Acute otitis media is the most common illness diagnosed during early childhood that can cause significant morbidity (Brook, 1994) and sometimes can cause irreversible sequelae such as a hearing defect and subsequent learning difficulties (Klein, 1994). The aims of the research presented here were to study some aspects of the middle ear defence mechanisms in both immune and non-immune rats following experimental otitis media (OM) with two pathogens nontypeable Haemophilus influenzae (NTHi) and Moraxella catarrhalis (M. catarrhalis). This study also aimed at developing a suitable technique for preparing immunohistochemical staining of middle ear sections (chapter 2). A previous study has shown that a regime where rats received an IPP immunisation combined with an IT boost was effective in enhancing clearance of a middle ear infection with the same strain of NTHi and also in the presence of a concomitant viral infection (Moore et al, 2001). Results of this study have shown that for NTHi infection a distinct cellular influx to the middle ear in the immune rats was accompanied by an enhanced bacterial clearance compared to the non-immunised rats (chapter 3). This cellular influx was responsible for the remarkable reduction in the bacterial number. The sharp decline in PMNs numbers in the NTHi immunised rats that followed complete bacterial clearance at 72h post infection (Table 3.1) indicate a more effectively controlled down regulation of this cell infiltrate than the non-immunised rats. For M. catarrhalis infection, there was no difference in cell infiltrate between immune and non-immune rats, but enhanced clearance of the bacteria were observed for the immune animals. The histopathological changes in the middle ear mucosa of rats with experimentally induced infection were studied to provide a better understanding about the distribution of the inflammatory cells and changes in the mucosa during the first 24h post challenge with NTHi and M. catarrhalis (Chapter 4). These changes have not been previously studied for the two pathogens at 24h post challenge in rats. Induced infections with the two pathogens were found to produce similar histopathological changes but more inflammatory infiltration was observed within the infected mucosa with NTHi than that seen with M. catarrhalis. The infections were characterized by increased thickness of the middle ear mucosa, Eustachian tube mucosa, periosteum and tympanic membrane. There was also an increase in the number and size of small blood vessels at all sites, and these small blood vessels seem to be the source of the inflammatory infiltration into the middle ear mucosa and middle ear cavity during the infection. These findings provided an essential background to the immunohistochemical study. The effect of mucosal immunisation on the distribution of CD4+T cells and CD8+T cells has not been investigated previously. Results of the present study (Chapter 5) show the pattern of distribution of these cells during the first 48h post infection with NTHi in the rat. The number of CD4+and CD8+T cells peaked at 24h post infection in the nonimmunised animal and were highest at 48h post-infection in the immunised rats. The difference in response in the immunised rats may represent regulation of the inflammatory response by the immune system. The inflammatory response regulation is indicated by the difference in cellular influx into the immune rats and the response in the immune rats that corresponds to enhanced bacterial clearance prior to a decrease in numbers of inflammatory cells once the bacteria was no longer detected (Chapter 3). This resolution of the inflammatory mass would reduce the opportunity for continued damage to local tissue. These changes are also supported by the reduction in the thickness of the middle ear mucosa of the immunised rats especially at 24h and 48h post-infection (Chapter 5). This study has shown that there are distinct differences in the rate of bacterial clearance and cellular changes in the middle ear mucosa and tympanic bulla in immunised rats during a middle ear infection. Future studies are still required to gain a better understanding of differences in the inflammatory response for both pathogens, NTHi and M. catarrhalis.

Thesis (M.A.)--Northern Kentucky University, 2008. / Made available through ProQuest. Publication number: AAT 1450592. ProQuest document ID: 1495953201. Includes bibliographical references (p. 30-32)

Thesis (doctoral)--Lund University, 1997. / Added t.p. with thesis statement inserted.

Thesis (doctoral)--Lund University, 1997. / Added t.p. with thesis statement inserted.

