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1.
Crit Care ; 27(1): 207, 2023 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-37254158

RESUMO

BACKGROUND: The relevance of current consensus threshold to define oliguria has been challenged by small observational studies. We aimed to determine the optimal threshold to define oliguria in critically-ill patients. METHODS: Cohort study including adult patients admitted within a multi-disciplinary intensive care unit between January 1st 2010 and June 15th 2020. Patients on chronic dialysis or who declined consent were excluded. We extracted hourly urinary output (UO) measurements along with patient's characteristics from electronic medical records and 90-day mortality from the Swiss national death registry. We randomly split our data into a training (80%) and a validation (20%) set. In the training set, we developed multivariable models to assess the relationship between 90-day mortality and the minimum average UO calculated over time windows of 3, 6, 12 and 24 h. Optimal thresholds were determined by visually identifying cut-off values for the minimum average UO below which predicted mortality increased substantially. We tested models' discrimination and calibration on the entire validation set as well as on a subset of patients with oliguria according to proposed thresholds. RESULTS: Among the 15,500 patients included in this analysis (training set: 12,440, validation set: 3110), 73.0% (95% CI [72.3-73.8]) presented an episode of oliguria as defined by consensus criteria (UO < 0.5 ml/kg/h for 6 h). Our models had excellent (AUC > 85% for all time windows) discrimination and calibration. The relationship between minimum average UO and predicted 90-day mortality was nonlinear with an inflexion point at 0.2 ml/kg/h for 3 and 6 h windows and 0.3 ml/kg/h for 12 and 24 h windows. Considering a threshold of < 0.2 ml/kg/h over 6 h, the proportion of patients with an episode of oliguria decreased substantially to 24.7% (95% CI [24.0-25.4]). Contrary to consensus definition, this threshold identified a population with a higher predicted 90-day mortality. CONCLUSIONS: The widely used cut-off for oliguria of 0.5 ml/kg/h over 6 h may be too conservative. A cut-off of 0.2 ml/kg/h over 3 or 6 h is supported by the data and should be considered in further definitions of oliguria.


Assuntos
Injúria Renal Aguda , Estado Terminal , Adulto , Humanos , Estudos de Coortes , Oligúria , Injúria Renal Aguda/epidemiologia , Unidades de Terapia Intensiva , Estudos Retrospectivos
2.
BMJ Open ; 13(3): e070240, 2023 03 27.
Artigo em Inglês | MEDLINE | ID: mdl-36972972

RESUMO

INTRODUCTION: Previous studies demonstrated that the implementation of the Kidney Disease Improving Global Outcomes (KDIGO) guideline-based bundle, consisting of different supportive measures in patients at high risk for acute kidney injury (AKI), might reduce rate and severity of AKI after surgery. However, the effects of the care bundle in broader population of patients undergoing surgery require confirmation. METHODS AND ANALYSIS: The BigpAK-2 trial is an international, randomised, controlled, multicentre trial. The trial aims to enrol 1302 patients undergoing major surgery who are subsequently admitted to the intensive care or high dependency unit and are at high-risk for postoperative AKI as identified by urinary biomarkers (tissue inhibitor of metalloproteinases 2*insulin like growth factor binding protein 7 (TIMP-2)*IGFBP7)). Eligible patients will be randomised to receive either standard of care (control) or a KDIGO-based AKI care bundle (intervention). The primary endpoint is the incidence of moderate or severe AKI (stage 2 or 3) within 72 hours after surgery, according to the KDIGO 2012 criteria. Secondary endpoints include adherence to the KDIGO care bundle, occurrence and severity of any stage of AKI, change in biomarker values during 12 hours after initial measurement of (TIMP-2)*(IGFBP7), number of free days of mechanical ventilation and vasopressors, need for renal replacement therapy (RRT), duration of RRT, renal recovery, 30-day and 60-day mortality, intensive care unit length-of-stay and hospital length-of-stay and major adverse kidney events. An add-on study will investigate blood and urine samples from recruited patients for immunological functions and kidney damage. ETHICS AND DISSEMINATION: The BigpAK-2 trial was approved by the Ethics Committee of the Medical Faculty of the University of Münster and subsequently by the corresponding Ethics Committee of the participating sites. A study amendment was approved subsequently. In the UK, the trial was adopted as an NIHR portfolio study. Results will be disseminated widely and published in peer-reviewed journals, presented at conferences and will guide patient care and further research. TRIAL REGISTRATION NUMBER: NCT04647396.


