Effect of cyclooxygenase inhibitors on gentamicin-induced nephrotoxicity in rats

The frequent use of nonsteroidal anti-inflammatory drugs (NSAID) in combination with gentamicin poses the additional risk of nephrotoxic renal failure. Cyclooxygenase-1 (COX-1) is the main enzyme responsible for the synthesis of renal vasodilator prostaglandins, while COX-2 participates predominantly in the inflammatory process. Both are inhibited by non-selective NSAID such as indomethacin. Selective COX-2 inhibitors such as rofecoxib seem to have fewer renal side effects than non-selective inhibitors. The objective of the present study was to determine whether the combined use of rofecoxib and gentamicin can prevent the increased renal injury caused by gentamicin and indomethacin. Male Wistar rats (250-300 g) were treated with gentamicin (100 mg/kg body weight, ip, N = 7), indomethacin (5 mg/kg, orally, N = 7), rofecoxib (1.4 mg/kg, orally, N = 7), gentamicin + rofecoxib (100 and 1.4 mg/kg, respectively) or gentamicin + indomethacin (100 and 5 mg/kg, respectively, N = 8) for 5 days. Creatinine clearance and alpha-glutathione-S-transferase concentrations were used as markers of renal injury. Animals were anesthetized with ether and sacrificed for blood collection. The use of gentamicin plus indomethacin led to worsened renal function (0.199 ± 0.019 ml/min), as opposed to the absence of a nephrotoxic effect of rofecoxib when gentamicin plus rofexicob was used (0.242 ± 0.011 ml/min). These results indicate that COX-2-selective inhibitors can be used as an alternative treatment to conventional NSAID, especially in situations in which risk factors for nephrotoxicity are present.Universidade de São Paulo Escola de Enfermagem Laboratório ExperimentalUniversidade de São Paulo Faculdade de Medicina Laboratório de Investigação MédicaUniversidade Federal de São Paulo (UNIFESP) Departamento de Clínica Médica Divisão de NefrologiaUNIFESP, Depto. de Clínica Médica Divisão de NefrologiaSciEL

Post-traumatic stress disorder symptoms among professionals during humanitarian aid in Haiti after the earthquake in 2010

The scope of this article is to screen the symptoms of Post-Traumatic Stress Disorder (PTSD) among the professionals who provided humanitarian aid for the Haitian population after the 2010 earthquake. It involvess a cross-sectional study. The Impact of Event Scale - Revised (IES-R) was used for screening symptoms of PTSD. The participants included 32 Brazilians (mean age = 37.58 +/-7.01), 22 Americans (mean age =33.67 +/-8.03) and 12 Ecuadorians (mean age = 44.80 +/- 15.88). The professionals did not have PTSD symptoms. The relationship between prior experience variables in disaster situations and the total score of the IES-R (F (2) = 4.34, p = 0.017), as well as prior experience in disaster situations and the intrusion subscale (F (2) = 3.94, p = 0.024) were significant in linear regression models. The number of prior experiences was revealed as a significant predictor for the total score of IES (p < 0.05). The results showed that current experiences can be exacerbated by memories of prior experiences, increasing the likelihood of developing PTSD. Therefore the mental health care of the professionals should foster the early identification of prior experience risk factors, thereby not permitting voluntary initiative to transcend selective criteria and specific care.O artigo tem por objetivo rastrear sintomatologia de transtorno de estresse pós-traumático (TEPT) em profissionais que prestaram ajuda humanitária à população haitiana, após o terremoto de 2010. Estudo transversal. A sintomatologia de TEPT foi avaliada pela Escala Impacto do Evento - Revisada (IES-R). Os participantes foram 32 brasileiros (idade m = 37.58 +/- 7.01), 22 estadosunidenses (idade m = 33.67 +/- 8.03) e 12 equatorianos (idade m = 44.80 +/- 15.88) e não apresentaram sintomatologia de TEPT. A relação entre as variáveis experiência prévia em situação de desastre e escore total da IES-R [F(2) = 4.34, p = 0.017] bem como experiência prévia em situação de desastre e subescala intrusão [F(2) = 3.94, p = 0.024] foram significantes nos modelos de regressão linear. Experiência prévia se mostrou preditor significante para escore total da IES-R (p < 0,05). Os resultados demonstraram que vivências atuais podem ser potencializadas pelas memórias de experiências anteriores, aumentando a probabilidade de desenvolvimento de TEPT. Portanto, o cuidado com a saúde mental dos profissionais deve favorecer a precoce identificação do fator de risco experiência prévia, não permitindo que a iniciativa voluntária se sobreponha aos critérios seletivos e aos cuidados específicos.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de PsiquiatriaInstituto Israelita de Ensino e Pesquisa Albert EinsteinUniversidade Católica de SantosUNIFESP, EPM, Depto. de PsiquiatriaSciEL

Correlation between mass and volume of collected blood with positivity of blood cultures

