Thesis (doctoral)--Lund University, 1993. / Added t.p. with thesis statement inserted.

Thesis (doctoral)--Lund University, 1995. / Added t.p. with thesis statement inserted.

Source: Masters Abstracts International, Volume: 47-01, page: 0318. Adviser: Janice Cormier. Includes bibliographical references

Thesis (doctoral)--Lund University, 1993. / Added t.p. with thesis statement inserted.

Thesis (doctoral)--Lund University, 1995. / Added t.p. with thesis statement inserted. Includes bibliographical references.

No description available.

Durante uma infecção, uma complexa seqüência de eventos é inkiada após a invasão do hospedeiro por microrganismos patogênicos. Escherichia coli enteroinvasora (EIEC), assim como Shigella, causa disenteria através da invasão da mucosa do cólon, levando à destruição tecidual e inflamação. Para que ocorra um processo infeccioso, porém, são necessários inóculos de 102 Shigella e 106 EIEC. Foram avaliados aspectos da resposta inflamatória desencadeada pela infecção por EIEC em modelo murino, comparativamente a Shigella. A infecção de macrófagos J774 por EIEC resultou em fagocitose bacteriana, comprometimento da viabilidade do macrófago e produção de citocinas. Macrófagos de camundongos C57BU6 infectados com EIEC produziram NO, que parece ser importante no controle da infecção. Foi observado que camundongos INOS nocaute apresentaram maior produção de citocinas pró-inflamatórias e maior letalidade após infecção do que os selvagens. EIEC induziu a migração de granulócitos e monócitos para o peritônio, e a secreção de citocinas por estas células. Houve proliferação de linfócitos em resposta aos antígenos solúveis de EIEC, mas não foi detectada produção de citocinas por estes linfócitos.Comparativamente a Shigella, EIEC escapou mais lentamente do macrófago, induziu menor produção de citocinas pró-inflamatórias e NO, e menor ativação dos linfócitos T. Estes dados sugerem o desafio com EIEC desencadeia uma resposta menos severa no hospedeiro do que Shigella, o que explicaria a forma mais branda de disenteria e resolução mais rápida do processo infeccioso causado por EIEC. / During an infection, a complex sequence of events in iniciated after invasion of the host by pathogenic microorganisms. Enteroinvasive Escherichia coli (EIEC) and Shigella cause dysentery by means of invading the colonic mucosa, leading to tissue destruction and inflammation. In arder for an infectious process to occur, inocula of 102 Shigella are necessary incontrast to e 106 EIEC. The infection of J774 macrophages by EIEC resulted in phagocytosis of the bacterium, a hindering of the viability of the macrophage and in the production of cytokines. Macrophages obtained from C57BU6 mice infected with EIEC produced NO, which seems to be important for the control if infection. We observed that in iNOS knockout mice, both the production of proinflammatory cytokines and lethality were higher than that observed in wild-type mice. EIEC induced the migration of granulocytes and monocytes to the peritoneum as well as the secretion of cytokines by these cells. We observed a proliferation of Iymphocytes in response to inoculation with soluble EIEC antigens, however, in this case, the production of cytokines was not detected. Compared to Shigella, EIEC was slower in escaping from the macrophage, and induced a shyer production of pro-inflammatory cytokines and NO, as well as promoted a smaller activation of T Iymphocytes. These data suggest that when challenged with EIEC, the host produces a less severe response than that elicited by Shigella, which might explain why the infectious process with EIEC produces a milder form of dysentery with a quicker resolution.

