Targeting C-reactive protein for the treatment of cardiovascular disease

Complement-mediated inflammation exacerbates the tissue injury of ischaemic necrosis in heart attacks and strokes, the most common causes of death in developed countries. Large infarct size increases immediate morbidity and mortality and, in survivors of the acute event, larger non-functional scars adversely affect long-term prognosis. There is thus an important unmet medical need for new cardioprotective and neuroprotective treatments. We have previously shown that human C-reactive protein (CRP), the classical acute-phase protein that binds to ligands exposed in damaged tissue and then activates complement(1), increases myocardial and cerebral infarct size in rats subjected to coronary or cerebral artery ligation, respectively(2,3). Rat CRP does not activate rat complement, whereas human CRP activates both rat and human complement(4). Administration of human CRP to rats is thus an excellent model for the actions of endogenous human CRP2,3. Here we report the design, synthesis and efficacy of 1,6-bis(phosphocholine)-hexane as a specific small-molecule inhibitor of CRP. Five molecules of this palindromic compound are bound by two pentameric CRP molecules, crosslinking and occluding the ligand-binding B-face of CRP and blocking its functions. Administration of 1,6-bis(phosphocholine)-hexane to rats undergoing acute myocardial infarction abrogated the increase in infarct size and cardiac dysfunction produced by injection of human CRP. Therapeutic inhibition of CRP is thus a promising new approach to cardioprotection in acute myocardial infarction, and may also provide neuroprotection in stroke. Potential wider applications include other inflammatory, infective and tissue-damaging conditions characterized by increased CRP production, in which binding of CRP to exposed ligands in damaged cells may lead to complement-mediated exacerbation of tissue injury.

Fibroelastic Components of the Vesicourethral Junction of Rats in the Aging Process

The vesicourethral junction comprising the vesical trigone, is relevant in setting and positioning of the urinary bladder, along with the vesical neck, fixed by lateral ligaments of the bladder and tendinous arch of the pelvis fascia. Namely, the puboprostatic ligament (men) and the pubovesical (women). The circular set elastic fibers in this junction are important and valuable in the elasticity and plasticity of the area, allowing quick expansion and withdrawal with the flow of urine, and associated to smooth muscle tissue and nerve control form an important collective to maintain urinary continence. The objective of the present study is to describe the elastic system in the vesicouretral junction in relation to aging and its involvement in the states of urinary continence and incontinence, as well as the study of the vesicouretral junction in various age groups while evaluating with electron transmission microscopy. To carry out the study, 12 Wistar rats were used, divided into groups: neonate (4 animals), adult group (4 animals) and aged group (4 animals). Electron transmission microscopy with use of tanic acid technique associated to glutaraldehyde fixation, satisfactorily showed the extreme structural differences between mature elaunin and oxytalan fibers present between intercelular spaces and bundles of collagen fibers. The phases of elastogenesis in neonate animals and degradation of the elastic system of older animals were also evaluated.

Mäns upplevelser av miktionsproblem och erektil dysfunktion efter radikal prostatektomi : En litteraturöversikt

Syfte: Syftet var att beskriva hur män upplever att de påverkats av miktionsproblem och erektil dysfunktion efter radikal prostatektomi. Metod: Examensarbetet utfördes som en litteraturöversikt med tio vetenskapliga studier. Resultat: Upplevelsen av förlorad kontroll vid miktionsproblem var det som främst påverkade männen samt medförde att det sociala livet blev lidande. Männen beskrev hur de var tvungna att planera inför olika sociala tillställningar, vilket upplevdes som stressande och ångestfyllt. Det framkom också att männen oroade sig för urinläckage, stark odör och upplevde möten med oförstående människor som frustrerande. Erektil dysfunktion var den vanligaste komplikationen efter behandling, men miktionsproblem var det som orsakade mest besvär. Det upplevdes som att männen förlorat sin självständighet. Det framkom även att erektil dysfunktion upplevdes av vissa män som den komplikation som gav störst besvär. Erektil dysfunktion påverkade männen och var mycket svårt att hantera. Det var svårt att finna en acceptans för att den erektila dysfunktion kunde vara bestående. Många av männen beskrev att en viktig del i deras liv förlorats, en del av deras maskulinitet. De kände sig ofullständiga och det fanns en rädsla för att förlora sin partner. Slutsats: Studier visar att erektil dysfunktion och miktionsproblem i samband med radikal prostatektomi ger upphov till stress, oro, ångest samt en känsla av ofullständighet.