Background The collection of blood cultures is an extremely important method in the management of patients with suspected infection. Microbiology laboratories should monitor blood culture collection. Methods Over an 8-month period we developed a prospective, observational study in an adult Intensive Care Unit (ICU). We correlated the mass contained in the blood vials with blood culture positivity and we also verified the relationship between the mass of blood and blood volume collected for the diagnosis of bloodstream infection (BSI), as well as we explored factors predicting positive blood cultures. Results We evaluated 345 patients with sepsis, severe sepsis or septic shock for whom blood culture bottles were collected for the diagnosis of BSI. Of the 55 patients with BSI, 40.0 % had peripheral blood culture collection only. BSIs were classified as nosocomial in 34.5 %. In the multivariate model, the blood culture mass (in grams) remained a significant predictor of positivity, with an odds ratio 1.01 (i.e., for each additional 1 mL of blood collected there was a 1 % increase in positivity; 95 % CI 1.01–1.02, p = 0.001; Nagelkerke R Square [R2] = 0.192). For blood volume collected, the adjusted odds ratio was estimated at 1.02 (95 % CI: 1.01–1.03, p \u3c 0.001; R2 = 0.199). For each set of collected blood cultures beyond one set, the adjusted odds ratio was estimated to be 1.27 (95 % CI: 1.14–1.41, p \u3c 0.001; R2 = 0.221). Conclusions Our study was a quality improvement project that showed that microbiology laboratories can use the weight of blood culture bottles to determine if appropriate volume has been collected to improve the diagnosis of BSI

Improving the diagnosis of meningitis due to enterovirus and herpes simplex virus I and II in a tertiary care hospital

Background Enterovirus and herpes simplex viruses are common causes of lymphocytic meningitis. The purpose of this study was to analyse the impact of the use molecular testing for Enteroviruses and Herpes simplex viruses I and II in all suspected cases of viral meningitis. Methods From November 18, 2008 to November 17, 2009 (phase II, intervention), all patients admitted with suspected viral meningitis (with pleocytosis) had a CSF sample tested using a nucleic acid amplification test (NAAT). Data collected during this period were compared to those from the previous one-year period, i.e. November 18, 2007 to November 17, 2008 (phase I, observational), when such tests were available but not routinely used. Results In total, 2,536 CSF samples were assessed, of which 1,264 were from phase I, and 1,272 from phase II. Of this total, a NAAT for Enterovirus was ordered in 123 cases during phase I (9.7% of the total phase I sample) and in 221 cases in phase II (17.4% of the total phase II sample). From these, Enterovirus was confirmed in 35 (28.5%, 35/123) patients during phase I and 71 (32.1%, 71/221) patients during phase II (p = 0.107). The rate of diagnosis of meningitis by HSV I and II did not differ between the groups (13 patients, 6.5% in phase I and 13, 4.7% in phase II) (p = 1.0), from 200 cases in phase I and 274 cases in phase II. Conclusions The number of cases diagnosed with enteroviral meningitis increased during the course of this study, leading us to believe that the strategy of performing NAAT for Enterovirus on every CSF sample with pleocytosis is fully justified

Serum soluble-Fas is a predictor of red blood cell transfusion in critically ill patients

OBJECTIVE: To investigate the relation between the need for red blood cell transfusion and serum levels of soluble-Fas, erythropoietin and inflammatory cytokines in critically ill patients with and without acute kidney injury. METHODS: We studied critically ill patients with acute kidney injury (n=30) and without acute kidney injury (n=13), end-stage renal disease patients on hemodialysis (n=25) and healthy subjects (n=21). Serum levels of soluble-Fas, erythropoietin, interleukin 6, interleukin 10, iron status, hemoglobin and hematocrit concentration were analyzed in all groups. The association between these variables in critically ill patients was investigated. RESULTS: Critically ill patients (acute kidney injury and non-acute kidney injury patients) had higher serum levels of erythropoietin than the other groups. Hemoglobin concentration was lower in the acute kidney injury patients than in other groups. Serum soluble-Fas levels were higher in acute kidney injury and end-stage renal disease patients. Critically ill patients requiring red blood cell transfusions had higher serum levels of soluble-Fas (5,906±2,047 and 1,920±1,060; p<0.001), interleukin 6 (518±537 and 255+502; p=0.02) and interleukin 10 (35.8±30.7 and 18.5±10.9; p=0.02), better iron status and higher mortality rates in the first 28 days in intensive care unit. Serum soluble-Fas levels were independently associated with the number of red blood cell units transfused (p=0.02). Serum soluble-Fas behaved as an independent predictor of the need for red blood cell transfusion in critically ill patients (p=0.01). CONCLUSIONS: Serum soluble-Fas level is an independent predictor of the need for red blood cell transfusion in critically ill patients with or without acute kidney injury. Further studies are warranted to reconfirm this finding.OBJETIVO: Investigar a relação entre a transfusão de hemácias e os níveis séricos de Fas solúvel, eritropoietina e citocinas inflamatórias em pacientes gravemente enfermos, com e sem insuficiência renal aguda. MÉTODOS: Os seguintes grupos foram estudados: pacientes gravemente enfermos com insuficiência renal aguda (n=30) e sem insuficiência renal aguda (n=13), pacientes portadores de doença renal crônica terminal em hemodiálise (n=25) e indivíduos saudáveis (n=21). Os níveis séricos de Fas solúvel, eritropoietina, interleucina 6, interleucina 10 e ferro, além da concentração de hemoglobina e de hematócrito, foram analisados em todos os grupos. A associação entre tais variáveis foram estudadas nos pacientes gravemente enfermos. RESULTADOS: Os níveis séricos de eritropoietina mostraram-se mais elevados nos pacientes gravemente enfermos do que nos dos demais grupos. Concentrações mais baixas de hemoglobina foram documentadas nos pacientes com insuficiência renal aguda em relação aos demais. Níveis séricos mais elevados de Fas solúvel foram observados nos pacientes com insuficiência renal aguda e doença renal crônica terminal. Pacientes gravemente enfermos transfundidos apresentaram níveis séricos mais elevados de Fas solúvel (5.906±2.047 e 1.920±1.060; p<0,001), interleucina 6 (518±537 e 255±502; p=0,02), interleucina 10 (35,8±30,7 e 18,5±10,9; p=0,02) e ferro, além de maior mortalidade em 28 dias. Os níveis séricos de Fas solúvel mostraram-se independentemente associados ao número de transfusões (p=0,02). O nível sérico de Fas solúvel foi um preditor independente da necessidade de transfusão de hemácias em pacientes gravemente enfermos (p=0,01). CONCLUSÃO: O nível sérico de Fas solúvel é um preditor independente da necessidade de transfusão de hemácias em pacientes gravemente enfermos, com ou sem insuficiência renal aguda. Mais estudos clínicos e laboratoriais são necessários para confirmar tal resultado.Universidade Federal de São Paulo (UNIFESP)Hospital Israelita Albert EinsteinUNIFESPSciEL

