Osteomyelitis is an infection of bone or bone marrow, usually caused by pyogenic bacteria. It can cultivate by hematogen way or it can cultivate by the help of local soft tissue infection. Osteomyelitis often requires prolonged antibiotic therapy and surgery. But for therapy / antibiotic must reach to effective dose in the bone. So that / for prevention and treatment of osteomyelitis controlled antibiotic release systems can be used. These systems have been developed to deliver antibiotics directly to infected tissue. As a carrier material / polymers are widely use. Polymer can be biodegradable or non biodegradable. The advantage of biodegradable polymers is / you do not need a second surgery for the removal of the carrier material from the body. In this study / vancomycin loaded PLLA/TCP composites were developed and characterized to treat implant related chronic osteomyelitis in experimental rat osteomyelitis model. Some of the composites were prepared by coating the vancomycin loaded composites with PLLA to observe the difference between the coated and uncoated composites. Also, some composites were developed free from the vancomycin to determine the biocompatibility of the composite for the bone tissue. The coating extended the release of the vancomycin up to 5 weeks and changed the surface morphology of the composites. According to the cell culture studies, vancomycin loaded PLLA/TCP composites promoted cell adhesion, cell proliferation and mineralization so / the composite was biocompatible with bone tissue. Radiological and microbiological evaluations showed that vancomycin loaded and coated vancomycin loaded PLLA/TCP composites inhibited MRSA proliferation and treat implant related chronic osteomyelitis.

Introduction: Globally, one in four persons infected with the human immunodeficiency virus (HIV) who are living with the acquired immunodeficiency syndrome (AIDS) will die of tuberculosis (TB). The estimated number of HIV-infected children who die of tuberculosis, especially extrapulmonary TB (EPTB), in Haiti, is only loosely based on facts or investigation. This study proposes to describe demographics of children with EPTB in a pediatric TB hospital in Haiti. The objectives are two-fold. The first objective is to describe the population of children discharged from Grace Children's Hospital with a confirmed diagnosis of tuberculosis overall, and broken down by whether or not the child had an extrapulmonary manifestation of the TB disease. Specifically, we describe the demographic characteristics and the prevalence of HIV and other co-morbidities of the children, in-hospital mortality, and the diagnostic tools used to determine TB infection including the sputum test, and th e documentation of family members also infected. As part of the descriptive process, by examining those with only pulmonary TB (PTB) and EPTB separately, we investigate if they appear to be different sub-populations based on demographic characteristics and clinical measures. The second objective of this work is to determine if there is a positive association between HIV infection and the EPTB manifestation in children with a confirmed diagnosis of TB, both crudely and after adjusting for demographic variables and co-morbidities. Methods: A cross-sectional study design was used to review medical charts of clinically diagnosed pediatric TB cases for a five-year period (January 1, 1999 -- December 31, 2003). This included 492 pulmonary TB and 210 extrapulmonary TB cases. Variables measured included clinical measures and demographic characteristics. Results: Data for 615 hospitalized, clinically diagnosed pediatric TB cases were reviewed. There were 315 (51.4%) males and 298 (48.6%) females with a mean age of 5.40 years (range 0.17 - 14 years), with 214 (37.9%) of the patients aged 0-2 years. Percent males were 47.8% and 57.9% in PTB and EPTB groups respectively (p<0.05). One hundred and seven (17.4%) of patients were HIV positive. Three hundred eighty-eight (63%) of the patients had one or more additional co-morbidities: [anemia 299 (48.6%), intestinal parasites 93 (15.1%), malaria 58 (9.4%) and gastroenteritis 19 (3.1%)]. Nearly 85% of the children were undernourished. Eighty-three child patients (13.5%) died in the hospital. Children with EPTB were much more likely to be over the age of two (74% vs. 56% in PTB group), resulting in a highly significant Chi-square stati stic. The overall difference in mean age, however, was only borderline significant with children with EPTB being slightly older [p=0.059] and age was only weakly associated with TB group. They were much less likely to be HIV positive (8.6% vs. 22%, p<0.01). Children in the EPTB group were somewhat less likely to die in the hospital (10.0% vs. 15.4%, p=0.066). The OR was greater than 4 for HIV and was greater than 2 for poor nutrition status [p<0.01 for each]. Conclusion: There was no association in this model between EPTB and mortality. The apparent univariate association between EPTB and reduced mortality can be explained by lower prevalence of HIV and poor nutrition status in this sub-sample. This study has implications for hospital-based pediatric TB diagnosis and epidemiology in resource-poor countries.