Protective effect of simvastatin in the cyclophosphamide-induced hemohrragic cystitis in rats

Cyclophosphamide (CYP) is an antineoplastic agent used for the treatment of many neoplastic and inflammatory diseases. Hemorrhagic cystitis is a frequent side effect of CYP. Several studies show that simvastatin has important pleiotropic (anti-inflammatory and immunomodulatory) effects. The purpose of the study was to investigate the effect of simvastatin on bladder, ureter and kidney injury caused by CYP. Methods: Adult male Wistar rats were randomly divided into three groups. The CYP/SIM group received simvastatin microemulsion by gavage during 7 days (10 mg/kg body wt) before the administration of CYP and the CYP/SAL group rats received saline 0.9%. The control rats were not treated. After that, all rats were treated with a single dose of CYP 200 mg/kg body wt intraperitoneally. The rats were killed 24 h after CYP administration. Plasma cytokines (TNF-a, IL-1b, IL-6) were measured by ELISA. Macro and light microscopic study was performed in the bladder, kidney and ureter. Results: In the bladders of CYP/SIMV treated rats edema of lamina propria with epithelial and sub-epithelial hemorrhage were lower than in CYP/SAL treated rats. The scores for macroscopic and microscopic evaluation of bladder and ureter were significantly lower in CYP/SIMV rats than in CYP/SAL rats. The kidney was not affected. The expression of TNF-a, IL-1b and IL-6 was significatly lower in CF/SINV rats (164.8±22, 44.8±8 and 52.4±13) than in CF/SAL rats (378.5±66, 122.9±26 e 123.6±18), respectively. Conclusion: The results of the current study suggest that simvastatin pretreatment attenuated CYP-induced urotelium inflammation and decreased the activities of cytokines

Influence of Splenectomy on the Biodistribution of Technetium-99m Dimercaptosuccinic Acid (99mTc-DMSA) in Rats

This study aimed to evaluate if the splenectomy alters the biodistribution of 99mTc-DMSA and renal function in Wistar rats. The animals were separated in the groups: splenectomy (n = 6) and control (n = 6). After splenectomy (15 days), the administration of 0.1ml of 99mTc-DMSA IV (0.48 MBq) was carried out. Thirty minutes later, kidney, heart, lung, thyroid, stomach, bladder and femur and samples of blood were isolated. The organs were weighed, counted and the percentage of radioactivity -g (%ATI-g) determined. Serum urea and creatinine, hematocrit, leukocytes and platelets were measured. Statistics by t test (p<0.05) was done. There was a significant reduction in %ATI-g in kidney and blood (p<0.05) of splenectomized animals, a significant increase (p<0.05) of urea (88.8 ± 18.6 mg-dL) and creatinine (0.56 ± 0.08 mg-dL), compared to the controls (51.5±1.6, 0.37±0.02mg-dL, respectively), as well as increase in platelets and leucocytes, and hematocrit reduction. The analysis of the results indicates that in rats, splenectomy seems to alter the renal function and the uptake of 99mTc-DMSA

Cuidados de enfermagem ao paciente em pós-operatório de prostatectomia: revisão integrativa