SeptiFast for diagnosis of sepsis in severely ill patients from a Brazilian hospital

Objective To test and validate a multiplex real-time polymerase chain reaction method for bloodstream infections, as well as to compare the results with conventional blood culture.Methods A total of 114 consecutive patients with clinical evidence of sepsis were submitted to blood culture and LightCycler™ SeptiFast tests.Results More positive specimens (23; 20.2%) were detected using the LightCycler™ SeptiFast than the blood culture (17; 14.9%), with an agreement of 86.8%. Discordant results were seen in four patients positive only to blood culture, ten positive only to LightCycler™ SeptiFast and one to different pathogens found by each test. Infections with microorganisms detected only using blood culture reassured the need to perform both tests. The mean time to results for blood culture was 5 days for negative and 3.5 days for positive results. LightCycler™ SeptiFast results were achieved in less than 8 hours.Conclusion LightCycler™ SeptiFast showed a high potential as a test to be carried out concomitantly with blood culture for sepsis diagnosis in severely ill patients. This test allowed a faster diagnosis of bacterial and fungal infections that helped to reduce hospital stay and to control the use of antibiotics. LightCycler™ SeptiFast can also eventually detect microorganism and infections that are hardly detected by blood culture, especiallyCandidanon-albicans infections.</jats:p

Contribuição ao estudo do sistema renina angiotensina, calicreina cinina e hormônio antidiurético na síndrome hepatorenal em ratos

BV UNIFESP: Teses e dissertaçõe

Participação do fator ativador de plaquetas em alguns modelos de nefrotoxicidade, em ratos.

BV UNIFESP: Teses e dissertaçõe

Cellular and molecular aspects of nephrogenese

A ramificacao/tubulogenese do broto ureteral e fundamental para o desenvolvimento renal. O sistema de cultura de celulas em gel de tres dimensoes tem trazido grandes avancos ao entendimento dos mecanismos envolvidos na arborizacao. Nesta tese procura-se unificar estes achados com os obtidos atraves de tecnicas geneticas e de cultura de orgaos. Os dados sugerem a existencia de um balanco entre fatores facilitadores da tubulogenese, como o fator de crescimento hepatico (HGF) e componentes da matriz extracelular (MEC), como laminina, entactina e flbronectina, e fatores inibidores de crescimento, como o fator de crescimento transformador beta (TGF-b) e outras proteinas da MEC (vitronectina, colageno IV e heparan sulfato). Possivelmente, fatores distais ao acoplamento entre os ligantes (fatores de crescimento) e seus receptores (frequemtemente tirosina-quinase, PTK) agem como reguladores desta arborizacao. Assim, multiplas vias de fosforilacao mediadas por proteinas quinases (PKC, PKA e PTK), proteases extracelulares e intracelulares (especialmente as catepsinas), seus inibidores e integrinas, modulam a morfogenese do tubulo renal. Sao discutidos os aspectos relevantes deste conjunto de instrumentos celulares, abrindo a oportunidade de, na medida em que se conheca os mecanismos de diferenciacao/formacao, aplica-los futuramente na compreensao de alguns estados flsiopatologicos, como a doenca cistica renal e a regeneracao apos um insulto isquemicoBV UNIFESP: Teses e dissertaçõe