As fraturas de mandíbula são freqüentes e o seu tratamento é por meio de fixação interna rígida. Complicações podem ocorrer após o tratamento das fraturas mandibulares levando a necessidade de reabordagem cirúrgica, havendo poucos estudos a esse respeito na literatura. A proposta deste estudo retrospectivo foi avaliar as características, os possíveis fatores de risco e os tipos de tratamento realizado em pacientes que necessitaram de reabordagem cirúrgica de fraturas de mandíbula tratadas com fixação interna rígida (FIR). Dentre 364 pacientes tratados por fraturas de mandíbula com FIR, houve 17 pacientes (4,7%) que necessitaram de reabordagem cirúrgica, tendo sido incluídos três pacientes provenientes de outros serviços, totalizando 20 casos com necessidade de nova cirurgia. Houve predomínio do gênero masculino, com idade média de 31,4 anos, sendo freqüentes o tabagismo e o etilismo. Foram freqüentes fraturas múltiplas e cominutivas nas regiões de corpo e ângulo mandibular, dente no traço e exposição intraoral da fratura. O tempo de espera para primeira cirurgia foi alto e o acesso extraoral e o sistema de fixação menos rígido 2.0 mm foram freqüentes. As complicações mais comuns foram dor, infecção e mobilidade anormal. Nas culturas bacterianas houve predomínio do Staphylococcus aureus e a imagem mais freqüente foi de reabsorção óssea difusa, seguida por parafuso solto, seqüestro ósseo, traço de fratura visível, fixação solta e placa fraturada. A reabordagem cirúrgica ocorreu em média de 7,5 meses após a primeira cirurgia e constou de remoção dos meios de fixação associada ou não a nova fixação ou ainda a remoção de seqüestro ósseo, sendo que apenas um caso necessitou de refratura. Histologicamente houve predomínio de osteomielite crônica. Os diagnósticos em ordem decrescente foram infecção, pseudoartrose, osteomielite e placa exposta, sendo que muitos pacientes tiveram mais de um diagnóstico. Foi destacada a freqüência de tabagismo e etilismo, fraturas múltiplas e cominutivas na região de corpo e ângulo mandibular, dente no traço, exposição intraoral, tempo de espera alto e acesso extraoral predispondo complicações das fraturas mandibulares e exames de imagem de reabsorção óssea, fixação e parafusos solto e seqüestro ósseo e diagnóstico histológico de osteomielite como característica dos casos requerendo nova cirurgia. / Mandibular fractures are frequent and their treatment is through rigid internal fixation (RIF). Complications can occur after treatment of the mandibular fractures which may require a new surgical procedure, and there are a few studies about that in the literature. The purpose of this retrospective study was to evaluate the characteristics, possible risk factors, and the kinds of treatment did in patients which needed another surgery after treatment of mandibular fracture with RIF. From 364 patients with mandibular fractures treated by RIF, there were 17 patients (4.7%) with need of a new surgery, and 3 patients coming from another city were included, comprising a total of 20 patients who needed a new surgery. There was predominance of the male gender, with a mean age of 31.4 years, being frequent smoking and alcohol abuse. Multiple and comminuted fractures on the body and angle sites, teeth in the fracture line, and intraorally exposed fractures were frequent. Delay time to the first surgery was high, and extraoral approaches and system 2.0mm were predominant. The most common complications were pain, infection and abnormal mobility. In the bacterial culture there was predominance of Staphylococcus aureus, and the most frequent radiographic images were of diffuse bone resorption, loosening of screws, bone sequestration, fracture line visible, loose fixation, and fractured plate. A new surgery occurred with a mean of 7.5 months after the first intervention and comprised plate and screws removal associated or not to a new fixation or bone sequestra removal, and only a case the fracture needed to be osteotomized. Histologically there was predominance of chronic osteomyelitis. The diagnoses in decreasing order were infection, nonunion, osteomyelitis and exposed plate, although many patients had more than one diagnosis. It was evidenced the frequency of smoking and alcohol abuse, multiple and comminuted fracture on the body and angle regions, teeth in the fracture line, intraoral fracture exposition, high delay time and extraoral approaches predisposing complications of the mandibular fractures, and images showing bony resorption, loose hardware and bone sequestra, as well as histological diagnosis of osteomyelitis as characteristic of the cases requiring a new surgery.