Este estudo trata-se de revisão integrativa da literatura com objetivo de sintetizar o conhecimento produzido em artigos sobre os cuidados de enfermagem aos pacientes em pós-operatório de prostatectomia. Para seleção dos artigos foram consultadas cinco bases de dados – SCOPUS, CINAHL, PUBMED, LILACS e Cochrane – sendo incluídos dezenove artigos. Os resultados mostram estudos que se enquadram nos níveis II, IV, V, VI e VII de evidência, a maioria realizada nos Estados Unidos durante os anos de 1999 a 2011. Os cuidados de enfermagem identificados foram agrupados em seis categorias: acompanhamento psicológico, orientações pós-operatórias, tratamento da disfunção erétil, tratamento da incontinência urinária, tratamento da dor e tratamento da hiponatremia. Conclui-se que os estudos com maior nível de evidência identificado recomendam cuidados de enfermagem centrados no acompanhamento psicológico, nas orientações do período pós-operatório e no tratamento da disfunção erétil. Destaca-se ainda que tais recomendações concentram-se, sobretudo, nas ações de apoio emocional e educativo

Detecção ultrassonográfica do ovário fetal em loba-guará (Chrysocyon brachyurus): relato de caso

Identificaram-se, por ultrassonografia, os ovários fetais e o sexo dos fetos em uma loba-guará. Ao exame ultrassonográfico, foi possível identificar estruturas fetais e realizar medidas (relação entre diâmetro cranial e abdominal dos fetos) que indicavam idade fetal de 59 dias. Observaram-se: estruturas torácicas e abdominais formadas, diafragma, membros, estruturas do crânio definidas, coluna vertebral, medula, costelas, batimentos cardíacos normais, movimentação fetal, câmaras e valvas cardíacas, grandes vasos, rins, peristaltismo intestinal e ovários fetais. O exame ultrassonográfico foi eficaz nessa espécie, pois foi possível observar estruturas fetais para a avaliação da viabilidade fetal e, também, identificou-se a imagem ovariana em um dos fetos, mostrando-se importante para estudos de sexagem fetal.

Diagnósticos de enfermagem em pacientes submetidos à hemodiálise: semelhanças entre o modelo de adaptação e a NANDA internacional

The nurses in the hemodialysis has an important role in the nursing process implementation, in the context of a theoretical referential. Among the nursing theories, highlights the Roy´s adaptations model, who considers a person as an holistic adaptive system that aims to adapt customers to different living conditions. Thus, it is believed that the Roy´s nursing process will guide nursing care to patients on dialysis. Therefore, the study aimed to analyze the nursing diagnosis present in patients with chronic kidney disease on hemodialysis based on the theoretical model of Roy and NANDA-International. Descriptive and cros-sectional study, performed at a dialysis center in a city in northeastern Brazil. Sample of 178 patients and consecutive sampling by convenience. Data collection ocurred from October/2011 until February/2012, through interview and physical examination forms. Data analysis was initiated by clinical reasoning, diagnosis judgment and similarity relation. Then, the data were entered into SPSS program, 16.0 version, generating descriptive statistics. The project was approved by the Ethics Research Committee (protocol nº 115/11) with a Presentation Certificate for Ethics Appreciation (in 0139.0.051.000-111) and was funded by the Universal edict MCT / CNPq 14/2010. The results revealed that most patients were male (52.2%), married (62.9%) and residents in the Natal´s metropolitan region (54.5%). The mean age was 46.6 years and the years of study, 8,5. Regarding nursing diagnosis obtained an average of 6.6, especially: Risk of Infection (100%), excessive fluid volume (99.4%) and hypothermia (61.8%). On the other hand the adaptive problems average was 6.4, and the most common: intracellular fluid retention (99.4%); Hyperkalemia (64.6%); Hypothermia (61.8%) and edema (53.9%). Were established 20 similarity relations between the NANDA-International nursing diagnosis and adaptive problems of Roy, namely: risk of falls / injury risk and potential for injury, impaired physical mobility and walking mobility and / or restricted coordination, dressing self-care deficit and loss of self-care ability; hypothermia and hypothermia; impaired skin integrity and impaired skin integrity; excessive fluid volume and intracellular fluid retention / Hyperkalemia / Hypocalcemia / edema; imbalanced nutrition: less than body requirements and Nutrition less than the body's needs; constipation and constipation, acute pain and acute pain, chronic pain and chronic pain, sensorial perception disturbed: visual, tactile and auditory disabilities and a primary sense: sight, hearing and tactile; sleep deprivation and insomnia, fatigue and intolerance to activities; ineffective self health and fails in the role; sexual dysfunction and sexual dysfunction; situational low self-esteem and low self-esteem, and diarrhea and diarrhea. We conclude that there is similarity between the typologies and was required a model´s analysis, because they present different ways to establish the nursing diagnosis. Moreover, the nursing process use, under the context of a theory and a classification system, subsidizes the care and contributes to the strengthening of nursing science

