Diss. (sammanfattning) Stockholm : Karol. inst., 2004. / Härtill 5 uppsatser.

<p>Urinary tract infections (UTIs) are typically caused by bacteria that colonize different regions of the urinary tract, mainly the bladder and the kidney. Approximately 25% of women that suffer from UTIs experience a recurrent infection within 6 months of the initial bout, making UTIs a serious economic burden resulting in more than 10 million hospital visits and $3.5 billion in healthcare costs in the United States alone. Type-1 fimbriated Uropathogenic E. coli (UPEC) is the major causative agent of UTIs, accounting for almost 90 % of bacterial UTIs. The unique ability of UPEC to bind and invade the superficial bladder epithelium allows the bacteria to persist inside epithelial niches and survive antibiotic treatment. Persistent, intracellular UPEC are retained in the bladder epithelium for long periods, making them a source of recurrent UTIs. Hence, the ability of UPEC to persist in the bladder is a matter of major health and economic concern, making studies exploring the underlying mechanism of UPEC persistence highly relevant. </p><p>In my thesis, I will describe how intracellular Uropathogenic E.coli (UPEC) evade host defense mechanisms in the superficial bladder epithelium. I will also describe some of the unique traits of persistent UPEC and explore strategies to induce their clearance from the bladder. I have discovered that the UPEC virulence factor Alpha-hemolysin (HlyA) plays a key role in the survival and persistence of UPEC in the superficial bladder epithelium. In-vitro and in-vivo studies comparing intracellular survival of wild type (WT) and hemolysin deficient UPEC suggested that HlyA is vital for UPEC persistence in the superficial bladder epithelium. Further in-vitro studies revealed that hemolysin helped UPEC persist intracellularly by evading the bacterial expulsion actions of the bladder cells and remarkably, this virulence factor also helped bacteria avoid t degradation in lysosomes. </p><p>To elucidate the mechanistic basis for how hemolysin promotes UPEC persistence in the urothelium, we initially focused on how hemolysin facilitates the evasion of UPEC expulsion from bladder cells. We found that upon entry, UPEC were encased in “exocytic vesicles” but as a result of HlyA expression these bacteria escaped these vesicles and entered the cytosol. Consequently, these bacteria were able to avoid expulsion by the cellular export machinery. </p><p>Since bacteria found in the cytosol of host cells are typically recognized by the cellular autophagy pathway and transported to the lysosomes where they are degraded, we explored why this was not the case here. We observed that although cytosolic HlyA expressing UPEC were recognized and encased by the autophagy system and transported to lysosomes, the bacteria appeared to avoid degradation in these normally degradative compartments. A closer examination of the bacteria containing lysosomes revealed that they lacked V-ATPase. V-ATPase is a well-known proton pump essential for the acidification of mammalian intracellular degradative compartments, allowing for the proper functioning of degradative proteases. The absence of V-ATPase appeared to be due to hemolysin mediated alteration of the bladder cell F-actin network. From these studies, it is clear that UPEC hemolysin facilitates UPEC persistence in the superficial bladder epithelium by helping bacteria avoid expulsion by the exocytic machinery of the cell and at the same time enabling the bacteria avoid degradation when the bacteria are shuttled into the lysosomes. </p><p>Interestingly even though UPEC appear to avoid elimination from the bladder cell their ability to multiple in bladder cells seem limited.. Indeed, our in-vitro and in-vivo experiments reveal that UPEC survive in superficial bladder epithelium for extended periods of time without a significantly change in CFU numbers. Indeed, we observed these bacteria appeared quiescent in nature. This observation was supported by the observation that UPEC genetically unable to enter a quiescence phase exhibited limited ability to persist in bladder cells in vitro and in vivo, in the mouse bladder. </p><p>The studies elucidated in this thesis reveal how UPEC toxin, Alpha-hemolysin plays a significant role in promoting UPEC persistence via the modulation of the vesicular compartmentalization of UPEC at two different stages of the infection in the superficial bladder epithelium. These results highlight the importance of UPEC Alpha-hemolysin as an essential determinant of UPEC persistence in the urinary bladder.</p> / Dissertation