In the first part of these studies, we have performed standard microsurgical procedures provide a solution for long standing bone and soft tissue defects, even in cases of longstanding osteomyelitis of long bones. When long bony segments are missing, the microvascular bone transfer provides a reliable method. In smaller soft tissue and bone defects, the application of a descending genicular osteomyocutaneous flap provides an option with low donor site morbidity. In the second part, we have focussed on reducing the donor site morbidity and expanded on the application of tissue engineering methods. MSCs derived from bone marrow can be injected percutaneous or be combined with an autologous bony scaffold for treatment of delayed union and nonunion. The outcome of our studies, however, limited in number of patients, clearly showed the possibilities and advantages of this new approach. A multimodality approach is essential, but it can provide promising solutions. Well-established microvascular and modern biotechnology methods will improve patient satisfaction and functional recovery in severe limb trauma, often the result of high-energy motorcycle accidents. / Doctorat en Sciences médicales (Médecine) / info:eu-repo/semantics/nonPublished

Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal.

S. aureus est un pathogène humain qui produit une grande variété de facteurs de virulence, dont la leucocidine de Panton Valentine. Cette toxine est à l’origine de symptomatologies potentiellement sévères telles que la pneumonie nécrosante et l’ostéomyélite compliquée récidivante. Malgré la faible prévalence des gènes de la PVL au sein de souches de S. aureus, nous assistons à une émergence et à une diffusion de souches S. aureus résistantes à la méticilline d’origine communautaire (SARM-C) produisant la PVL. Bien que hautement conservée au sein de différents génomes, la PVL produite par les souches SARM-C américaines USA300 porte une substitution His176Arg avec un impact potentiel sur la fonctionnalité de la PVL. Nous avons étudié la distribution de ce polymorphisme au sein d’une sélection de souches SARM-C isolées de divers continents et nous avons confirmé le rôle leucotoxique de la PVL envers les neutrophiles humains quel que soit le fond génétique de la souche d’origine. Nous avons mis au point un modèle expérimental de lapin afin d’étudier le rôle de la PVL secrétée par la souche USA300 dans la pathogenèse de l’ostéomyélite. La PVL s’est révélée être un déterminant de la gravité de la maladie en termes de persistance et extension de l’infection, ainsi que d’amplitude de la réaction inflammatoire. Dès lors que nous avons conforté le rôle pathogène de la PVL, nous avons exploré l’effet des antibiotiques sur l’expression de la leucocidine. Nous avons observé après traitement avec l’oxacilline et l’imipénème une augmentation de la production de PVL. Cette augmentation est le résultat d’une activation transcriptionnelle des gènes de la PVL, activation médiée par les protéines liant la pénicilline et des régulateurs de la virulence staphylococcique, sarA et rot. D’autres antibiotiques la clindamycine, le linézolide et la rifampicine exercent un effet inhibiteur sur la production de PVL et bloquent l’induction de toxine par les bêta-lactamines. Sur la base de ces observations, nous recommandons pour le traitement des infections sévères à S. aureus producteur de PVL l’utilisation de l’oxacilline en association avec la clindamycine ou la rifampicine pour S. aureus sensible à la méticilline et du linézolide pour le SARM. / S. aureus is a human pathogen producing a large variety of virulence factors such as the Panton Valentine leukocidin (PVL). This toxin has been epidemiologically related to severe diseases such as necrotising pneumonia and recurrent osteomyelitis. The world wide spreading of PVL producing community acquired methicillin resistant S. aureus (CA-MRSA) has been reported. Although highly preserved within various genomes, the sequence of PVL produced by the american CA-MRSA strain USA300 carries a His176Arg substitution with a potential impact on the functionality of the leukocidin. We studied the distribution of this polymorphism within a selection of CA-MRSA strains isolated from various continents and we confirmed PVL toxicity towards human neutrophiles regardless to the genetic background of the harboring strain. We used an experimental rabbit model in order to study the relevancy of USA300 secreted PVL in the pathogenesis of osteomyelitis. We showed that PVL is a determinant of disease severity in terms of persistence and extension of the infection, as well as amplitude of the inflammatory reaction. We investigated the effect of antibiotics on the expression of the leukocidin. We observed increase PVL production after oxacilline and imipenem treatment. This was the consequence of trascriptional activation of PVL genes, mediated by penicillin binding proteins and S. aureus virulence regulators sarA and rot. Other antibiotics such as clindamycin, linezolid and rifampicin decreased PVL production and suppressed the inductor effect of beta-lactams. Based on these observations, we recommend for the treatment of the severe PVL induced diseases the use of oxacillin associated with either clindamycin or rifampicin for methicillin susceptible S. aureus or linezolid for MRSA.