Este estudo teve como objetivo verificar a liberação de xilitol em saliva artificial ao longo do tempo após aplicação de verniz contendo 10% e 20% do açúcar. Para tal, 15 blocos de dentes bovinos foram divididos em três grupos (Grupo 1- recebeu verniz a 10%; Grupo 2 - recebeu verniz a 20% e Grupo 3 - recebeu verniz sem xilitol). Na seqüência, cada bloco foi imerso em tubo de microcentrífuga contendo 500 µL de saliva artificial. Foram coletadas e analisadas as amostras salivares em diferentes tempos após a aplicação do verniz (1h, 8h, 12h, 16h, 24h, 48h e 72h). Comparando-se os valores de concentração de xilitol em mg/L nos grupos G1 e G2, pode-se observar que houve diferença estatisticamente significante entre os grupos (ANOVA, F=32,68, p=0,0004) e tempos (ANOVA, F=2465,53, p=0,0000). Foi observada interação entre as variáveis grupo e tempo (ANOVA, F=1486,25, p=0,0000). Notou-se uma liberação significativamente maior no Grupo G2 nos tempos de 1 h (168,96 mg/L) e 8 h (164,22 mg/L), quando comparados com o Grupo G1 (1 h=63,42 mg/L e 8 h=69,52 mg/L), conforme detectado pelo teste de Tukey (p=0,0002). No entanto, nos tempos de 12 h, 16 h, 24 h, 48 h e 72 h, a liberação do açúcar foi significativamente maior no Grupo 1 (56,92 mg/L; 49,70 mg/L; 49,40 mg/L; 55,52 mg/L; 32,66 mg/L, respectivamente) em relação ao Grupo 2 (29,90 mg/L; 18,52 mg/L; 19,76 mg/L; 24,20 mg/L; 12,72 mg/L, respectivamente), conforme detectado pelo teste de Tukey (p=0,0002). Portanto, o verniz contendo 10% de xilitol liberou maiores concentrações do açúcar em períodos de tempo mais longos, denotando-se em uma liberação mais lenta e homogênea deste verniz. / The aim of this study was to test xylitol release in artificial saliva along time after application of varnishes containing 10% and 20% xylitol. For this purpose, 15 block of bovine teeth were divided into three groups (Group 1-varnish 10%; Group 2-varnish 20%; Group 3-control). In sequence, each block was immersed in a microcentrifuge tube containing 500 µL of artificial saliva. Saliva samples were collected and analyzed for xylitol in different times after varnishes application (1h, 8h, 12h, 16h, 24h, 48h e 72h). Data were analyzed by 2-way ANOVA and Tukey?s test (p<0.05). An interaction between group and time was observed (ANOVA, F=1,486.25, p=0.0000). Xylitol release was significantly higher for Group G2 in times 1 h (168.96 mg/l) and 8 h (164.22 mg/l) when compared with Group G1 (1h=63.42 mg/l e 8h=69.52 mg/l). However, for the other periods, the sugar release was significantly higher in Group 1(56.92 mg/l; 49.70 mg/l; 49.40 mg/l; 55.52mg/l and 32.66 mg/l, respectively, for 12 h, 16 h, 24 h, 48 h and 72 h) when compared to Group G2 (29.90 mg/l; 18.52 mg/l; 19.76 mg/l; 24.20 mg/l and 12.72 mg/l, respectively). In conclusion, the varnish containing 10% xylitol released sugar more slowly and for longer periods, characterizing a more homogeneous release.

Thesis (M.Sc. Biological Sciences)--University of Waikato, 2007. / Title from PDF cover (viewed February 27, 2008) Includes bibliographical references (p. 189-199)