Assuntos
Injúria Renal Aguda , Inibidor Tecidual de Metaloproteinase-2 , Humanos , Inibidor Tecidual de Metaloproteinase-2/urina , Estudos Prospectivos , Biomarcadores , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/prevenção & controle , Terapia de Substituição Renal , Estudos Multicêntricos como Assunto
3.
J Nephrol ; 36(4): 1047-1058, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36729289

RESUMO

INTRODUCTION: Renal scintigraphy (RS) is occasionally performed to assess the risk of persistent renal failure (PRF) in patients with acute kidney disease (AKD). However, its diagnostic performance has never been assessed. METHODS: We identified all patients with AKD for whom RS was performed in our institution between 2010 and 2017. PRF was defined as persistently low (< 33% of baseline) estimated glomerular filtration rates (eGFR), 1 year after RS. Nuclear medicine specialists reviewed RS data and rated, for each patient, the likelihood of PRF ("PRF score"). We evaluated the performance to predict PRF (area under the ROC curve (AUC)) of RS-derived parameters such as renal accumulation index, accumulation slope, and new parameters derived from serial kidney activity counts. We tested the ability of those parameters to improve a clinical model including hypertension, diabetes, AKI severity and baseline eGFR. Finally, we conducted sensitivity analyses using alternate PRF definitions. RESULTS: Among 97 patients included, 57 (59%) fulfilled the criteria for PRF. The PRF score was able to predict PRF with an AUC of 0.63. Similarly, the accumulation index and accumulation slope respective AUCs were 0.64 and 0.63. None of these parameters were able to improve the performance of the clinical model. Among new parameters, the 3rd/2nd minute activity ratio and 3rd/2nd minute activity slope had fair diagnostic performance (AUC 0.72 and 0.74, respectively) and improved the performance of the clinical model. Results were confirmed in sensitivity analyses. CONCLUSION: Conventional renal scintigraphy can identify patients at high risk of PRF with a high specificity but a low sensitivity. New parameters, with comparable diagnostic abilities can be obtained within three minutes of injection.


Assuntos
Injúria Renal Aguda , Humanos , Injúria Renal Aguda/diagnóstico por imagem , Injúria Renal Aguda/etiologia , Rim/diagnóstico por imagem , Taxa de Filtração Glomerular , Doença Aguda , Cintilografia
4.
J Crit Care ; 72: 154146, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36116287

RESUMO

BACKGROUND: Bioimpedance vector analysis (BIVA) has been suggested as a valuable tool in assessing volume status in critically ill patients. However, its effectiveness in guiding fluid removal by continuous renal replacement therapy (CRRT) has not been evaluated. METHODS: In this randomized controlled trial, 65 critically ill patients receiving CRRT were allocated on a 1:1 ratio to have UF prescribed and adjusted using BIVA fluid assessment in the intervention group (32 patients) or conventional clinical parameters (33 patients). The primary outcome was the lean body mass (LBM) water content at CRRT discontinuation, and the secondary outcomes included the mortality rate, urinary output, the duration of ventilation support, and ICU stay. RESULTS: The study group was associated with a lower water content of LBM (80.7 ± 9.4 vs. 85.9 ± 10.4%; p < 0.05), and a higher mean UF-rate and urinary output (1.5 ± 0.8 vs. 1.2 ± 0.5 ml/kg/h and 0.9 ± 0.9 vs 0.5 ± 0.6 ml/kg/h, both: p < 0.05). The mortality rate, the length of ICU stay, and ventilation support duration were similar. CONCLUSION: BIVA guided UF prescription may be associated with a lower rate of fluid overload. Larger studies are required to evaluate its impact on patients' outcomes.


Assuntos
Injúria Renal Aguda , Terapia de Substituição Renal Contínua , Humanos , Estado Terminal/terapia , Impedância Elétrica , Unidades de Terapia Intensiva , Ultrafiltração , Estudos Prospectivos , Água , Terapia de Substituição Renal , Injúria Renal Aguda/terapia
5.
Nurs Crit Care ; 27(6): 796-803, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-34989068