INTRODUÇÃO: As infecções osteoarticulares permanecem como um grande desafio para os profissionais de saúde envolvidos no seu manejo, a despeito do sucesso obtido com a introdução dos antimicrobianos para o tratamento das doenças infectocontagiosas no final da década de 1930. O Staphylococcus aureus (S. aureus) é o agente mais frequentemente encontrado nestas infecções e também é o agente mais estudado, porém possuímos poucas informações disponíveis na literatura médica a respeito das osteomielites por bacilos Gram-negativos (BGN). OBJETIVOS: A caracterização clínica e microbiológica dos episódios de osteomielite causadas por bacilos Gram-negativos. A determinação das diferenças evolutivas e dos fatores de risco para a ocorrência de osteomielite por bacilos Gram-negativos, quando comparadas à osteomielite causada por S. aureus. MÉTODOS: Análise retrospectiva dos casos de osteomielite causadas por bacilos Gram-negativos atendidos no Instituto de Ortopedia e Traumatologia do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo no período de janeiro de 2007 a janeiro de 2009. Apenas amostras de osso ou aspirado de canal medular foram consideradas válidas. RESULTADOS: Foram incluídos 89 pacientes no grupo S. aureus e 101 pacientes no grupo BGN. Os pacientes do grupo BGN eram predominantemente do sexo masculino (63%), com mediana de 42 anos de idade. Apresentaram-se com osteomielite crônica (43%) e osteomielite aguda associada à fratura exposta (32%), nos membros inferiores (71%), cuja principal sintomatologia inicial foi a fistulização (69%). Quando comparado ao grupo S. aureus, o grupo BGN estava estatisticamente associado com o antecedente de fratura exposta (35% vs. 18%; p=0,0064), apresentando ainda um maior tempo de internação hospitalar (mediana 41 vs. 24 dias; p=0,0114), maior tempo para a obtenção da primeira cultura positiva (mediana 10 vs. 6,5 dias; p=0,0042), antibioticoterapia mais prolongada (mediana 40 vs. 24 dias; p=0,0329), maior número de procedimentos cirúrgicos (média 3,41 vs. 2,47; p=0,0173) e maior uso de reparo do revestimento cutâneo (31% vs. 9%; p=0,0005). O grupo S. aureus estava estatisticamente associado com as osteomielites da coluna vertebral (23,6% vs. 6,9%; p=0,0008). Foram isolados 121 agentes Gram-negativos de 101 amostras clínicas e os agentes mais frequentes foram Enterobacter spp. (24,7%), Acinetobacter baumannii (21,4%), Pseudomonas aeruginosa (19,8%) e Klebsiella pneumoniae (8,2%). CONCLUSÕES: Os 101 pacientes portadores de osteomielite por BGN eram na sua maioria jovens, do sexo masculino, vítimas de traumas nos membros inferiores e que desenvolveram osteomielite aguda e crônica associadas a fraturas expostas. Os pacientes do grupo BGN necessitaram de um número maior de procedimentos cirúrgicos, maior uso de reparo do revestimento cutâneo, permaneceram internados por mais tempo, necessitaram de um número de dias maior para o isolamento do agente infeccioso e utilizaram antibioticoterapia mais prolongada, quando comparados aos pacientes do grupo S. aureus. O antecedente de fratura exposta foi o principal fator de risco para o desenvolvimento de osteomielite por um BGN, quando comparado ao grupo S. aureus / INTRODUCTION: Bone and joint infection remains a serious therapeutic challenge, despite the high success rate observed with antibiotic therapy in most bacterial disease since the end of 1930 decade. Staphylococcus aureus (S. aureus) is the most studied and the most frequently isolated pathogen, but there is insufficient information in medical literature regarding Gram- negative bacilli (GNB) osteomyelitis. OBJECTIVES: Describe clinical and microbiological characteristics of Gram-negative bacilli osteomyelitis. Establish evolving differences and risk factors for the occurrence of GNB osteomyelitis, compared to S. aureus osteomyelitis. METHODS: Retrospective analysis of all patients with GNB osteomyelitis treated at Institute of Orthopedics and Traumatology, Hospital das Clínicas - School of Medicine, Universidade de São Paulo from january 2007 to january 2009. Only bone or bone marrow aspirate samples were included. RESULTS: 89 patients were included in S. aureus group and 101 patients were included in GNB group. Patients in GNB group were mostly male (63%), with median age of 42 years. At presentation, they had chronic osteomyelitis (43%) and acute open-fracture associated