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Author: Daniel Anibal Cantero Cajas Publisher: ISBN: Category : Biofilms Languages : en Pages : 422
Book Description
Chronic Rhinosinusitis (CRS) is the persistent and symptomatic inflammation of the mucosa of the nose and paranasal cavities. It is a prevalent condition severely affecting the quality of life of around 10% of the population in Western countries. Its pathogenesis involves environmental factors such as viruses or bacteria on predisposed hosts triggering local mucosal inflammation. Staphylococcus aureus (S. aureus) is the most common isolated bacterium in CRS and, when forming biofilms, increases its resistance to antibiotics, being correlated with recalcitrant cases and higher rates of mucosal inflammation. The local inflammation can be explained by virulence factors from S. aureus, and also by innate and adaptive immune mechanisms of the host immune response. Although some researchers have explored the late or adaptive immune response associated with S. aureus biofilms, less is known about the initial or innate immune response that S. aureus biofilms trigger in the mucosa. This thesis aimed to study part of the mucosal innate immune response to S. aureus biofilms. We have challenged human sinonasal tissues - from normal donors undergoing transnasal pituitary surgery - with S. aureus biofilms ex vivo using an explant model. This model mimics in vivo conditions because it allows biofilms to grow at the air-liquid interface. Also, the biofilm-mucosa interaction is more physiological than primary cell cultures, because the communication between different host cells is preserved in the explant model. After the interaction with S. aureus biofilms, explant tissues produced IL-6 and other cytokines polarised to a Th1/Th17 type of immune response. The observed Th1/Th17 immune response differs from previous reports in eosinophilic CRS patients with nasal polyps (CRSwNP) showing a predominant Th2 response. Apparently there is an evolution from early Th1/Th17 immune responses to late Th2 in S. aureus biofilm associated infections. The turning point between these two types of immune responses seems critical in CRS because it could explain the origin of the Th2 inflammation. In the future, the use of long-term animal models could help to illustrate the progression from an initial Th1/Th17 to a late Th2 type of immune response in the sinonasal mucosa. S. aureus biofilms also induced apoptosis in the mucosa as demonstrated by the up-regulation of cleaved caspase-3 in our settings. We also demonstrated the induction and activation of the Nod2 receptor and downstream pathway secondary to S. aureus biofilms. The Nod2 receptor recognises a small portion of peptidoglycan that is available during early phases of S. aureus biofilm formation. The role of Nod2 in CRS and biofilm infections should be evaluated in future studies. In conclusion, we demonstrated that early S. aureus biofilms induce a proinflammatory response in the sinonasal mucosa. This proinflammatory response seems to be crucial for biofilm attachment and persistence, and its modulation could represent an alternative to prevent S. aureus biofilm infections. Secreted staphylococcal products such as alpha ([alpha]) toxin and staphylococcal protein A (SpA) are two virulence factors critical during early biofilm growth. These proteins are also able to generate immune responses and represent targets for potential therapeutic intervention during biofilm infections in the sinonasal mucosa.
Author: Daniel Anibal Cantero Cajas Publisher: ISBN: Category : Biofilms Languages : en Pages : 422
Book Description
Chronic Rhinosinusitis (CRS) is the persistent and symptomatic inflammation of the mucosa of the nose and paranasal cavities. It is a prevalent condition severely affecting the quality of life of around 10% of the population in Western countries. Its pathogenesis involves environmental factors such as viruses or bacteria on predisposed hosts triggering local mucosal inflammation. Staphylococcus aureus (S. aureus) is the most common isolated bacterium in CRS and, when forming biofilms, increases its resistance to antibiotics, being correlated with recalcitrant cases and higher rates of mucosal inflammation. The local inflammation can be explained by virulence factors from S. aureus, and also by innate and adaptive immune mechanisms of the host immune response. Although some researchers have explored the late or adaptive immune response associated with S. aureus biofilms, less is known about the initial or innate immune response that S. aureus biofilms trigger in the mucosa. This thesis aimed to study part of the mucosal innate immune response to S. aureus biofilms. We have challenged human sinonasal tissues - from normal donors undergoing transnasal pituitary surgery - with S. aureus biofilms ex vivo using an explant model. This model mimics in vivo conditions because it allows biofilms to grow at the air-liquid interface. Also, the biofilm-mucosa interaction is more physiological than primary cell cultures, because the communication between different host cells is preserved in the explant model. After the interaction with S. aureus biofilms, explant tissues produced IL-6 and other cytokines polarised to a Th1/Th17 type of immune response. The observed Th1/Th17 immune response differs from previous reports in eosinophilic CRS patients with nasal polyps (CRSwNP) showing a predominant Th2 response. Apparently there is an evolution from early Th1/Th17 immune responses to late Th2 in S. aureus biofilm associated infections. The turning point between these two types of immune responses seems critical in CRS because it could explain the origin of the Th2 inflammation. In the future, the use of long-term animal models could help to illustrate the progression from an initial Th1/Th17 to a late Th2 type of immune response in the sinonasal mucosa. S. aureus biofilms also induced apoptosis in the mucosa as demonstrated by the up-regulation of cleaved caspase-3 in our settings. We also demonstrated the induction and activation of the Nod2 receptor and downstream pathway secondary to S. aureus biofilms. The Nod2 receptor recognises a small portion of peptidoglycan that is available during early phases of S. aureus biofilm formation. The role of Nod2 in CRS and biofilm infections should be evaluated in future studies. In conclusion, we demonstrated that early S. aureus biofilms induce a proinflammatory response in the sinonasal mucosa. This proinflammatory response seems to be crucial for biofilm attachment and persistence, and its modulation could represent an alternative to prevent S. aureus biofilm infections. Secreted staphylococcal products such as alpha ([alpha]) toxin and staphylococcal protein A (SpA) are two virulence factors critical during early biofilm growth. These proteins are also able to generate immune responses and represent targets for potential therapeutic intervention during biofilm infections in the sinonasal mucosa.