RESUMO

BACKGROUND: Situation-Background-Assessment-Recommendation (SBAR) is a tool for structuring communication between healthcare professionals. SBAR reduces medical errors, however few studies have evaluated its quality in real practice. AIMS: To describe the quality of SBAR utilization by intensive care unit (ICU) nurses during phone conversations with physicians. To assess the influence of nurses' training, professional experience, and call circumstances on this quality. STUDY DESIGN: This observational study was conducted in the adult ICU of a university hospital in French speaking Switzerland. All consecutive telephone calls from nurses to physicians during a calendar month, were recorded. Those related to a change in patients' clinical status were selected and analysed. The quality of SBAR utilization was assessed using a pre-defined analysis grid. Scores ranged from 0 (worst quality) to 100% (best quality). Nurses' sociodemographics and training record were collected. Multiple regression was used to assess determinants of SBAR quality including nurses characteristics and level of training. RESULTS: We analysed 290 phone calls, made by 99 nurses. The median SBAR quality score was 41% (interquartile range [IQR] 33-48). Quality scores varied across the four items of SBAR: Situation 88% (81-94), Background 17% (6-27), Assessment 17% (0-33), and Recommendation 33% (17-40). Factors independently associated with higher SBAR quality were age (-0.66%, p = .002, 95% CI [-1.07; -0.25]), primary language other than French (-8.40%, p = .017, 95% CI [-15.29; -1.51]), lack of ICU expertise (-9.25%, p = .013, 95% CI [-16.5;1-1.99]), and SBAR training in pre-graduate nursing education (+11.53%, p = .028, 95% CI [1.27; 22.79]). CONCLUSIONS: The quality of SBAR utilization remains low in ICU clinical practice. Pre- and post-graduate training seem to improve its quality. RELEVANCE TO CLINICAL PRACTICE: Pre-graduate mandatory training associated with multiple repetitions could improve nurses' SBAR utilization. Training using the SBAR tool should be combined with the development of nursing skills in assessment and clinical judgment.


Assuntos
Unidades de Terapia Intensiva , Médicos , Adulto , Humanos , Comunicação , Erros Médicos , Suíça
6.
JAMA Netw Open ; 4(11): e2133094, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34735011

RESUMO

Importance: The current definition and staging of acute kidney injury (AKI) considers alterations in serum creatinine (sCr) level and urinary output (UO). However, the relevance of oliguria-based criteria is disputed. Objective: To determine the contribution of oliguria, as defined by the Kidney Disease: Improving Global Outcomes (KDIGO) criteria, to AKI diagnosis, severity assessment, and short- and long-term outcomes. Design, Setting, and Participants: This cohort study included adult patients admitted to a multidisciplinary intensive care unit from January 1, 2010, to June 15, 2020. Patients receiving long-term dialysis and those who declined consent were excluded. Daily sCr level and hourly UO measurements along with sociodemographic characteristics and severity scores were extracted from electronic medical records. Long-term mortality was assessed by cross-referencing the database with the Swiss national death registry. The onset and severity of AKI according to the KDIGO classification was determined using UO and sCr criteria separately, and their agreement was assessed. Main Outcomes and Measures: Using a multivariable model accounting for baseline characteristics, severity scores, and sCr stages, the association of UO criteria with 90-day mortality was evaluated. Sensitivity analyses were conducted to assess how missing sCr, body weight, and UO values, as well as different sCr baseline definitions and imputations methods, would affect the main results. Results: Among the 15 620 patients included in the study (10 330 men [66.1%] with a median age of 65 [IQR, 53-75] years, a median Simplified Acute Physiology Score II score of 40.0 [IQR, 30.0-53.0], and a median follow-up of 67.0 [IQR, 34.0-100.0] months), 12 143 (77.7%) fulfilled AKI criteria. Serum creatinine and UO criteria had poor agreement on AKI diagnosis and staging (Cohen weighted κ, 0.36; 95% CI, 0.35-0.37; P < .001). Compared with the isolated use of sCr criteria, consideration of UO criteria enabled identification of AKI in 5630 patients (36.0%). Those patients had a higher 90-day mortality than patients without AKI (724 of 5608 [12.9%] vs 288 of 3462 [8.3%]; P < .001). On multivariable analysis accounting for sCr stage, comorbidities, and illness severity, UO stages 2 and 3 were associated with a higher 90-day mortality (odds ratios, 2.4 [95% CI, 1.6-3.8; P < .001] and 6.2 [95% CI, 3.7-10.5; P < .001], respectively). These results remained significant in all sensitivity analyses. Conclusions and Relevance: The findings of this cohort study suggest that oliguria lasting more than 12 hours (KDIGO stage 2 or 3) has major AKI diagnostic implications and is associated with outcomes irrespective of sCr elevations.


Assuntos
Injúria Renal Aguda/complicações , Injúria Renal Aguda/diagnóstico , Estado Terminal , Oligúria/etiologia , Índice de Gravidade de Doença , Estudos de Coortes , Taxa de Filtração Glomerular , Humanos , Oligúria/diagnóstico , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo
7.
Crit Care ; 25(1): 318, 2021 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-34461974

RESUMO

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2021. Other selected articles can be found online at https://www.biomedcentral.com/collections/annualupdate2021 . Further information about the Annual Update in Intensive Care and Emergency Medicine is available from https://link.springer.com/bookseries/8901 .