osteomyelitis (32%), in the lower limbs (71%), with a discharging sinus as the main clinical sign (69%). When compared to S. aureus group, GNB group was statistically associated with a previous history of open-fracture (35% vs. 18%; p=0.0064), showed a longer length of hospital stay (median 41 vs. 24 days; p=0.0114), a higher number of days to isolate the infective bacteria (median 10 vs. 6,5 days; p=0.0042), a longer use of antibiotics (median 40 vs. 24 days; p=0.0329), a higher number of surgical procedures (mean 3,41 vs. 2,47; p=0.0173) and a higher rate of soft- tissue reconstruction (31% vs. 9%; p=0.0005). S. aureus group was statistically associated with spine osteomyelitis (23,6% vs. 6.9%; p=0.0008). 121 Gram-negative pathogens were isolated from 101 clinical samples and the most frequent agents were Enterobacter spp. (24.7%), Acinetobacter baumannii (21.4%), Pseudomonas aeruginosa (19.8%) and Klebsiella pneumoniae (8.2%). CONCLUSIONS: Patients with GNB osteomyelitis were mainly young, male, with lower limb trauma and developed chronic and open- fracture associated osteomyelitis. Patients in GNB group had a higher number of surgical procedures, a higher rate of soft-tissue reconstruction, a longer length of hospitalization, a longer time to isolate the infective bacteria and a prolonged use of antibiotics, when compared to patients in S. aureus group. A previous history of open-fracture was the main risk factor to development of GNB osteomyelitis, compared to S. aureus group

Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal

INTRODUÇÃO: As infecções osteoarticulares permanecem como um grande desafio para os profissionais de saúde envolvidos no seu manejo, a despeito do sucesso obtido com a introdução dos antimicrobianos para o tratamento das doenças infectocontagiosas no final da década de 1930. O Staphylococcus aureus (S. aureus) é o agente mais frequentemente encontrado nestas infecções e também é o agente mais estudado, porém possuímos poucas informações disponíveis na literatura médica a respeito das osteomielites por bacilos Gram-negativos (BGN). OBJETIVOS: A caracterização clínica e microbiológica dos episódios de osteomielite causadas por bacilos Gram-negativos. A determinação das diferenças evolutivas e dos fatores de risco para a ocorrência de osteomielite por bacilos Gram-negativos, quando comparadas à osteomielite causada por S. aureus. MÉTODOS: Análise retrospectiva dos casos de osteomielite causadas por bacilos Gram-negativos atendidos no Instituto de Ortopedia e Traumatologia do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo no período de janeiro de 2007 a janeiro de 2009. Apenas amostras de osso ou aspirado de canal medular foram consideradas válidas. RESULTADOS: Foram incluídos 89 pacientes no grupo S. aureus e 101 pacientes no grupo BGN. Os pacientes do grupo BGN eram predominantemente do sexo masculino (63%), com mediana de 42 anos de idade. Apresentaram-se com osteomielite crônica (43%) e osteomielite aguda associada à fratura exposta (32%), nos membros inferiores (71%), cuja principal sintomatologia inicial foi a fistulização (69%). Quando comparado ao grupo S. aureus, o grupo BGN estava estatisticamente associado com o antecedente de fratura exposta (35% vs. 18%; p=0,0064), apresentando ainda um maior tempo de internação hospitalar (mediana 41 vs. 24 dias; p=0,0114), maior tempo para a obtenção da primeira cultura positiva (mediana 10 vs. 6,5 dias; p=0,0042), antibioticoterapia mais prolongada (mediana 40 vs. 24 dias; p=0,0329), maior número de procedimentos cirúrgicos (média 3,41 vs. 2,47; p=0,0173) e maior uso de reparo do revestimento cutâneo (31% vs. 9%; p=0,0005). O grupo S. aureus estava estatisticamente associado com as osteomielites da coluna vertebral (23,6% vs. 6,9%; p=0,0008). Foram isolados 121 agentes Gram-negativos de 101 amostras clínicas e os agentes mais frequentes foram Enterobacter spp. (24,7%), Acinetobacter baumannii (21,4%), Pseudomonas aeruginosa (19,8%) e Klebsiella pneumoniae (8,2%). CONCLUSÕES: Os 101 pacientes portadores de osteomielite por BGN eram na sua maioria jovens, do sexo masculino, vítimas de traumas nos membros inferiores e que desenvolveram osteomielite aguda e crônica associadas a fraturas expostas. Os pacientes do grupo BGN necessitaram de um número maior de procedimentos cirúrgicos, maior uso de reparo do revestimento