Este estudo teve como objetivo verificar a liberação de xilitol em saliva artificial ao longo do tempo após aplicação de verniz contendo 10% e 20% do açúcar. Para tal, 15 blocos de dentes bovinos foram divididos em três grupos (Grupo 1- recebeu verniz a 10%; Grupo 2 - recebeu verniz a 20% e Grupo 3 - recebeu verniz sem xilitol). Na seqüência, cada bloco foi imerso em tubo de microcentrífuga contendo 500 µL de saliva artificial. Foram coletadas e analisadas as amostras salivares em diferentes tempos após a aplicação do verniz (1h, 8h, 12h, 16h, 24h, 48h e 72h). Comparando-se os valores de concentração de xilitol em mg/L nos grupos G1 e G2, pode-se observar que houve diferença estatisticamente significante entre os grupos (ANOVA, F=32,68, p=0,0004) e tempos (ANOVA, F=2465,53, p=0,0000). Foi observada interação entre as variáveis grupo e tempo (ANOVA, F=1486,25, p=0,0000). Notou-se uma liberação significativamente maior no Grupo G2 nos tempos de 1 h (168,96 mg/L) e 8 h (164,22 mg/L), quando comparados com o Grupo G1 (1 h=63,42 mg/L e 8 h=69,52 mg/L), conforme detectado pelo teste de Tukey (p=0,0002). No entanto, nos tempos de 12 h, 16 h, 24 h, 48 h e 72 h, a liberação do açúcar foi significativamente maior no Grupo 1 (56,92 mg/L; 49,70 mg/L; 49,40 mg/L; 55,52 mg/L; 32,66 mg/L, respectivamente) em relação ao Grupo 2 (29,90 mg/L; 18,52 mg/L; 19,76 mg/L; 24,20 mg/L; 12,72 mg/L, respectivamente), conforme detectado pelo teste de Tukey (p=0,0002). Portanto, o verniz contendo 10% de xilitol liberou maiores concentrações do açúcar em períodos de tempo mais longos, denotando-se em uma liberação mais lenta e homogênea deste verniz. / The aim of this study was to test xylitol release in artificial saliva along time after application of varnishes containing 10% and 20% xylitol. For this purpose, 15 block of bovine teeth were divided into three groups (Group 1-varnish 10%; Group 2-varnish 20%; Group 3-control). In sequence, each block was immersed in a microcentrifuge tube containing 500 µL of artificial saliva. Saliva samples were collected and analyzed for xylitol in different times after varnishes application (1h, 8h, 12h, 16h, 24h, 48h e 72h). Data were analyzed by 2-way ANOVA and Tukey?s test (p<0.05). An interaction between group and time was observed (ANOVA, F=1,486.25, p=0.0000). Xylitol release was significantly higher for Group G2 in times 1 h (168.96 mg/l) and 8 h (164.22 mg/l) when compared with Group G1 (1h=63.42 mg/l e 8h=69.52 mg/l). However, for the other periods, the sugar release was significantly higher in Group 1(56.92 mg/l; 49.70 mg/l; 49.40 mg/l; 55.52mg/l and 32.66 mg/l, respectively, for 12 h, 16 h, 24 h, 48 h and 72 h) when compared to Group G2 (29.90 mg/l; 18.52 mg/l; 19.76 mg/l; 24.20 mg/l and 12.72 mg/l, respectively). In conclusion, the varnish containing 10% xylitol released sugar more slowly and for longer periods, characterizing a more homogeneous release.

<p>Acute otitis media (AOM) is a common disease in childhood and is one of the most common causes for outpatient antibiotic treatment. The major aetiological agents of AOM have varied over the decades. Now the three most common pathogens are <i>Streptococcus pneumoniae</i>, <i>Haemophilus influenzae</i> and <i>Moraxella catarrhalis</i>. The resistance patterns of these organisms have also varied from the beginning of the antibiotic era to the situation we have today with an increasing incidence of penicillin-resistant <i>S. pneumoniae</i> and a moderate to high frequency of beta-lactamase production in <i>H. influenzae</i> and <i>M. catarrhalis</i>. In Sweden we have continued to use the Scandinavian treatment policy of penicillins as the first-line antibiotic treatment of AOM, which has been implemented with good results in the past. The question is if this policy will continue to have acceptable treatment results.</p><p>In order to investigate aspects of treatment, protection and structural changes in AOM, an animal model was used.</p><p>Amoxicillin treatment of AOM caused by <i>H. influenzae</i> was studied. Amoxicillin treatment was shown to shorten the duration of the infection and to reduce the morphological changes normally observed after an untreated AOM. The influence of antibiotic treatment on recurrent AOM was evaluated. Amoxicillin treatment did not lead to less protection against reinfection. Abstaining from antibiotics did not improve the levels of serum IgG antibodies. The IgG levels were significantly higher in treated animals after rechallenge. AOM caused by <i>H</i>. <i>influenzae</i> with a non-beta-lactamase-mediated resistance to beta-lactams was investigated and it was observed that during amoxicillin treatment the chromosomal changes mediating resistance were possibly advantageous for the bacterium. In cultures from children with AOM, there is sometimes growth of several bacteria. The possibility of a sheltering effect of beta-lactamase-producing <i>H. influenzae</i> on a penicillin-sensitive <i>S. pneumoniae</i> in a mixed infection was investigated, and amoxicillin was shown to eradicate the pneumococci from the middle ear despite the presence of beta-lactamase. An increasingly cultured bacterium in nasopharynx and in AOM is <i>M. catarrhalis</i>. It is now beta-lactamase-producing in almost 100% of cases and is thus not eradicated by penicillins. An animal model of AOM caused by beta-lactamase-producing <i>M. catarrhalis</i> was established to study the course of this infection with the possibility of evaluating aspects of virulence between AOM pathogens. The AOM observed was a self-limiting disease.</p><p>The results obtained in this study in a rat model support the continuing use of penicillins as first-line drugs in the treatment of AOM. Penicillins are not sufficient to treat all causative agents, but the majority of pathogens including the most virulent bacteria are eradicated from the middle ear. </p>