Author: Camille Jardeleza Publisher: ISBN: Category : Biofilms Languages : en Pages : 344
Book Description
This thesis aims to address the relationship of Staphylococcus aureus (S. aureus) biofilms to the endogenously produced gas nitric oxide (NO) in chronic rhinosinusitis (CRS). While S. aureus biofilms are associated with recalcitrance and high severity in CRS, the naturally elevated NO gas is significantly lower in sinuses of CRS patients. However, the relationship of these 3 important factors in CRS aetiopathogenesis is poorly defined. To further clarify this host-microbe-environment (NO) relationship, this thesis first looks into the history of each factor, the roles they play in other disease processes, and the most recent clinical findings and applications in current literature. Building on this foundation, the projects emanating from this thesis hoped to fill in some gaps in knowledge of these 3 components, identifying that all are linked to disease manifestation, and that each can mutually contribute to CRS pathogenesis. The first project was designed to establish a clearer description of the relationship between NO and S. aureus biofilms. Utilizing S. aureus strains from CRS patients, these were grown as biofilms and exposed to various NO concentrations mimicking NO levels measured in healthy sinuses vs. CRS patients. We demonstrated the dualistic effects of NO on biofilm growth: increased at lower NO concentrations mimicking diseased sinuses, and anti-biofilm effects at higher concentrations similar to measurements in healthy sinuses. These findings became a stepping stone for the potential design of NO as a therapeutic agent in S. aureus-associated CRS. But first, further characterization of NO's role on the host immune response was needed. The 2nd and 3rd projects aimed to define the host-NO relationship, focusing on the genes involved in NO regulation within the sinonasal mucosa. Because NO is considered one of the reactive oxygen species (ROS), major players of the innate immune response, genes involved in ROS/innate immunity were investigated. CRS patients, with or without polyps, were sub-classified as either with or without S. aureus biofilms, allowing a separate analysis of the role S. aureus biofilms play in the alteration of gene expression. The results showed that S. aureus biofilm presence associates with a significant difference in the certain gene expressions which have specific roles in NO regulation. This indicates that the microorganism may alter or contribute to an impaired localized innate immune response in the sinuses, or alternatively favor growth in genetically susceptible individuals. Although the cause-effect timeline was not established, these results will serve as baseline for future gene and protein studies that will further increase our understanding of the NO-CRS pathophysiology. Lastly, building on the therapeutic potential of NO as an anti-biofilm agent, we aimed to design a suitable NO-based topical agent against S. aureus biofilms. The 4th project tested a multitude of liposome-encapsulated NO formulations in-vitro with the best formulation tested for safety and efficacy in a sheep model of rhinosinusitis. These projects were designed with an aim for future clinical trials, to test a novel NO-based topical agent, which can be used as a safe and efficacious topical sinus rinse to benefit CRS patients.
Author: Almoaidbellah Rammal Publisher: ISBN: Category : Languages : en Pages :
Book Description
"Introduction: Bacteria are suspected to play an important role in the pathogenesis of chronic rhinosinusitis (CRS), yet their exact role remains controversial. We investigated the effect of planktonic and biofilm forms of staphylococcus aureus (SA) and Pseudomonas aeruginosa (PA) on the mucosal innate immune response of CRS patients with chronic gram-positive and gram-negative infection by measuring the level of IL-6 and RANTES, a chemokine with activity on eosinophils and T lymphocytes and by measuring the level of mRNA expression of NOD-1 and NOD-2Method: Ethmoid mucosa of six CRS patients with gram-positive bacteria on culture and five with gram-negative bacteria were compared to ethmoid mucosa of eight control patients. The tissue explants were stimulated with SA and PA extracts in planktonic and biofilm form for six hours, then RANTES and IL-6 levels were measured by ELISA . A quantitative polymerase chain reaction (qPCR) array was used to measure NOD-1 and NOD-2 gene expression. Result: Compared to the control group, CRS patients with gram-negative predominance demonstrated a significantly higher level of RANTES expression in response to all form of bacterial stimuli (P-value
Author: Andrew C. Swift Publisher: Springer Nature ISBN: 3031286901 Category : Medical Languages : en Pages : 646
Book Description
This textbook includes the latest knowledge and advances for a comprehensive range of disorders, including the management of benign and malignant sinonasal tumours. Rhinology is now a fully established and highly popular specialist field that has undergone a major paradigm shift over recent decades. This progressive change has been possible because of the synchronous developments in technology, radiology, therapeutics and pharmacology. These advances have changed clinical practice in every dimension, and this has led to a truly global exponential rise in specialist rhinological interest into the management of sinonasal disorders.Contemporary Rhinology: Science and Practice opens with the basic science of rhinology, with chapters that build an understanding of the nose and sinuses. Chapters cover embryology, anatomy, physiology, immunology, sleep disorders, and more. From there, clinical assessment of the nose and sinuses is discussed. The following sections cover pediatric sinonasal disorders and inflammatory sinus disorders, such as pediatric rhinosinusitis, pediatric nasal deformity, allergic and non-allergic rhinitis, and fungal sinus disease. Following these are several chapters discussing tumors and sinus and skull base surgery. The textbook closes with coverage of a variety of smaller topics, such as epistaxis, trauma to the nose and paranasal sinuses, and nasal obstructions. The textbook features outstanding illustrations, video clips, and key points to enhance understanding and recall.This textbook’s balance of applied science and clinical practicality makes is an ideal resource for anyone from trainee surgeons to established specialists in rhinology.
