Vesicular stomatitis virus (VSV) infection causes inhibition of host protein synthesis, in part by sequestering initiation factors required for mRNA cap recognition. The viral mRNAs share a common mRNA structure to those of the host cell, with a 5' cap and 3' polyadenylate tail, but continue to be efficiently translated despite host translational shutoff. This observation suggests that a non-canonical translation pathway is utilized for viral protein synthesis. To investigate this pathway, we performed an RNA interference screen to identify genes required for VSV replication. In contrast to bulk cellular translation, viral translation is hypersensitive to knockdown of a protein constituent of the 60S ribosomal subunit, rpL40. Depletion of rpL40 diminishes VSV protein synthesis by >90% and is restored through complementation with an siRNA-resistant mutant of rpL40. To delineate the mechanism by which rpL40 is required for viral protein synthesis, we reconstituted translation of VSV mRNA in yeast extracts in vitro. In the absence of rpL40, we show that the two ribosomal subunits fail to associate on VSV mRNA, and the small subunit does not scan to the initiation codon. Regulation by rpL40 occurs in context of the large subunit, providing direct evidence for translational control by the ribosome itself. This rpL40- dependent mechanism of translation initiation is broadly conserved within eukaryotes, governed solely through an RNA determinant, and is utilized by several viruses within the order Mononegavirales. To determine whether a subset of cellular transcripts also require rpL40 for translation, we identified polysome-associated mRNAs in yeast by deep sequencing. We demonstrate that in vitro and in vivo translation of candidate mRNAs, including factors involved in stress responses, are inhibited in the absence of rpL40. This finding suggests that rpL40 plays a critical role in transcript-specific translation during cellular stress. Collectively, our work identifies an alternative translation pathway that is specifically dependent on rpL40, revealing a previously unappreciated mechanism of protein synthesis regulation by the ribosome.

Aus dem Patientengut einer Fachklinik für Klein- und Heimtiere wurden 11 nicht vorbehandelte Katzen zwischen einem und zwölf Jahren mit mittel- bis hochgradiger Gingivo-Stomatitis ausgewählt. Diese wurden für zwölf Wochen (84 Tage) stationär aufgenommen und nach einem standardisierten Therapiekonzept behandelt: Am ersten Tag erfolgte nach dentalem Röntgen eine umfassende Zahnsanierung. An den Tagen 0, 14, 28, 42 und 84 wurde Interferon (Virbagen Omega® des Herstellers Virbac S.A.®, Carros Cedex, Frankreich) unter Sedation lokal, d.h. submukosal mit 1 ME/kg KGW injiziert. An den Tagen 56, 58, 60 und 62 erfolgte die Interferongabe systemisch. Begleittherapien wurde nach Bedarf eingesetzt, jedoch ohne die Verwendung von Glukokortikoiden und Hormonpräparaten. Verfüttert wurde ausschließlich Futter des Herstellers Royal Canin®, Köln, in den ersten 14 Tagen das Feuchtfutter Royal Canin convalescence support®, ab Tag 15 Royal Canin intestinal® Feucht- und Trockenfutter. An allen Behandlungstagen wurden zur qualitativen Virusbestimmung Tupferproben der am stärksten entzündeten Bezirke entnommen, die Maulhöhle nach einem festen System abfotografiert und die Veränderungen in Formblättern (Stärke der Faucites, Gingivitis, Buccostomatitis, Größe der Fläche und Art der Veränderung) und Grafik-charts festgehalten. Am ersten und letzten Tag wurden außerdem Biopsien zur quantitativen Bestimmung der Viruslast entnommen. Die Entwicklungen in folgenden Bereichen wurden anhand fixer Kriterien 14-tägig festgehalten: Allgemeinzustand, Schmerzen bei der Maulöffnung, Halitosis/zäher Speichel, Größe der Mandibularlymphknoten, Appetit, Schmerzen bei Futter-aufnahme oder Gähnen, Hypersalivation, Aktivität, Putztrieb und Zugänglichkeit. Die klinischen Verbesserungen waren bei allen Tieren schon nach 14 Tagen augenfällig. Der Hauptvorstellungsgrund der Besitzer, Appetitlosigkeit und Schmerzen bei der Futteraufnahme waren einer fast ungestörten Futteraufnahme gewichen, diese konnte in den folgenden Wochen kaum noch optimiert werden. Die entzündlichen Ulzerationen und Proliferationen der Maulhöhle halbierten sich innerhalb der ersten 14 Tage, nach 84 Tagen war der Heilungsprozess bei acht der elf Katzen abgeschlossen. Die persistierenden Proliferationen der restlichen Katzen waren allerdings nicht entzündlich und beeinflussten die Futteraufnahme nicht. Allgemeinzustand, Aktivität, Putztrieb und Zugänglichkeit stiegen bei zehn von elf Katzen bis zum 42. Tag etwa linear auf artspezifisches Normalniveau an und blieben hier konstant. Hypersalivation und Schwellung der Mandibularlymphknoten legte sich, so vorhanden, bei allen Tieren bis auf zwei innerhalb von 28 Tagen, bei diesen beiden war bis zum 84. Tag nur eine geringgradige Verbesserung zu beobachten. Nach der systemischen Vier-Tages-Therapie wurde ein erneutes Aufflackern der Gingivo-Stomatitis etwa auf das Niveau des 56. Tages beobachtet, allerdings ohne Folgen für die Verhaltensparameter. Eine Reduktion der Viruslast konnte trotz der eindrucksvollen Verbesserungen im klinischen Bereich in keinem Fall festgestellt werden. Die FIV/FeLV-positiven Katzen sprachen langfristig wesentlich schlechter auf das Therapiekonzept an als die übrigen Probanden. Daher gilt es bei diesen Tieren vor Interferoneinsatz kritisch zwischen den nicht unerheblichen Kosten und der zweifelhaften Prognose abzuwägen. Generell kann das Therapiekonzept Zahnsanierung – Interferon – Begleittherapie nach erfolgtem FIV/FeLV-Test bei der felinen Gingivo-Stomatitis als klinisch erfolgreich betrachtet werden.

Doctor of Philosophy / This thesis describes experiments which were carried out at the Institute of Dental Research in Sydney and within the Department of Prosthetic Dentistry at the United Dental Hospital of Sydney between February 1991 and May 1996. The study is concerned with finding practical means of treating chronic atrophic candidosis, also referred to as Candida-associated denture stomatitis and to this purpose two methods of denture disinfection are investigated, namely, sodium hypoclorite denture soak and microwave irradiation. Although the aetiology of denture stomatitis is generally considered to be multifactorial, there is sufficient evidence that Candida species and in particular C. albicans play an important role in the aetiology of the condition. In Chapter 1, therefore, the literature review, which provides relevant background information for the experiments to be described in later chapters, is primarily concerned with Candida species. The characteristics and distribution of Candida species are described and factors affecting the distribution of or Candida are discussed. The literature relating to the cause of chronic atrophic candidosis is vast and consequently a detailed description is given of Candida-associated denture stomatitis in the section concerned with oral diseases caused by Candida and their treatment. Each of the subsequent chapters, contains a brief literature review of material relevant to the subject of the particular chapter. Chapter 2 describes laboratory work to assess the effect of sodium hypochlorite on the adhesion of Candida species to oral surfaces and the ability of Candida to coaggregate with oral streptococci. The results showed that sodium hypochlorite decreased the ability of Candida species to adhere to both inert surfaces and BECs. However, coaggregation of Candida with streptococci was increased. Thus, hypochlorite if used as a denture soak may initially reduce the ability of Candida species to adhere to the denture surface and may therefore assist the treatment of denture stomatitis. The effects of hypochlorite on the characteristics of Candida species that are associated with tissue invasion are described in Chapter 3. The production of acid proteinase, the formation of germ tubes and presence of major cell wall proteins at 43 and 27 kDa are demonstrated. The ability of the whole cells of certain species of Candida to aggregate human platelets was assessed. The results showed that sodium hypochlorite did not affect proteinase production by Candida species but the rate of germ tube formation and the production of Candida cell wall proteins were increased. Hypochlorite did not affect the ability of certain Candida species to aggregate human platelets. Mechanisms to defend the host against candidal invasion are discussed and include platelet aggregation where aggregated platelets release antimicrobial factors that are active against Candida. Chapter 4 describes an in vitro study to test the effects of sodium hypochlorite and microwave irradiation on the survival of Candida species and oral streptococci on denture surfaces. The results showed that 0.02% sodium hypochlorite denture soak for 8 h will eliminate Candida species and reduce the growth of streptococci. However, microwaving of dentures at medium setting for 6 min will eliminate both Candida and streptococci. This information servers as baseline data for clinical assessments described in Chapters 7 and 8. Denture hygiene is an important factor in the prevention and treatment of Candida-associated denture stomatitis. Hence, a clinical study to assess the microbiology of denture plaque is described in Chapter 5. The results showed that denture plaque was composed mainly of Gram-positive streptococci with varying proportions of Gram-positive rods, Gram-negative cocci and rods and is similar to dental plaque. Candida was not always isolated and when detected constituted a very small proportion (< 1%) of the total aerobic bacterial count. The results of an investigation to test the effect of soft denture liners in lower dentures on the colonization of denture surfaces by Candida species and aerobic bacteria are given in Chapter 6. There was no significant difference in Candida /bacterial colonization of dentures with soft denture liners and those without liners. Chapter 7 describes a clinical study to test the efficiency of sodium hypochlorite (0.02%) over-night denture soak as an effective denture disinfecting agent. Treatment of dentures with hypochlorite over a trial period resulted in reductions of Candida and aerobic bacteria and although the reductions were not significant the effect over the trial period could be assessed. A significant finding was that for the palate, treatment with hypochlorite over the trial period prevented an increase in candidal load. Thus, sodium hypochlorite may function as an effective disinfecting agent when used as 0.02% denture soak for a prolonged period. A pilot study to assess the effectiveness of microwaving dentures for ten min (350 W, 240 MHz) as a potential method of denture disinfection is described in Chapter 8. For practical reasons the dentures were microwaved only once only and therefore the effect over a trial period could not be assessed. However, one treatment resulted in significant reductions in the levels of Candida and aerobic bacteria. These findings have indicated that future research should be carried out to test the effect of daily consecutive microwave treatments on candidal and bacterial growth. The general discussion in Chapter 9 summarizes the data presented in the previous chapters and from the findings conclusions are made concerning the prevention and treatment of Candida-associated denture stomatitis. The limitations of this thesis are recognized and some important aspects of the study are recommended for future research.

University, Diss., 2006--Giessen.

Zugl.: Giessen, Univ., Diss., 2006

Thesis (Ph. D.)--University of Washington, 2005. / Vita. Includes bibliographical references (leaves 84-100).

Made available in DSpace on 2015-07-22T20:49:57Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-07-28 / Mucosite oral é complicação comum no tratamento do câncer. A glicina demonstra efeito antiinflamatório, imunomodulador e citoprotetor. Este estudo tem como objetivo avaliar os efeitos da suplementação de glicina na reparação da mucosite oral induzida por 5-fluorouracil em hamster. Os animais foram divididos em dois grupos: grupo experimental (GI; n=20) e grupo controle (GII; n=20) ambos receberam injeção intraperitoneal de 5-fluorouracil no 1° e 3° dia. Os animais tiveram a sua bolsa jugal direita evertida e arranhada superficialmente no dia 3. O Grupo I, foi submetido ao tratamento com glicina a 5% por infusão intraperitoneal durante 7 dias e o Grupo II, recebeu placebo. A mucosa do GI e GII foi avaliada clinicamente, por meio de escore, no D3 e D7. Ao final do experimento a bolsa jugal dos animais de ambos os grupos foi retirada e avaliada segundo parâmetros histopatológicos e bioquímicos. Os grupos I e II apresentaram acentuado processo inflamatório durante o período inicial, segundo a avaliação clínica. No GI houve redução da severidade da mucosite, diminuição do processo inflamatório, cicatrização acelerada e redução da peroxidação lipídica quando comparado ao GII no final do experimento (p < 0,001). A suplementação com glicina demonstrou ser promissor instrumento para tratamento da mucosite, devido aos seus efeitos no processo inflamatório. Palavras chaves: Glicina; Estomatite; Fluoruracila; Cricetulus. / Oral mucositis is common complication in cancer treatment. Glycine shows a anti-inflammatory, immunomodulatory and cytoprotective. This study aims to evaluate the effects of supplementation of glycine in the repair of oral mucositis induced by 5-fluorouracil in hamsters. The animals were divided into two groups: experimental group (GI, n = 20) and control group (GII, n = 20) both received intraperitoneal injection of 5-fluorouracil in the days 1 and 3. The animals had their right pouch everted and scratched the surface on day 3. Group I was treated with glycine 5% by intraperitoneal infusion for 7 days and Group II, not supplemented. The mucosa of the GI and GII was evaluated clinically, by scoring in D3 and D7. At the end , the cheek pouch of animals from both groups was removed and evaluated by histopathological parameters and biochemical . Groups I and II showed marked inflammatory process during the initial period, according to clinical evaluation. In GI decreased the severity of mucositis, reduction of inflammation, accelerated healing and decreased lipid peroxidation when compared to GII at the end of the experiment. Supplementation with glycine proves to be a promising tool for treatment of mucositis due to its effectson the inflammatory process. / TEDE / BV UNIFESP: Teses e dissertações

Submitted by TULIO MORANDIN FERRISSE null (tuliomferrisse@gmail.com) on 2016-05-30T18:50:25Z No. of bitstreams: 1 DISSERTAÇÃO - FINAL.doc: 8888832 bytes, checksum: ca99c5983969f9477ae1a74714d6d280 (MD5) / Rejected by Ana Paula Grisoto (grisotoana@reitoria.unesp.br), reason: Solicitamos que realize uma nova submissão seguindo as orientações abaixo: A versão final da dissertação/tese deve ser submetida no formato PDF (Portable Document Format). O arquivo PDF não deve estar protegido e a dissertação/tese deve estar em um único arquivo, inclusive os apêndices e anexos, se houver. Por favor, corrija o formato do arquivo e realize uma nova submissão. Agradecemos a compreensão. on 2016-05-31T17:11:40Z (GMT) / Submitted by TULIO MORANDIN FERRISSE null (tuliomferrisse@gmail.com) on 2016-06-02T18:27:31Z No. of bitstreams: 2 DISSERTAÇÃO - FINAL.doc: 8888832 bytes, checksum: ca99c5983969f9477ae1a74714d6d280 (MD5) DISSERTAÇÃO_Mestrado_24_05_2016.pdf: 2063661 bytes, checksum: 945e0429ad165f9d8b64a9f65b91534a (MD5) / Approved for entry into archive by Ana Paula Grisoto (grisotoana@reitoria.unesp.br) on 2016-06-02T19:56:03Z (GMT) No. of bitstreams: 1 ferrisse_tm_me_arafo.pdf: 2063661 bytes, checksum: 945e0429ad165f9d8b64a9f65b91534a (MD5) / Made available in DSpace on 2016-06-02T19:56:03Z (GMT). No. of bitstreams: 1 ferrisse_tm_me_arafo.pdf: 2063661 bytes, checksum: 945e0429ad165f9d8b64a9f65b91534a (MD5) Previous issue date: 2016-03-31 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / O conceito de reação liquenóide ou interface liquenóide foi introduzido na dermatologia para definir diversas doenças inflamatórias da pele que apresentam características histopatológicas similares. Assim como a pele, a mucosa oral é afetada por uma variedade de lesões liquenóides orais (LLOs). As LLOs foram classificadas em: lesão liquenóide de contato; lesão liquenóide a medicamento; doença do enxerto-versus-hospedeiro e lesões liquenóides não classificáveis de aspecto liquen plano-like, como a estomatite ulcerativa crônica (EUC) recentemente descrita. Além da sobreposição de características entres as lesões que compõem este grupo, o líquen plano oral (LPO) representa o principal diagnóstico diferencial. Tradicionalmente, o diagnóstico das LLOs e do LPO depende da associação clínica e histopatológica, mas em vários casos, esta abordagem não oferece um diagnóstico confiável. As realizações de estudos clínicos e laboratoriais podem auxiliar no entendimento da etiopatogenia destas doenças e refinar a capacidade de diferenciar as LLOs. Diante disto, os objetivos específicos deste estudo foram: (1) Realizar uma revisão sistemática sobre EUC com ênfase específica nas características clínicas, histopatológicas e imunopatológicas desta condição recentemente descrita; e (2) Realizar um estudo prospectivo para avaliar as características clínicas e histopatológicas das LLOs. / The concept of lichenoid reaction or lichenoid interface was introduced in dermatology to define various inflammatory diseases of the skin that have similar histopathological features. Just as the skin and oral mucosa is affected by a variety of oral lichenoid lesions (OLLs). OLLs were classified as contact Lichenoides injury; drug Lichenoides injury; chronic graft versus host and not classifiable lichenoid lesions aspect lichen planus-like, such as chronic ulcerative stomatitis (CUS) recently described. Besides the overlapping features among injuries that make up this group, oral lichen planus (OLP) is the main differential diagnosis. Traditionally, the diagnosis of OLLs and the OLP depends on the clinical and histopathological association, but in many cases, this approach does not provide a confident diagnosis. The achievement of clinical and laboratory studies may help to understand the pathogenesis of these diseases and refine the ability to differentiate OLLs. Thus, the specific objectives of this study were: (1) conduct a systematic review of CUS with particular emphasis on clinical, histopathological and immunopathological of this newly described condition; and (2) Conducting a prospective study to evaluate the clinical and histopathological characteristics of OLLs.

Magister Scientiae Dentium - MSc(Dent) / Candida albicans is a clinical fungal isolate that is most frequently isolated from different host niches, and is implicated in the pathogenesis of several fungal infections, including oral candidiasis. The pathogenesis and antifungal resistance mechanisms of Candida species are complex and involve several pathways and genes. Oral candidiasis incidence rates are rapidly increasing, and the increase in resistance to conventional antifungals has led to the need to develop innocuous and more efficacious treatment modalities. The purpose of this study was to explore a single pot process for phytosynthesis of zinc oxide nanoparticles (GZnO NPs) and to assess their antifungal potential.

Orientador: Andreia Bufalino / Resumo: O conceito de reação liquenóide ou interface liquenóide foi introduzido na dermatologia para definir diversas doenças inflamatórias da pele que apresentam características histopatológicas similares. Assim como a pele, a mucosa oral é afetada por uma variedade de lesões liquenóides orais (LLOs). As LLOs foram classificadas em: lesão liquenóide de contato; lesão liquenóide a medicamento; doença do enxerto-versus-hospedeiro e lesões liquenóides não classificáveis de aspecto liquen plano-like, como a estomatite ulcerativa crônica (EUC) recentemente descrita. Além da sobreposição de características entres as lesões que compõem este grupo, o líquen plano oral (LPO) representa o principal diagnóstico diferencial. Tradicionalmente, o diagnóstico das LLOs e do LPO depende da associação clínica e histopatológica, mas em vários casos, esta abordagem não oferece um diagnóstico confiável. As realizações de estudos clínicos e laboratoriais podem auxiliar no entendimento da etiopatogenia destas doenças e refinar a capacidade de diferenciar as LLOs. Diante disto, os objetivos específicos deste estudo foram: (1) Realizar uma revisão sistemática sobre EUC com ênfase específica nas características clínicas, histopatológicas e imunopatológicas desta condição recentemente descrita; e (2) Realizar um estudo prospectivo para avaliar as características clínicas e histopatológicas das LLOs. / Abstract: The concept of lichenoid reaction or lichenoid interface was introduced indermatology to define various inflammatory diseases of the skin that have similarhistopathological features. Just as the skin and oral mucosa is affected by a variety oforal lichenoid lesions (OLLs). OLLs were classified as contact Lichenoides injury;drug Lichenoides injury; chronic graft versus host and not classifiable lichenoidlesions aspect lichen planus-like, such as chronic ulcerative stomatitis (CUS) recentlydescribed. Besides the overlapping features among injuries that make up this group,oral lichen planus (OLP) is the main differential diagnosis. Traditionally, the diagnosisof OLLs and the OLP depends on the clinical and histopathological association, butin many cases, this approach does not provide a confident diagnosis. Theachievement of clinical and laboratory studies may help to understand thepathogenesis of these diseases and refine the ability to differentiate OLLs. Thus, thespecific objectives of this study were: (1) conduct a systematic review of CUS withparticular emphasis on clinical, histopathological and immunopathological of thisnewly described condition; and (2) Conducting a prospective study to evaluate theclinical and histopathological characteristics of OLLs. / Mestre