Acute otitis media (AOM) is a common disease in childhood and is one of the most common causes for outpatient antibiotic treatment. The major aetiological agents of AOM have varied over the decades. Now the three most common pathogens are Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis. The resistance patterns of these organisms have also varied from the beginning of the antibiotic era to the situation we have today with an increasing incidence of penicillin-resistant S. pneumoniae and a moderate to high frequency of beta-lactamase production in H. influenzae and M. catarrhalis. In Sweden we have continued to use the Scandinavian treatment policy of penicillins as the first-line antibiotic treatment of AOM, which has been implemented with good results in the past. The question is if this policy will continue to have acceptable treatment results. In order to investigate aspects of treatment, protection and structural changes in AOM, an animal model was used. Amoxicillin treatment of AOM caused by H. influenzae was studied. Amoxicillin treatment was shown to shorten the duration of the infection and to reduce the morphological changes normally observed after an untreated AOM. The influence of antibiotic treatment on recurrent AOM was evaluated. Amoxicillin treatment did not lead to less protection against reinfection. Abstaining from antibiotics did not improve the levels of serum IgG antibodies. The IgG levels were significantly higher in treated animals after rechallenge. AOM caused by H. influenzae with a non-beta-lactamase-mediated resistance to beta-lactams was investigated and it was observed that during amoxicillin treatment the chromosomal changes mediating resistance were possibly advantageous for the bacterium. In cultures from children with AOM, there is sometimes growth of several bacteria. The possibility of a sheltering effect of beta-lactamase-producing H. influenzae on a penicillin-sensitive S. pneumoniae in a mixed infection was investigated, and amoxicillin was shown to eradicate the pneumococci from the middle ear despite the presence of beta-lactamase. An increasingly cultured bacterium in nasopharynx and in AOM is M. catarrhalis. It is now beta-lactamase-producing in almost 100% of cases and is thus not eradicated by penicillins. An animal model of AOM caused by beta-lactamase-producing M. catarrhalis was established to study the course of this infection with the possibility of evaluating aspects of virulence between AOM pathogens. The AOM observed was a self-limiting disease. The results obtained in this study in a rat model support the continuing use of penicillins as first-line drugs in the treatment of AOM. Penicillins are not sufficient to treat all causative agents, but the majority of pathogens including the most virulent bacteria are eradicated from the middle ear.

Otitis media (OM), one of the commonest of childhood diseases, causes much suffering. OM exists in a variety of forms, two of which are acute otitis media (AOM) and otitis media with effusion (OME). The clinical courses of these conditions differ, AOM usually presenting with earache, fever and/or aural discharge, and the OME usually with hearing impairment. The tympanic membrane (TM) mirrors the events in the middle ear cavity, and pars flaccida (PF) is the initial site of inflammatory changes in the TM. PF is rich in mast cells (MCs), which by releasing various mediators, may trigger TM inflammation. The aims of the present studies were to investigate early inflammatory changes in the TM in rat models of OM; after mast cell degranulation, in response to AOM, and OME, after myringotomy in AOM and in normal ears. Furthermore, we developed a new rat AOM model, that excludes surgical trauma and resembles the natural route of infection in man. AOM and OME elicited the first inflammatory response in PF of the TM. The response to OME was discrete, but a slight increase in macrophages was found. During the first 48 hours of AOM, the inflammatory response was intense, following a bimodal pattern. This reaction is similar to that found after MC degranulation. In AOM, macrophages were the predominant cell in PF, while in pars tensa (PT), polymorphonuclear cells (mainly neutrophils) predominated. When myringotomy was performed in AOM ears, the healing time was shorter than that of myringotomy in normal ears. The highly inflamed lamina propria seemed to promote healing. During early AOM, as well as following myringotomy, fibrin extravasates into PF and PT. This fibrin deposition may be involved in regulating the inflammatory response. Repeated nasal challenge with the otitis media pathogen Streptococcus pneumoniae provoked AOM and concomitant TM stimulation reduced the number of AOM cases. This new rat AOM model has the advantage of avoiding trauma in the middle ear cavity, while eliciting an intense inflammatory response in the middle ear cavity (MEC).