Orientador: Luiz Fernando de Oliveira e Silva Carvalho / Banca: Maria Cristina Thomaz / Banca: Geraldo Camilo Alberton / Resumo: As infecções urinárias (IU) em porcas estão entre as principais causas de falhas reprodutivas que influem na produtividade do rebanho, proporcionando grandes prejuízos econômicos. No presente trabalho foram testados dois acidificantes urinários - o ácido cítrico e o cloreto de amônio e cloreto de sódio, de modo a comparar a atividade destes produtos, no controle de cistites em matrizes suínas. Utilizaram-se 53 porcas adultas, gestantes ou não, de linhagens comerciais, portadoras ou não de cistite, sendo identificados os animais sadios ou afetados com base nos resultados de urinálises e cultivos bacterianos. O primeiro ensaio foi constituído de duas fases - fase 1 - realizada com 25 fêmeas em início de gestação (20 com cistite e 5 sadias), alimentadas com ração de gestação e fase 2 - realizada com 20 animais em final de gestação (16 com cistite e 4 sadias), alimentadas com ração de lactação. O pH, a densidade e a contagem bacteriana nas amostras de urina foram as variáveis estudadas. No segundo ensaio foram utilizadas 8 porcas, todas com cistite e não gestantes. A quatro delas administrou-se ração com cloreto de amônio e outras quatro receberam ração não suplementada com o produto. Avaliou-se o consumo de água, a produção de urina, os pH da urina e do sangue. Os resultados demonstraram que o ácido cítrico determinou diminuição do número de unidades formadoras de colônias, porém não interferiu no pH e densidade urinária dos animais. O cloreto de amônio reduziu o pH urinário demonstrando ação acidificante mesmo colhendo a urina 24 horas após o arraçoamento, porém não interferiu nas densidade e contagem bacteriana. Com relação o cloreto de sódio (1,5% ou 52,5 g/Kg de ração) não se observou qualquer efeito sobre os parâmetros estudados (pH urinário, densidade e contagem bacteriana). / Abstract: The urinary infections(IU) in sows are among the main causes of reproductive imperfections that influence in the productivity of the flock, providing great economic damages. In the present work two acidifiers were tested out - acid citric and the chloride of ammonium and sodium chloride, in order to compare the activity of these products, in orther to control the cystitis in swine. 53 adult, pregnants and non pregnant sows were used , of tradeable ancestries, bearing, donþt bearing cystitis being identified the healthy or affected animals on the basis of the bacterial results of urinalysis culture. The first assay was carried out into two phases - phase 1 - carried through with 25 females in theirs early gestation (20 with cystitis and 5 healthy ones), fed gestation diet and phase 2 - carried through with 20 animals in gestation end (16 with cystitis and 4 healthy ones), fed with lactation ration. pH, the density and the number of CFUs in the urinary samples were the studied. As the assay 8 sows had been held envolving, all cystitis and not pregnant. Four out of 8 sows were fed with chrolide ammonium based rations. The remnants 4 were fed with no supplemented feed. The consumption of water, urinary output, urinary pH and the blood were also evaluated. The results showed that the citric acid determined a decrease in the CFU. However, it didnþt interfere at both pH and urinary density in the animals. The ammonium chloride reduced the urinary pH showing acidifying action even while collecting the urine after a period of 24 hours after the feeding time. Both density and CFU were not changed. Regarding the sodium chloride (1.5% or 52.5g/kg) nothing was found out within the complying parameters (pH urinary, dendity and CFU). / Mestre

Šlapimo organų infekcija (ŠOI) vaikams yra antra pagal dažnį po kvėpavimo organų infekcijų. Tai dažniausia vaikų nefrologinė liga. ŠOI iki 3–6 mėn. amžiaus dažniau serga berniukai, vyresniame amžiuje – mergaitės. Priešmokykliniame amžiuje mergaitės simptomine šlapimo organų infekcija serga 6–20 kartų dažniau nei berniukai. Beveik kas trečia moteris iki 24 metų ŠOI yra sirgusi bent vieną kartą, o per gyvenimą ŠOI yra sirgusi beveik kas antra moteris. ŠOI linkusi pasikartoti. Kartojantis ŠOI, liga gali įgauti lėtinę eigą, sukelti inkstų randėjimą, lėtinį inkstų funkcijos nepakankamumą (IFN), nulemti hipertenzijos atsiradimą, o moterims – nėštumo komplikacijas. 29 % vaikų, kuriems buvo atliktos inkstų transplantacijos, inkstų pažeidimas buvo sąlygotas pielonefrito ar intersticinio nefrito. Lietuvoje vaikų lėtinio IFN priežastis 31,7 proc. obstrukcinė nefropatija ir lėtinis pielonefritas. Kol nebuvo taikomas profilaktinis gydymas, 60 proc. mergaičių ir 20 proc. berniukų ŠOI pasikartodavo jau pirmaisiais metais po pirmos ŠOI. Taikant profilaktinį gydymą, 1 m. laikotarpyje po persirgtos ŠOI. infekcijos pasikartojimas sumažėjo iki 15 proc. Mažo amžiaus vaikams ŠOI pasikartojimą dažniausiai lemia įgimtos šlapimo organų anomalijos. Dauguma jaunesnio mokyklinio amžiaus vaikų, kuriems yra pasikartojanti ŠOI, turi organiškai nepakitusius šlapimo organus. Pastaruoju metu atliekamos studijos, kurių tikslas nustatyti elgesio ir funkcinių sutrikimų vertę ŠOI pasikartojimui, tačiau duomenys... [toliau žr. visą tekstą] / Urinary tract infection (UTI) is one of the most common bacterial diseases in childhood. Recurrent UTI occurs in 20 – 86% of children. Recurrent UTI is relatively frequent in girls. At the age of 7, the prevalence of recurrent UTI in boys population is 1%, in girls population – 5%. Nearly one of three women will have at least one episode of UTI requiring antimicrobial therapy by the age of 24 years. Almost half of all women will experience one UTI during their lifetime. It is known, that in the group of young children the most common reason of recurrent UTI is anatomic abnormalities, such as vesicoureteral reflux (VUR), hydronephrosis. However, not all recurrent UTI can be explained by anatomic abnormalities. The vast majority of school age children with recurrent UTI have anatomically normal urinary tract. We found changes in urodynamic investigation for 91.4% of children with recurrent urinary tract infection at the age of 5–18. Having a history of previous recurrent UTI is a strong risk factor for having subsequent UTI. Antibacterial characteristics of urine and other host defence mechanisms may be important signs associated with UTI risk, but have not been clearly shown to be associated with UTI in healthy persons. Recent studies discuss about the role of behavioural and functional abnormalities (inadequate fluid intake, stool retention, infrequent voiding, etc.) that can predispose recurrent urinary tract infections. Influence of some these abnormalities for recurrent... [to full text]

Interstitial Cystitis / Painful Bladder Syndrome (IC/PBS) is a persistent and refractory medical condition that is characterized by chronic pelvic pain along with abnormal urinary frequency and urgency. There is no widely accepted etiology or efficacious cure for IC/PBS, thus treatment often relies on pain and symptom management. IC/PBS is associated with strong functional disability but theoretical models of disability have yet to be tested with these patients. As well, psychosocial factors associated with various IC/PBS outcomes (i.e., depression, catastrophizing, social support) are also associated with disability in a variety of chronic painful medical conditions but remain untested in disability models for IC/PBS. Thus, this research evaluated psychosocial factors as potential mediators of disability within the Disablement Process Model. Female patients diagnosed with IC/PBS by a urologist in a tertiary care hospitals were recruited (n=196; females). In using structural equation modeling of a final IC/PBS disability model, negative affect and catastrophizing were found to be partial mediators on the relationship between impairments and functional disability and social support was not a significant mediator of disability. Negative affect and catastrophizing may be key psychosocial factors in IC/PBS disability. Research implications for the Disablement Process Model and potential clinical interventions are discussed in light of the current findings. / Thesis (Master, Psychology) -- Queen's University, 2011-08-29 14:18:29.478

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 4 uppsatser.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2010.

Thesis (Ph. D.)--Ohio State University, 2005. / Title from first page of PDF file. Document formatted into pages; contains xii, 153 p.; also includes graphics (some col.) Includes bibliographical references (p. 132-153). Available online via OhioLINK's ETD Center

A cistite hemorrágica (CH) consiste em um processo inflamatório difuso de origem infecciosa ou não que resulta em um sangramento da mucosa vesical. As CH crônicas recorrentes induzidas pela ciclofosfamida (CYP) são um desafio na prática clínica pela alta morbidade e por vezes mortalidade dos pacientes. O tratamento da CH induzida pela ciclofosfamida consiste no uso de MESNA, disulfiram, N-acetil-cisteína, anti-inflamatório, oxigênio hiperbárico, hiper-hidratação e irrigação vesical, mas novas terapias têm sido investigadas, inclusive usando produtos naturais. A espécie vegetal Chenopodium ambrosioides L., conhecida popularmente como mastruz, mastruço e erva-de-Santa-Maria, tem sido relatada pela população como anti-inflamatório e analgésico. O presente estudo investigou os efeitos do extrato bruto hidroalcoólico de folhas de Chenopodium ambrosioides na CH induzida pela ciclofosfamida em ratos. Vinte e nove ratos receberam 150 mg/kg de CYP por via intraperitoneal (i.p.) para indução de CH e em seguida foram divididos em três grupos: controle negativo (CN), tratados com soro fisiológico a 0,9%; extrato bruto hidroalcoólico de Chenopodium ambrosioides (EBHCa), tratado com dose única de 50 mg/kg de extrato bruto hidroalcoólico de Chenopodium ambrosioides (EBH) e controle positivo (CP), tratados com dose única de 15 mg/kg de diclofenaco de potássio, todos por gavagem. Após 48 horas da indução da CH os animais foram sacrificados para retirada da bexiga, que foi preparada para análise histopatológica e imuno-histoquímica. O EBH foi capaz de diminuir o peso da bexiga e histologicamente a inflamação aguda e crônica da bexiga, a extensão do infiltrado inflamatório na parede vesical e a neoformação capilar do mesmo modo que o diclofenaco de potássio, quando comparados ao grupo CN. Observou-se ainda uma redução da expressão imuno-histoquímica de cicloxigenase-2 (COX-2) e do fator nuclear kappa B (NF&#61547;B) na bexiga. No presente estudo o EBH das folhas de Chenopodium ambrosioides apresentou atividade anti-inflamatória, semelhante ao diclofenaco de potássio, no tratamento da CH induzida pela CYP. / Hemorrhagic cystitis (HC) consists of a diffuse inflammatory process that results on the bleeding of the bladder mucosa due to infectious or noninfectious etiology. Chronically recurrent CYP induced HC remains a challenge to clinical practice given its high morbidity and sometimes mortality of patients. Treatment consists of administering MESNA, disulfiram, N-acetylcysteine, anti-inflammatory, hyperbaric oxygen, hyperhydration and bladder irrigation, though new therapies have been investigated, such as the use of natural products. Popularly known as mastruz, mastruço and erva-de-Santa-Maria, Chenopodium ambrosioides L. has been generally reported by people as having anti-inflammatory and analgesic effects. The following study investigated the effects of a hydroalcoholic crude extract (EBH) of Chenopodium ambrosioides leaves on cyclophosphamide (CYP) induced HC in rats. In order to induce HC, twenty nine rats were intraperitoneally (i.p.) administered 150mg/kg of CYP and then divided into three groups: negative control (NC) were treated with 0,9% saline solution; hydroalcoholic crude extract of Chenopodium ambrosioides (EBHCa) were treated with a single dose of 50 mg/kg of EBH administered and positive control (PC) were treated with a single dose of 15 mg/kg of diclofenac potassium, all of them by gavage. After 48 hours of HC induction, all rats were sacrificed, their bladders removed and prepared for histopathological and immunohistochemical analysis. EBH was able to decrease bladder weight and histologically decrease acute and chronic bladder inflammation, decrease on the infiltrated inflammatory extension of the bladder wall and capillary neoformation in the same way of those from group CN. There was also a reduction in the immunohistochemical expression of cyclooxygenase-2 (COX-2) and nuclear factor kappa B (NF&#61547;B) in the bladder. In this study, Chenopodium ambrosioides leaves EBH showed anti-inflammatory activity which was similar to results from diclofenac potassium used on treatment of CYP induced HC.

Made available in DSpace on 2014-06-11T19:23:46Z (GMT). No. of bitstreams: 0 Previous issue date: 2006-07-07Bitstream added on 2014-06-13T20:11:38Z : No. of bitstreams: 1 meister_ar_me_jabo.pdf: 286547 bytes, checksum: e9bc3ab4d6f06ec0fdb7ea88faaca642 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / As infecções urinárias (IU) em porcas estão entre as principais causas de falhas reprodutivas que influem na produtividade do rebanho, proporcionando grandes prejuízos econômicos. No presente trabalho foram testados dois acidificantes urinários - o ácido cítrico e o cloreto de amônio e cloreto de sódio, de modo a comparar a atividade destes produtos, no controle de cistites em matrizes suínas. Utilizaram-se 53 porcas adultas, gestantes ou não, de linhagens comerciais, portadoras ou não de cistite, sendo identificados os animais sadios ou afetados com base nos resultados de urinálises e cultivos bacterianos. O primeiro ensaio foi constituído de duas fases - fase 1 - realizada com 25 fêmeas em início de gestação (20 com cistite e 5 sadias), alimentadas com ração de gestação e fase 2 - realizada com 20 animais em final de gestação (16 com cistite e 4 sadias), alimentadas com ração de lactação. O pH, a densidade e a contagem bacteriana nas amostras de urina foram as variáveis estudadas. No segundo ensaio foram utilizadas 8 porcas, todas com cistite e não gestantes. A quatro delas administrou-se ração com cloreto de amônio e outras quatro receberam ração não suplementada com o produto. Avaliou-se o consumo de água, a produção de urina, os pH da urina e do sangue. Os resultados demonstraram que o ácido cítrico determinou diminuição do número de unidades formadoras de colônias, porém não interferiu no pH e densidade urinária dos animais. O cloreto de amônio reduziu o pH urinário demonstrando ação acidificante mesmo colhendo a urina 24 horas após o arraçoamento, porém não interferiu nas densidade e contagem bacteriana. Com relação o cloreto de sódio (1,5% ou 52,5 g/Kg de ração) não se observou qualquer efeito sobre os parâmetros estudados (pH urinário, densidade e contagem bacteriana). / The urinary infections(IU) in sows are among the main causes of reproductive imperfections that influence in the productivity of the flock, providing great economic damages. In the present work two acidifiers were tested out - acid citric and the chloride of ammonium and sodium chloride, in order to compare the activity of these products, in orther to control the cystitis in swine. 53 adult, pregnants and non pregnant sows were used , of tradeable ancestries, bearing, donþt bearing cystitis being identified the healthy or affected animals on the basis of the bacterial results of urinalysis culture. The first assay was carried out into two phases - phase 1 - carried through with 25 females in theirs early gestation (20 with cystitis and 5 healthy ones), fed gestation diet and phase 2 - carried through with 20 animals in gestation end (16 with cystitis and 4 healthy ones), fed with lactation ration. pH, the density and the number of CFUs in the urinary samples were the studied. As the assay 8 sows had been held envolving, all cystitis and not pregnant. Four out of 8 sows were fed with chrolide ammonium based rations. The remnants 4 were fed with no supplemented feed. The consumption of water, urinary output, urinary pH and the blood were also evaluated. The results showed that the citric acid determined a decrease in the CFU. However, it didnþt interfere at both pH and urinary density in the animals. The ammonium chloride reduced the urinary pH showing acidifying action even while collecting the urine after a period of 24 hours after the feeding time. Both density and CFU were not changed. Regarding the sodium chloride (1.5% or 52.5g/kg) nothing was found out within the complying parameters (pH urinary, dendity and CFU).