Critérios ecocardiográficos para definição de graus de disfunção ventricular em ratos portadores de estenose aórtica

OBJETIVO: O objetivo deste estudo foi identificar variáveis ecocardiográficas que definam graus de disfunção cardíaca em ratos com estenose aórtica (EAo). MÉTODOS: Ratos Wistar (n = 23), machos (90-100 g), foram submetidos a cirurgia para indução de EAo. As variáveis ecocardiográficas analisadas foram: diâmetros diastólico do ventrículo esquerdo (DDVE) e sistólico do átrio esquerdo em valores absolutos e normalizados para o peso corporal; diâmetro sistólico do VE (DSVE); três índices de encurtamento do VE (% de encurtamento endocárdico, %Enc.Endo; % de encurtamento miocárdico, %Enc.Mio; e velocidade de encurtamento da parede posterior do VE, VEPP); e índice de massa do VE (IMVE). Essas variáveis foram utilizadas para a análise de agrupamento (cluster analysis). RESULTADOS: A análise de agrupamento possibilitou separar os ratos com EAo em dois grupos: disfunção leve (n = 13) e disfunção severa (n = 9). Os intervalos de confiança das seguintes variáveis não apresentaram superposição dos seus valores: DDVE, DSVE, %Enc.Endo, %Enc.Mio, IMVE e VEPP. CONCLUSÃO: A utilização conjunta dos intervalos de confiança dessas variáveis permite identificar dois grupos de ratos com estenose aórtica e diferentes graus de comprometimento cardíaco, possibilitando a realização de estudos longitudinais com grupos homogêneos de animais.

Influence of rutin treatment on biochemical alterations in experimental diabetes

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Quality of life in women with vulvar cancer submitted to surgical treatment: a comparative study

Objectives: To investigate the occurrence and severity of lymphoedema of the lower extremities (LLE), quality of life (QoL), and urinary and sexual dysfunction in women with vulvar cancer submitted to surgical treatment.Study design: Twenty-eight patients with vulvar cancer submitted to vulvectomy and inguinofemoral lymphadenectomy and 28 healthy, age-matched women (control group) were evaluated. The occurrence and severity of LLE were determined by Miller's Clinical Evaluation. QoL, urinary function and sexual function were assessed by the EORTC QLQ-C30, SF-ICIQ and FSFI questionnaires, respectively. The differences between groups and correlations were assessed using Student's r-test, Chi-squared test, Mann-Whitney U-test and Spearman's rho test.Results: The groups were similar in terms of marital status, educational status, menopausal status, hormone therapy and height. The occurrence and severity of LLE were higher in women with vulvar cancer compared with the control group (p < 0.001 and p = 0.003, respectively). A significant association was found between the severity of LLE and advanced age (p = 0.04), and the severity of LLE and higher body mass index (BMI; p = 0.04) in patients with vulvar cancer. In the patients with vulvar cancer, there was a significant correlation between the severity of LLE and worse QoL in the following domains: physical, cognitive, emotional, social, fatigue, pain, sleep and financial questions (p < 0.05). There was no difference in urinary function between the two groups (p = 0.113). Age and number of deliveries were the only variables associated with the occurrence of urinary incontinence (p = 0.01). Urinary incontinence was present in women with a mean age of 74.9 +/- 4.6 years and a mean of 7.3 +/- 1.3 normal deliveries. There was no difference between the groups in terms of the sexual function. Multivariate analysis showed an association between sexual function and age (p = 0.01), and sexual function and being in a stable relationship (p = 0.02).Conclusion: Patients submitted to vulvectomy or inguinofemoral lymphadenectomy for vulvar cancer are at higher risk of developing LLE compared with healthy, age-matched women. This has a negative effect on QoL, but does not interfere with urinary or sexual function. (C) 2012 Elsevier B.V. All rights reserved.