O Staphylococcus aureus é um patógeno extremamente versátil tanto em termos de resistência a antimicrobianos quanto em virulência. O S. aureus resistente a oxacilina (ORSA) adquire a resistência a toda a classe de beta-Iactâmicos através de um cassete cromossômico (SCCmec) que carrega o gene mecA, mas pode carregar outros genes de resistência. A soma desses genes de resistência e de virulência torna o S. aureus um grave problema para hospitais do mundo inteiro, que nos últimos vem se estendendo também à comunidade. Foram estudados 50 isolados de ORSA, dentre os quais 15 pertencentes ao clone endêmico brasileiro (CEB) e 3 cepas SCCmec tipo IV isoladas entre 1995 e 1999. Adicionalmente, 32 amostras ORSA SCCmec tipo IV isoladas no Hospital de Clínicas de São Paulo. As amostras foram analisadas quanto ao perfil de sensibilidade a antimicrobianos, classificação do tipo de SCCmec, perfil de virulência quanto a toxinas e adesinas, classificação do grupo agr (locus regulatório dos genes de virulência) e sua funcionalidade, avaliação da expressão dos genes de toxinas e genotipagens por PFGE e MLST. Observou-se que as cepas CEB são multiresistentes. Já as cepas SCCmec IV apresentam um perfil de sensibilidade maior, uma vez que possuem um tipo de SCCmec que não carrega outros genes de resistência além do gene mecA. As amostras CEB SCCmec IV não apresentaram grandes diferenças no conteúdo de toxinas e adesinas. Apenas as cepas SCCmec IV isoladas entre 1995 e 1999 apresentaram um maior conteúdo de genes de virulência que as isoladas no HC. As cepas SCCmec IV isoladas no Brasil não são altamente virulentas como descrito em outros países. Não possuem fatores de virulência como a Leucocidina Panton-Valentine, toxinas exfoliativas e enterotoxinas. Por outro lado, possuem a alfa-hemolisina e a leucocidina LukD-LukE, toxina ainda pouco estudada, que vem sendo apresentada em pesquisas como causa de lesões oculares graves e diarréias pós-antibioticoterapia. Não foi possível estabelecer uma relação entre o tipo de agr e o perfil de virulência das cepas, uma vez que os perfis foram muito semelhantes mesmo entre cepas de grupos agr diferentes. / Staphylococcus aureus is an extremely successful pathogen for it is both highly resistant to antibiotics in addition to being virulent. Methicillin-resistant Staphylococcus aureus (MRSA) acquires resistance to the beta-Iactam antibiotics through the acquisition of a chromosomal cassette (SCCmec) which carries the mecA gene, and can carry other resistance genes. The presence of these genes in S. aureus makes it a serious problem in hospitaIs worldwide. In spite of usually being restricted to the nosocomial environment, over the last few years MRSA has been spreading throughout the community. Fifty nosocomial MRSA strains were studied, including 15 belonging to the Brazilian endemic clone (BEC), 3 type IV SCCmec strains isolated between 1995-1999, and 32 type N SCCmec isolates from the \"Hospital de Clínicas (HC) de São Paulo\". The isolates were analyzed as to their susceptibility profile, SCCmec type, virulence and expression profile (toxins and adhesins), agr group classification and functionality, PFGE and MLST profiles. BEC isolates proved to be multiresistant to antibiotics. Type IV SCCmec strains presented a susceptibility profile to a number of drugs of different antimicrobial classes. BEC and type N SCCmec strains did not present significant differences in their virulence profiles. Only the type IV SCCmec strains isolated in 1995-1999 presented a greater virulence profile than those isolated in the HC. Type IV SCCmec strains isolated in Brazil were not highly virulent as described in other countries. Brazilian isolates usually do not possess virulence factors such as the Panton-Valentine leukocidin, exfoliative toxins and enterotoxins. On the other hand, they usually possess alpha-hemolysin and the LukED leukocidin, which is still very poorly studied that have been presented in papers like cause of serious ocular lesions and post-antimicrobial therapy diarrhea. A relation between the agr type and the virulence profile was not established, for virulence profiles were very similar even between isolates belonging to different agr groups.

Antimicrobial resistance is a worldwide problem that has deleterious long-term effects as the development of drug resistance outpaces the development of new drugs. Plants have been used for many generations for healing purposes, and screening of extracts of these plants has often yielded positive outcomes. This study was aimed at isolating and characterizing the major active antimicrobial compounds present in the stem bark of C. molle, in a bid to identify potential sources of cheap starting materials for the synthesis of new drugs. Various solvents (hexane, ethyl acetate, dichloromethane, acetone, ethanol and methanol) were used for extraction. The agar well diffusion technique was used to screen for antimicrobial activity of C. molle extracts against Streptococcus pyogenes ATCC 49399, Plesiomonas shigelloides ATCC 51903, Pseudomonas aeruginosa ATCC 15442, Helicobacter pylori ATCC 43526 and Helicobacter pylori 252C (clinical isolate); minimum inhibition concentration (MIC) of the most active extracts was determined by the broth dilution method. Fractionation of acetone extract was done by thin layer chromatography (TLC) and bioautography to determine the compounds present and their antimicrobial activity respectively. The acetone extract was purified by column chromatography and their MIC determined. The most potent fraction (EA4) was subjected to Gas chromatography- Mass spectrometry (GC-MS) and High performance liquid chromatography (HPLC) for identification of the active compounds. Results were analyzed by the Fisher‟s exact test. All the extracts tested demonstrated antimicrobial activity with zone diameters of inhibition ranging from 0–32 mm. Acetone was the most potent extract with its MIC ranging from 0.078–5.0 mg/mL. Seventeen fractions were collected from column chromatography and the most active fraction against all the organisms was EA 4 (eluted with 100 percent ethyl acetate), with its MIC ranging from 0.078 - 2.5mg/mL. There was no statistically significant difference (P>0.05) in the potency of the xii four extracts (acetone, methanol, ethanol and ethyl acetate) and antibiotic (ciprofloxacin) on the different bacterial strains tested, likewise the crude extract and the fractions. No compound was detected by GC-MS whereas numerous peaks were identified by HPLC implying that the active compounds in this plant are non volatile. We could not identify the compounds thereby proposing further studies using Nuclear magnetic resonance to identify the compounds. The study revealed that the acetone extract of C. molle was the most active against all the test organisms and therefore justifies the use of this plant in traditional medicine.

