tested in the last decades, including oral mucosa or hair follicle epithelial cells. However, only partial success has been achieved by the use of these cells since they were not able to uniformly commit into corneal epithelial cells. Human pluripotent stem cells (iPSC) display both unlimited growth capacity and ability to differentiate into any cell type. Our goal was to design a standardized and reproducible protocol to produce transplantable autologous LSC from patients through cell reprogramming technology. Methodology: First, keratinocyte primary culture was established from a small number of plucked hair follicles of healthy donors. The resulting epithelial cells were reprogrammed into induced pluripotent stem cells (iPSCs) and further differentiate into corneal epithelial cells (CEC), according to a robust protocol that recapitulates the main step of corneal embryonic development. qRT-PCR analysis and immunofluorescent staining during the course of differentiation confirm the expression of stage specific markers of corneal embryonic lineage. First appear ectodermal progenitor-specific cytokeratins K8/K18, followed at day 7 by limbal-specific PAX6, TP63 and cytokeratins K5/K14. At day 15, K3/K12+-corneal cells are present. To amplify the iPSC-derived LSC (named COiPSC), intact small epithelial colonies were detached and cultivated in limbal cell-specific medium. In that culture conditions, the COiPSC can be frozen and thaw at any passage, while retaining their corneal characteristics for at least eight passages. To evaluate the potential of COiPSC as an alternative ocular toxicity model, COiPSC were treated at passage P0 to P4 with increasing amounts of SDS and Benzalkonium. Cell proliferation and apoptosis of treated cells was compared to LSC and the SV40-immortalized human corneal epithelial cell line (HCE) routinely used by cosmetological industrials. Of note, HCE are more resistant to toxicity than LSC. At P0, COiPSC were systematically more resistant to chemical toxicity than LSC and even to HCE. Remarkably, this behavior changed with passage since COiPSC at P2 became identical to LSC and thus closer to physiology than HCE. Comparative transcriptome analysis confirmed that COiPSC from P2 are similar to a mixture of LSC and CEC. Finally, by organotypic reconstitution assay, we demonstrated the ability of COiPSC to produce a 3D corneal epithelium on a stromal equivalent made of keratocytes. Conclusion: COiPSC could become valuable for two main applications: (1) an alternative robust tool to perform, in a reproducible and physiological manner, toxicity assays for cosmetic products and pharmacological tests of drugs. (2). COiPSC could become an alternative autologous source for cornea transplantation for LSCD.Keywords: Limbal stem cell deficiency, iPSC, cornea, limbal stem cells
Procedia PDF Downloads 4142 Consecration from the Margins: El Anatsui in Venice and the Turbine Hall
Authors: Jonathan Adeyemi
Abstract:
Context: This study focuses on El Anatsui and his global acclaim in the art world despite his origins from the global artworld’s margins. It addresses the disparities in the treatment between Western and non-Western artists and questions whether Anatsui’s consecration is a result of exoticism or the growing consensus on decolonization. Research Aim: The aim of this study is to investigate how El Anatsui achieved global acclaim from the margins of the art world and determine if his consecration represents a mark of decolonization or the typical Western desire for exoticism. Methodology: The study utilizes a case study approach, literature analysis, and in-depth interviews. The artist, the organizers of the Venice Biennale, the relevant curators at Tate Modern London, and the October Gallery in London, and other galleries in Nigeria, which represent the artist were interviewed for data collection. Findings: The study seeks to determine the authenticity of the growing consensus on decolonization, inclusion, and diversity in the global artistic field. Preliminary findings show that domestic socio-economic and political factors debilitated the mechanisms for local validation in Nigeria, weakening the domestic foundation for international engagement. However, alternative systems of exhibition, especially in London and the USA contributed critically to providing the initial international visibility, which formed the foundation for his global acclaim. Out of the 21 winners of the Golden Lion for Lifetime Achievement since its inception at the 47th Venice Biennale in 1997, American artists have dominated with 10 recipients, 8 recipients from Europe, 2 recipients from Africa (2007 and 2015) and 1 from Asia. This aligns with Bourdieu’s concept of cultural and economic capital, which prevented Africa countries from participation until recently. Moreover, while the average age of recipients is 76 years, Anatsui received the award at the age of 71, while Malick Sidibé (Mali) was awarded at 72. Thus, the Venice Biennale award for El Anatsui incline more towards a commitment to decolonisation than exoticism. Theoretical Importance: This study contributes to the field by examining the dynamics of the art world's monopoly of legitimation and the role of national, ethnicity and cultural differences in the promotion of artists. It aims to challenge the Westernized hierarchy of valorization and consecration in the art world. The research supports Bourdieu’s artistic field theory, which emphasises the importance of cultural, economic and social capital in determining agents’ position and access to the field resources (symbolic capital). Bourdieu also established that dominated agents can change their position in the field’s hierarchy either by establishing or navigating alternative systems. Data Collection and Analysis Procedures: The opacity of art world’s operations places the required information within the purview of the insiders (agents). Thus, the study collects data through in-depth interviews with relevant and purposively selected individuals and organizations. The data was/will be analyzed using qualitative methods, such as thematic analysis and content analysis. The interpretive analytical approach adopted facilitated the construction of meanings that may not be apparent in the data or responses. Questions Addressed: The study addresses how El Anatsui achieved global acclaim despite being from the margins, whether his consecration represents decolonization or exoticism, and the extent to which the global artistic field embraces decolonization, inclusion, and diversity. Conclusion: The study will contribute to knowledge by providing insights into the extent of commitment to decolonization, inclusion, and diversity in the global artistic field. It also shed light on the mechanisms behind El Anatsui's rise to global acclaim and challenge Western-dominated artistic hierarchies.Keywords: decolonisation, exorticism, artistic field, culture game
Procedia PDF Downloads 601 Amifostine Analogue, Drde-30, Attenuates Radiation-Induced Lung Injury in Mice
Authors: Aastha Arora, Vikas Bhuria, Saurabh Singh, Uma Pathak, Shweta Mathur, Puja P. Hazari, Rajat Sandhir, Ravi Soni, Anant N. Bhatt, Bilikere S. Dwarakanath
Abstract:
Radiotherapy is an effective curative and palliative option for patients with thoracic malignancies. However, lung injury, comprising of pneumonitis and fibrosis, remains a significant clin¬ical complication of thoracic radiation, thus making it a dose-limiting factor. Also, injury to the lung is often reported as part of multi-organ failure in victims of accidental radiation exposures. Radiation induced inflammatory response in the lung, characterized by leukocyte infiltration and vascular changes, is an important contributing factor for the injury. Therefore, countermeasure agents to attenuate radiation induced inflammatory response are considered as an important approach to prevent chronic lung damage. Although Amifostine, the widely used, FDA approved radio-protector, has been found to reduce the radiation induced pneumonitis during radiation therapy of non-small cell lung carcinoma, its application during mass and field exposure is limited due to associated toxicity and ineffectiveness with the oral administration. The amifostine analogue (DRDE-30) overcomes this limitation as it is orally effective in reducing the mortality of whole body irradiated mice. The current study was undertaken to investigate the potential of DRDE-30 to ameliorate radiation induced lung damage. DRDE-30 was administered intra-peritoneally, 30 minutes prior to 13.5 Gy thoracic (60Co-gamma) radiation in C57BL/6 mice. Broncheo- alveolar lavage fluid (BALF) and lung tissues were harvested at 12 and 24 weeks post irradiation for studying inflammatory and fibrotic markers. Lactate dehydrogenase (LDH) leakage, leukocyte count and protein content in BALF were used as parameters to evaluate lung vascular permeability. Inflammatory cell signaling (p38 phosphorylation) and anti-oxidant status (MnSOD and Catalase level) was assessed by Western blot, while X-ray CT scan, H & E staining and trichrome staining were done to study the lung architecture and collagen deposition. Irradiation of the lung increased the total protein content, LDH leakage and total leukocyte count in the BALF, reflecting endothelial barrier dysfunction. These disruptive effects were significantly abolished by DRDE-30, which appear to be linked to the DRDE-30 mediated abrogation of activation of the redox-sensitive pro- inflammatory signaling cascade, the MAPK pathway. Concurrent administration of DRDE-30 with radiation inhibited radiation-induced oxidative stress by strengthening the anti-oxidant defense system and abrogated p38 mitogen-activated protein kinase activation, which was associated with reduced vascular leak and macrophage recruitment to the lungs. Histopathological examination (by H & E staining) of the lung showed radiation-induced inflammation of the lungs, characterized by cellular infiltration, interstitial oedema, alveolar wall thickening, perivascular fibrosis and obstruction of alveolar spaces, which were all reduced by pre-administration of DRDE-30. Structural analysis with X-ray CT indicated lung architecture (linked to the degree of opacity) comparable to un-irradiated mice that correlated well with the lung morphology and reduced collagen deposition. Reduction in the radiation-induced inflammation and fibrosis brought about by DRDE-30 resulted in a profound increase in animal survival (72 % in the combination vs 24% with radiation) observed at the end of 24 weeks following irradiation. These findings establish the potential of the Amifostine analogue, DRDE-30, in reducing radiation induced pulmonary injury by attenuating the inflammatory and fibrotic responses.Keywords: amifostine, fibrosis, inflammation, lung injury radiation
Procedia PDF Downloads 510