Assuntos
Artérias/fisiopatologia , Dióxido de Carbono/análise , Veias/fisiopatologia , Humanos , Monitorização Fisiológica/instrumentação , Monitorização Fisiológica/métodos , Prognóstico
8.
Toxins (Basel) ; 13(6)2021 05 27.
Artigo em Inglês | MEDLINE | ID: mdl-34071776

RESUMO

It is now recognized that additional exposure to mycotoxins may occur through inhalation of contaminated dust at a workplace. The aim of this study was to characterize the multi-mycotoxin exposure of French grain elevator workers using biomonitoring and airborne measurements. Eighteen workers participated in the study. Personal airborne dust samples were analyzed for their mycotoxin concentrations. Workers provided multiple urine samples including pre-shift, post-shift and first morning urine samples or 24 h urine samples. Mycotoxin urinary biomarkers (aflatoxin B1, aflatoxin M1, ochratoxin A, ochratoxin α, deoxynivalenol, zearalenone, α-zearalenol, ß-zearalenol, fumonisin B1, HT-2 toxin and T-2 toxin) were measured using a liquid chromatography-high-resolution mass spectrometry method. Grain elevator workers were highly exposed to organic airborne dust (median 4.92 mg.m-3). DON, ZEN and FB1 were frequent contaminants in 54, 76 and 72% of air samples, respectively. The mycotoxin biomarkers quantified were DON (98%), ZEN (99%), α-ZEL (52%), ß-ZEL (33%), OTA (76%), T-2 (4%) and HT-2 (4%). DON elimination profiles showed highest concentrations in samples collected after the end of the work shift and the urinary DON concentrations were significantly higher in post-shift than in pre-shift-samples (9.9 and 22.1 µg/L, respectively). ZEN and its metabolites concentrations did not vary according to the sampling time. However, the levels of α-/ß-ZEL were consistent with an additional occupational exposure. These data provide valuable information on grain worker exposure to mycotoxins. They also highlight the usefulness of multi-mycotoxin methods in assessing external and internal exposures, which shed light on the extent and pathways of exposure occurring in occupational settings.


Assuntos
Poluentes Ocupacionais do Ar/análise , Monitoramento Biológico/métodos , Micotoxinas/análise , Exposição Ocupacional , Adulto , Biomarcadores/urina , Fumonisinas/análise , Humanos , Masculino , Pessoa de Meia-Idade , Ocratoxinas/análise , Zearalenona/análise
9.
BMC Nephrol ; 22(1): 101, 2021 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-33740897

RESUMO

BACKGROUND: Renal replacement therapy (RRT) in critically ill patients is associated with high morbidity and mortality. The appropriateness of RRT initiation is sometimes questioned in elderly patients. Therefore, we sought to evaluate the long-term mortality, dialysis dependence and quality of life (QOL) of elderly patients who survived critical illness requiring RRT. METHODS: This is a monocentric observational study including all patients > 55 yo who received RRT for acute kidney injury in our intensive care unit (ICU) between January 2015 and April 2018. At the time of the study (May 2019), we assessed if they were still alive by cross referencing our hospital database and the Swiss national death registry. We sent survivors written information and, subsequently, contacted them over the phone. We obtained their consent for participation, asked about their dialytic status and performed an EQ-5D survey with visual analog scale (VAS). Results were stratified according to their age at the time of ICU admission (G1: "55-65 yo"; G2: "> 65-75 yo" and G3: "> 75 yo"). QOL in G3 patients were compared to G1 and G2 and to predicted values. RESULTS: Among the 352 eligible patients, 171 died during the index hospital admission. After a median follow-up time of 32.7 months (IQR 19.8), a further 62 had died (median time to death for ICU survivors 5.0 (IQR 15.0) months. Hence, 119 (33.6%) patients were still alive at the time of the study. We successfully contacted 96 (80.7%) of them and 83 (69.7%) were included in the study (G1: 24, G2: 44 and G3: 15). Only 6 (7.2%) were RRT dependent. Patients in G3 had lower EQ-5D and VAS scores than those in G1 and G2 (p < 0.01). These scores were also significantly lower than predicted values (p < 0.05). CONCLUSIONS: RRT patients have a very high in-hospital and post discharge mortality. Among survivors, RRT dependency was low. Irrespective of baseline values, patients > 75 yo who survived ICU had a lower QOL than younger patients. It was lower than predicted according to age and sex. The appropriateness of RRT initiation in elderly patients should be discussed according to their pre-existing QOL and frailty.


Assuntos
Injúria Renal Aguda/mortalidade , Injúria Renal Aguda/terapia , Unidades de Terapia Intensiva , Qualidade de Vida , