Bad bugs and beleaguered bladders: Interplay between uropathogenic Escherichia coli and innate host defenses

Strains of uropathogenic Escherichia coli (UPEC) are the causative agents in the vast majority of all urinary tract infections. Upon entering the urinary tract, UPEC strains face a formidable array of host defenses, including the flow of urine and a panoply of antimicrobial factors. To gain an initial foothold within the bladder, most UPEC strains encode filamentous surface adhesive organelles called type 1 pili that can mediate bacterial attachment to, and invasion of, bladder epithelial cells. Invasion provides UPEC with a protective environment in which bacteria can either replicate or persist in a quiescent state. Infection with type 1-piliated E. coli can trigger a number of host responses, including cytokine production, inflammation, and the exfoliation of infected bladder epithelial cells. Despite numerous host defenses and even antibiotic treatments that can effectively sterilize the urine, recent studies demonstrate that uropathogens can persist within the bladder tissue. These bacteria may serve as a reservoir for recurrent infections, a common problem affecting millions each year.

Type 1 fimbrial expression enhances Escherichia coli virulence for the urinary tract.

Type 1 fimbriae are adhesion organelles expressed by many Gram-negative bacteria. They facilitate adherence to mucosal surfaces and inflammatory cells in vitro, but their contribution to virulence has not been defined. This study presents evidence that type 1 fimbriae increase the virulence of Escherichia coli for the urinary tract by promoting bacterial persistence and enhancing the inflammatory response to infection. In a clinical study, we observed that disease severity was greater in children infected with E. coli O1:K1:H7 isolates expressing type 1 fimbriae than in those infected with type 1 negative isolates of the same serotype. The E. coli O1:K1:H7 isolates had the same electrophoretic type, were hemolysin-negative, expressed P fimbriae, and carried the fim DNA sequences. When tested in a mouse urinary tract infection model, the type 1-positive E. coli O1:K1:H7 isolates survived in higher numbers, and induced a greater neutrophil influx into the urine, than O1:K1:H7 type 1-negative isolates. To confirm a role of type 1 fimbriae, a fimH null mutant (CN1016) was constructed from an O1:K1:H7 type 1-positive parent. E. coli CN1016 had reduced survival and inflammatogenicity in the mouse urinary tract infection model. E. coli CN1016 reconstituted with type 1 fimbriae (E. coli CN1018) had restored virulence similar to that of the wild-type parent strain. These results show that type 1 fimbriae in the genetic background of a uropathogenic strain contribute to the pathogenesis of E. coli in the urinary tract.

G1 arrest and down-regulation of cyclin E/cyclin-dependent kinase 2 by the protein kinase inhibitor staurosporine are dependent on the retinoblastoma protein in the bladder carcinoma cell line 5637.

The protein kinase inhibitor staurosporine has been shown to induce G1 phase arrest in normal cells but not in most transformed cells. Staurosporine did not induce G1 phase arrest in the bladder carcinoma cell line 5637 that lacks a functional retinoblastoma protein (pRB-). However, when infected with a pRB-expressing retrovirus [Goodrich, D. W., Chen, Y., Scully, P. & Lee, W.-H. (1992) Cancer Res. 52, 1968-1973], these cells, now pRB+, were arrested by staurosporine in G1 phase. This arrest was accompanied by the accumulation of hypophosphorylated pRB. In both the pRB+ and pRB- cells, cyclin D1-associated kinase activities were reduced on staurosporine treatment. In contrast, cyclin-dependent kinase (CDK) 2 and cyclin E/CDK2 activities were inhibited only in pRB+ cells. Staurosporine treatment did not cause reductions in the protein levels of CDK4, cyclin D1, CDK2, or cyclin E. The CDK inhibitor proteins p21(Waf1/Cip1) and p27 (Kip1) levels increased in staurosporine-treated cells. Immunoprecipitation of CDK2, cyclin E, and p2l from staurosporine-treated pRB+ cells revealed a 2.5- to 3-fold higher ratio of p2l bound to CDK2 compared with staurosporine-treated pRB- cells. In pRB+ cells, p2l was preferentially associated with Thrl6O phosphorylated active CDK2. In pRB- cells, however, p2l was bound preferentially to the unphosphorylated, inactive form of CDK2 even though the phosphorylated form was abundant. This is the first evidence suggesting that G1 arrest by 4 nM staurosporine is dependent on a functional pRB protein. Cell cycle arrest at the pRB- dependent checkpoint may prevent activation of cyclin E/CDK2 by stabilizing its interaction with inhibitor proteins p2l and p27.

Desenvolvimento de video educativo para a aprendizagem do autocateterismo vesical intermitente

A bexiga neurogênica é uma disfunção vesical decorrente principalmente da lesão medular. O cateterismo vesical intermitente é o tratamento mais indicado na atualidade, deve ser realizado de 4 a 6 vezes ao dia, durante toda a vida, visando a proteção do trato urinário superior e a aquisição da continência urinária. Na reabilitação desses indivíduos, a autocateterização vesical é um desafio enfrentado na busca pela autonomia, privacidade, inserção social e participação. Os vídeos educativos são utilizados para o aprendizado do autocateterismo em vários países, por serem de fácil utilização e acesso via internet. Apesar disso, não existem vídeos realizados para o contexto brasileiro, levando em consideração os cateteres urinários e a técnica utilizada no Brasil. Este estudo teve como objetivo desenvolver e validar um vídeo educativo para a realização do autocateterismo vesical intermitente limpo. Trata-se de um estudo quantitativo, desenvolvido em duas fases: 1ª fase com a avaliação de vídeos educativos públicos direcionados para a aprendizagem do autocateterismo vesical intermitente com a técnica limpa; e 2ª Fase, com o desenvolvimento e validação de um vídeo educativo voltado para aprendizagem do autocateterismo. O levantamento dos vídeos utilizou um site de compartilhamento de vídeos utilizando o descritor \"autocateterismo\". Os vídeos foram avaliados por três juízes da área de saúde. O processo de desenvolvimento e validação do roteiro do vídeo educativo utilizou questionários previamente ratificados. Participaram dessas etapas, respectivamente, 18 e 17 juízes experts em reabilitação e/ou no ensino em saúde. O levantamento mostrou que apenas 3,5% (172) do total de vídeos disponíveis no site pesquisado eram voltados para o aprendizado do autocateterismo no contexto brasileiro. Seis vídeos eram específicos para o autocateterismo, dos quais quatro tinham informações desatualizadas ou incorretas, apenas dois atingiram a pontuação aceitável. Na validação do roteiro observou-se um predomínio de participantes do sexo feminino (94,44%), com idade de 30 a 60 anos, dos quais 72,22% possuíam mestrado e 50% atuavam há mais de cinco anos na área de reabilitação. O roteiro foi considerado validado com 96,29% das respostas dos juízes \"concordo\" ou \"concordo totalmente\" nas questões referentes ao quesito objetivo, 91,09% para quesito conteúdo, 98,12% em relação ao quesito relevância, 75% quanto ao quesito ambiente, 71,11% no quesito linguagem verbal e 92,70% referente à inclusão de tópicos. A produção do vídeo contou com uso de tecnologia 3D e apoio de uma equipe técnica especializada. No que se refere à validação do conteúdo do vídeo educativo, o conteúdo do vídeo foi considerado validado com 100% dos juízes que responderam \"concordo\" ou \"concordo totalmente\" nas questões referentes à funcionalidade, 86,27% referentes à usabilidade, 97,06% no quesito eficiência, 100% para técnica audiovisual, 94,11% quanto ao ambiente e 97,05% procedimento. O vídeo educativo foi avaliado positivamente tanto pela qualidade das informações quanto pela didática do ensino, mostrando a relevância da validação de materiais educativos. A expectativa é disseminar o vídeo educativo em diferentes centros de reabilitação e Universidades, visando propagar e tornar o conhecimento sobre a temática mais acessível à sociedade e aos profissionais de saúde, em especial os de reabilitação. Além de incentivar e embasar metodologicamente o desenvolvimento de outros vídeos educativos na área da saúde

Mathematical modelling of the lower urinary tract

The lower urinary tract is one of the most complex biological systems of the human body as it involved hydrodynamic properties of urine and muscle. Moreover, its complexity is increased to be managed by voluntary and involuntary neural systems. In this paper, a mathematical model of the lower urinary tract it is proposed as a preliminary study to better understand its functioning. Furthermore, another goal of that mathematical model proposal is to provide a basis for developing artificial control systems. Lower urinary tract is comprised of two interacting systems: the mechanical system and the neural regulator. The latter has the function of controlling the mechanical system to perform the voiding process. The results of the tests reproduce experimental data with high degree of accuracy. Also, these results indicate that simulations not only with healthy patients but also of patients with dysfunctions with neurological etiology present urodynamic curves very similar to those obtained in clinical studies.

Urinary Biomarkers Indicative of Apoptosis and Acute Kidney Injury in the Critically Ill.

BACKGROUND Apoptosis is a key mechanism involved in ischemic acute kidney injury (AKI), but its role in septic AKI is controversial. Biomarkers indicative of apoptosis could potentially detect developing AKI prior to its clinical diagnosis. METHODS As a part of the multicenter, observational FINNAKI study, we performed a pilot study among critically ill patients who developed AKI (n = 30) matched to critically ill patients without AKI (n = 30). We explored the urine and plasma levels of cytokeratin-18 neoepitope M30 (CK-18 M30), cell-free DNA, and heat shock protein 70 (HSP70) at intensive care unit (ICU) admission and 24h thereafter, before the clinical diagnosis of AKI defined by the Kidney Disease: Improving Global Outcomes -creatinine and urine output criteria. Furthermore, we performed a validation study in 197 consecutive patients in the FINNAKI cohort and analyzed the urine sample at ICU admission for CK-18 M30 levels. RESULTS In the pilot study, the urine or plasma levels of measured biomarkers at ICU admission, at 24h, or their maximum value did not differ significantly between AKI and non-AKI patients. Among 20 AKI patients without severe sepsis, the urine CK-18 M30 levels were significantly higher at 24h (median 116.0, IQR [32.3-233.0] U/L) than among those 20 patients who did not develop AKI (46.0 [0.0-54.0] U/L), P = 0.020. Neither urine cell-free DNA nor HSP70 levels significantly differed between AKI and non-AKI patients regardless of the presence of severe sepsis. In the validation study, urine CK-18 M30 level at ICU admission was not significantly higher among patients developing AKI compared to non-AKI patients regardless of the presence of severe sepsis or CKD. CONCLUSIONS Our findings do not support that apoptosis detected with CK-18 M30 level would be useful in assessing the development of AKI in the critically ill. Urine HSP or cell-free DNA levels did not differ between AKI and non-AKI patients.

Disquisition of the stone and gravel, the nature of their formation in the human body clearly explained, with diagnostics for distinguishing those from other diseases of the kidnies, bladder ... /

Mode of access: Internet.

A practical essay on diseases of the viscera : particulary those of the stomach and bowels, the liver, spleen and urinaty bladder, in which their nature, treatment and cure, are cleary pointed out and explained /

Mode of access: Internet.

A treatise on biliary concretions, or, stones in the gall-bladder and ducts /

Mode of access: Internet.

Lithotomy or a treatise of the extracting of the stone out of the bladder : wherein an account is given of the various instruments used, and the method observed in that curious, but difficult, part of chirurgery : illustrated with twenty copper plates /

Mode of access: Internet.

Proceedings : WHO Regional Symposium on Vesical Calculus Disease, sponsored by the World Health Organization, Bangkok, Thailand, January 1972 /

Item 507-A-25.

Text-book of diseases of the kidneys and urinary organs /

Mode of access: Internet.

Philosophical, medical, and experimental essays ... /

Contiene: I. On the state of the population in Manchester, and other adjacent places -- II. On the proportional mortality of the small pox and measles, in the several periods of life, and different seasons of the year; together with its comparative fatality to males and females -- III. On the different quantities of rain which fall, at different heights, over the same spot of ground -- IV. On the solution of stones of the urinary and of the gall bladder, by water impregnated with fixed air -- V. On the nature and composition of urinary calculi -- VI. On the internal regulation of hospitals -- VII. On the influence of fixed air on the colours and vegetation of plants -- VIII. On the action of different manures -- IX. On the properties of different absorbents -- X. Miscellaneous observations, cases, and inquiries.

The modern treatment of stone in the bladder by litholapaxy : a description of the operation and instruments, with cases illustrative of the difficulties and complications met with /

Mode of access: Internet.