Author: Marlene L. Durand Publisher: Springer ISBN: 3319748351 Category : Medical Languages : en Pages : 404
Book Description
This text serves as a practical but comprehensive guide to diagnosing and treating ear, nose, throat, and sinus infections. The 30 chapters have been contributed by otolaryngologists and infectious disease specialists who are experts in the field. Topics include common infections such as otitis media, otitis externa, pharyngitis, laryngitis, and acute bacterial sinusitis, as well as less common infections such as mumps, scrofula, malignant otitis externa, Lemierre’s syndrome, invasive fungal sinusitis, and deep neck infections. Human papillomavirus-related neoplasms, biofilms, chronic sinusitis, antibiotic-resistant infections, and measures to prevent surgical site infections are also discussed. Written with the practicing clinician in mind, Infections of the Ears, Nose, Throat, and Sinuses will be an invaluable aid to otolaryngologists, infectious disease specialists, internists, pediatricians, and primary care providers./div
Author: Gunnar Bergenholtz Publisher: John Wiley & Sons ISBN: 1118691385 Category : Medical Languages : en Pages : 651
Book Description
The second edition of Textbook of Endodontology continues the aim of serving the educational needs of dental students and dental practitioners searching for updates on endodontic theories and techniques. Significantly restructured and completely updated, the new edition maintains the ethos of the original, facilitating ease of learning through pedagogical features such as annotated references, core concepts and key literature. It features a number of new chapters on topics ranging from outcomes of endodontic treatment to managing endodontic complications to dental trauma. Additionally, all other chapters have been thoroughly revised and brought up to date to reflect contemporary knowledge and practice. Textbook of Endodontology continues its important function of providing lucid scholarship and clear discussion of biological concepts and treatment principles in endodontics, and as such will be an important update to its current readers and a valuable discovery to its new audience.
Author: Sauro Longhi Publisher: Springer Nature ISBN: 3030338797 Category : Science Languages : en Pages : 212
Book Description
The book describes significant multidisciplinary research findings at the Università Politecnica delle Marche and the expected future advances. It addresses some of the most dramatic challenges posed by today’s fast-growing, global society and the changes it has caused, while also discussing solutions to improve the wellbeing of human beings. The book covers the main research achievements made in the social sciences and humanities, and includes chapters that focus on understanding mechanisms that are relevant to all aspects of economic and social interactions among individuals. In line with Giorgio Fuà’s contribution, the interdisciplinary research being pursued at the Faculty of Economics of Università Politecnica delle Marche is aimed at interpreting the process of economic development in all of its facets, both at the national and local level, with a particular focus on profit and non-profit organizations. Various disciplines are covered, from economics to sociology, history, statistics, mathematics, law, accounting, finance and management.
Author: Christos C. Zouboulis Publisher: Springer ISBN: 3540693750 Category : Medical Languages : en Pages : 729
Book Description
This book, written by experts from across the world, provides comprehensive coverage of acne and rosacea, focusing in particular on pathogenesis and treatment but also considering clinical aspects, prognostic factors, and impacts on quality of life. Both standard knowledge and important, clinically relevant insights that have emerged over the past decade are presented with the goal of assisting the reader in understanding these diseases and improving treatment outcome. It is explained how high-level research has recently given rise to a variety of new concepts in etiology and treatment, and emerging trends are also discussed. The book is in a reader-friendly format that highlights core messages with a very practical and clinical focus. Pathogenesis and Treatment of Acne and Rosacea will be an indispensable reference for all physicians who care for patients with acne or rosacea and for scientists working in the field.
Author: Daniel Anibal Cantero Cajas
Author: Daniel Anibal Cantero Cajas
Author: Camille Jardeleza
Author: Almoaidbellah Rammal
Author: Andrew C. Swift
Author: Marlene L. Durand
Author: 
Author: Gunnar Bergenholtz
Author: 
Author: Sauro Longhi
Author: Christos C. Zouboulis