Abstract Acute rhinosinusitis (ARS) is a common condition often treated with antibiotics, even though the cause is usually viral. Despite the commonness of ARS, there is limited evidence on the development and diagnosis of bacterial cases. So far, we lack prospective studies where the bacterial cause would have been confirmed with a bacterial culture of the paranasal sinus aspirate. The purpose of the study was to investigate the course of ARS with a prospective inception cohort study among young adults with ARS, using sequential and standardized methods. To differentiate viral and bacterial ARS, maxillary sinus aspiration and a bacterial culture were used as a reference standard for bacterial ARS. Fifty conscripts with ARS were recruited between February and April 2012. Eight patients (16%) had a positive culture from the maxillary sinus aspirate at 9–10 days and thus, had bacterial ARS. Viral and bacterial coinfection resulted in extensive paranasal mucosal abnormalities and increased symptoms during the episode. The paranasal mucosal abnormalities developed rapidly and remained relatively constant during the episode in both bacterial and non-bacterial ARS. A change in inflammatory biomarker levels indicated both local and systemic inflammatory responses, which were strongest at the onset of symptoms. Symptoms or their changes were of little use in diagnosing bacterial ARS, but secretion seen in the nasal cavity, posterior pharynx or middle meatus predicted bacterial ARS quite well. These results suggest that bacterial infection may modify symptoms and paranasal abnormalities already at the beginning of an ARS episode, although the spread of paranasal abnormalities may not be an etiological factor in the development of bacterial ARS. ARS involves local and systemic inflammatory responses, which are strongest at the beginning of the episode. Examination of the nose and throat is recommended for diagnosing bacterial ARS. / Tiivistelmä Nenän äkillinen sivuontelotulehdus on tavallinen tauti, jonka hoitoon käytetään paljon antibiootteja, vaikka sen aiheuttaja on useimmiten virus. Bakteerin aiheuttaman tautimuodon kehittymisestä ja diagnostiikasta ei ole julkaistu tutkimuksia, joissa potilaita olisi seurattu taudin alusta lähtien ja bakteerin olemassaolo olisi varmistettu nenän sivuontelosta otetulla bakteerinäytteellä. Tämän väitöskirjatyön tarkoituksena oli selvittää nenän äkillisen sivuontelotulehduksen kulkua käyttämällä toistuvia, standardisoituja menetelmiä. Bakteerin aiheuttama tauti todettiin poskiontelopistolla ja bakteeriviljelyllä. Tutkimukseen osallistui viisikymmentä (50) äkilliseen ylähengitystieinfektioon sairastunutta varusmiestä keväällä 2012. Kahdeksalla (16 %) potilaalla todettiin bakteerin aiheuttama tauti poskiontelopiston avulla 9–10 päivää oireiden alkamisen jälkeen. Viruksen ja bakteerin sekainfektio aiheutti laajemmat sivuonteloiden tulehduslöydökset ja voimakkaammat oireet kuin pelkän viruksen aiheuttama tauti. Sivuonteloiden tulehduslöydökset kehittyivät nopeasti ja pysyivät sekä bakteerin että viruksen aiheuttamassa taudissa varsin muuttumattomina. Tulehdusmerkkiaineiden muutokset osoittivat sekä paikallisen, että yleisen tulehdusreaktion, jotka olivat voimakkaimmillaan taudin alussa. Oireet tai niissä taudin aikana tapahtuneet muutokset eivät osoittautuneet hyviksi merkeiksi bakteerin aiheuttaman taudin toteamiseksi, mutta eritteen näkyminen nenässä, nielussa tai keskikäytävässä ennakoi hyvin bakteerin aiheuttaman sivuontelotulehduksen toteamista. Bakteeri saattaa vaikuttaa oireisiin ja sivuonteloiden tulehduslöydöksiin jo nenän äkillisen sivuontelotulehduksen alussa, mutta tulehduslöydösten laajuus ei välttämättä liity bakteerin aiheuttaman taudin kehittymiseen. Nenän äkilliseen sivuontelotulehdukseen liittyy paikallinen ja yleinen tulehdusreaktio, jotka ovat voimakkaimmillaan taudin alussa. Potilaan nenän ja nielun tutkiminen on tärkeää bakteerin aiheuttaman nenän sivuontelotulehduksen toteamiseksi.