Síndromes hipertensivas da gestação: identificação de casos graves

A hipertensão arterial está entre as causas mais freqüentes de morte materna. Entre os tipos presentes na gravidez destacam-se as manifestações específicas, isto é, a pré-eclâmpsia e a hipertensão gestacional, definidas clinicamente por aumento dos níveis da pressão arterial após a 20ª semana de gestação, associado (pré-eclâmpsia) ou não (hipertensão gestacional) à proteinúria. Na fase inicial a doença é assintomática, porém, quando não tratada ou não se interrompe a gestação, sua evolução natural é desenvolver as formas graves, como a eclâmpsia e a síndrome HELLP. Eclâmpsia é definida pela manifestação de uma ou mais crises convulsivas tônico-clônicas generalizadas e/ou coma, em gestante com hipertensão gestacional ou pré-eclâmpsia, na ausência de doenças neurológicas. Pode ocorrer durante a gestação, durante o trabalho de parto e no puerpério imediato. É comumente precedida pelos sinais e sintomas de eclâmpsia iminente (distúrbios do sistema nervoso central, visuais e gástricos). A associação de hemólise, plaquetopenia e disfunção hepática já era relatada na literatura na década de cinqüenta. em 1982, Weinstein reuniu estas alterações sob o acrônimo de HELLP, significando hemólise (H), aumento de enzimas hepáticas (EL) e plaquetopenia (LP), e denominou-as de síndrome HELLP. A literatura diverge em relação aos valores dos parâmetros que definem a síndrome. Sibai et al. (1986) propuseram sistematização dos padrões laboratoriais e bioquímicos para o diagnóstico da mesma, que foi adotada pelo Ministério da Saúde do Brasil. As manifestações clínicas podem ser imprecisas, sendo comuns queixas como dor epigástrica, mal-estar geral, inapetência, náuseas e vômitos. O diagnóstico precoce é, eminentemente, laboratorial e deve ser pesquisado de maneira sistemática nas mulheres com pré-eclâmpsia grave/eclâmpsia e/ou dor no quadrante superior direito do abdome. Diferenciar a síndrome HELLP de outras ocorrências, com manifestações clínicas e/ou laboratoriais semelhantes, não é tarefa fácil. O diagnóstico diferencial é particularmente difícil para doenças como púrpura trombocitopênica trombótica, síndrome hemolítico-urêmica e fígado gorduroso agudo da gravidez, devido à insuficiente história clínica e à semelhança dos aspectos fisiopatológicos. O conhecimento da fisiopatologia da pré-eclâmpsia, o diagnóstico precoce e a atuação precisa no momento adequado nas situações complicadas pela eclâmpsia e/ou síndrome HELLP permitem melhorar o prognóstico materno e perinatal.

Fraction of work-related accidents attributable to occupational noise in the city of Botucatu, São Paulo, Brazil

Background: Noise is the most common agent of occupational exposure. It may induce both auditory and extraauditory dysfunction and increase the risk of work accidents. The purpose of this study was to estimate the fraction of accidents attributable to noise occupational exposure in a mid-size city located in southeastern Brazil. Materials and Methods: In this population case-control study, which included 108 cases and 324 controls, the incidence rate ratio of work accidents controlled for several covariables was obtained by classifying occupational noise exposure into three levels, as well as determining the prevalence in each level. Results: Based on these data, the attributable fraction was estimated as 0.6391 (95 CI = 0.2341-0.3676), i.e., 63 of the work accidents that took place in the study site were statistically associated with occupational noise exposure. Discussion: The causes of this association as well as its implications in the prevention of work accidents are discussed.

Development of a rabbit's urethral sphincter deficiency animal model for anatomical-functional evaluation

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Avaliação do desempenho e de parâmetros gastrintestinais de frangos de corte alimentados com dietas formuladas com sorgo alto tanino e baixo tanino

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)