cutâneo, permaneceram internados por mais tempo, necessitaram de um número de dias maior para o isolamento do agente infeccioso e utilizaram antibioticoterapia mais prolongada, quando comparados aos pacientes do grupo S. aureus. O antecedente de fratura exposta foi o principal fator de risco para o desenvolvimento de osteomielite por um BGN, quando comparado ao grupo S. aureus / INTRODUCTION: Bone and joint infection remains a serious therapeutic challenge, despite the high success rate observed with antibiotic therapy in most bacterial disease since the end of 1930 decade. Staphylococcus aureus (S. aureus) is the most studied and the most frequently isolated pathogen, but there is insufficient information in medical literature regarding Gram- negative bacilli (GNB) osteomyelitis. OBJECTIVES: Describe clinical and microbiological characteristics of Gram-negative bacilli osteomyelitis. Establish evolving differences and risk factors for the occurrence of GNB osteomyelitis, compared to S. aureus osteomyelitis. METHODS: Retrospective analysis of all patients with GNB osteomyelitis treated at Institute of Orthopedics and Traumatology, Hospital das Clínicas - School of Medicine, Universidade de São Paulo from january 2007 to january 2009. Only bone or bone marrow aspirate samples were included. RESULTS: 89 patients were included in S. aureus group and 101 patients were included in GNB group. Patients in GNB group were mostly male (63%), with median age of 42 years. At presentation, they had chronic osteomyelitis (43%) and acute open-fracture associated osteomyelitis (32%), in the lower limbs (71%), with a discharging sinus as the main clinical sign (69%). When compared to S. aureus group, GNB group was statistically associated with a previous history of open-fracture (35% vs. 18%; p=0.0064), showed a longer length of hospital stay (median 41 vs. 24 days; p=0.0114), a higher number of days to isolate the infective bacteria (median 10 vs. 6,5 days; p=0.0042), a longer use of antibiotics (median 40 vs. 24 days; p=0.0329), a higher number of surgical procedures (mean 3,41 vs. 2,47; p=0.0173) and a higher rate of soft- tissue reconstruction (31% vs. 9%; p=0.0005). S. aureus group was statistically associated with spine osteomyelitis (23,6% vs. 6.9%; p=0.0008). 121 Gram-negative pathogens were isolated from 101 clinical samples and the most frequent agents were Enterobacter spp. (24.7%), Acinetobacter baumannii (21.4%), Pseudomonas aeruginosa (19.8%) and Klebsiella pneumoniae (8.2%). CONCLUSIONS: Patients with GNB osteomyelitis were mainly young, male, with lower limb trauma and developed chronic and open- fracture associated osteomyelitis. Patients in GNB group had a higher number of surgical procedures, a higher rate of soft-tissue reconstruction, a longer length of hospitalization, a longer time to isolate the infective bacteria and a prolonged use of antibiotics, when compared to patients in S. aureus group. A previous history of open-fracture was the main risk factor to development of GNB osteomyelitis, compared to S. aureus group

The development of autoinflammatory diseases is caused by the dysregulation of innate immune mechanisms. This leads to the development of spontaneous inflammation. Mice lacking adaptor protein PSTPIP2 develop chronic autoinflammatory osteomyelitis due to higher activity of neutrophil granulocytes and their increased production of IL-1β. .β. PSTPIP2 interacts with PEST phosphatases and kinase CSK. These proteins are impor- tant negative regulators of Src family kinases. In this diploma thesis, the role of Src family kinases and the role of their positive regulator phosphatase CD45 in the development of chronic autoinflammatory osteomyelitis was studied. For this purpose, a mouse model of chronic autoinflammatory osteomyelitis (CMO) lacking CD45 was used. These mice deve- lop the disease with delayed kinetics. Bone marrow cells isolated from these mice produce less IL-1β. upon silica activation and have lower phosphorylation of ERK MAP kinase. It isβ. probably caused by higher phosphorylation of the inhibitory tyrosine of Src family kinases resulting in their lower activity. The presence of different immune cell populations in the bone marrow, spleen and blood of these mice was also monitored in these mice. The re- sults of this work contribute to a better understanding of the role of Src family...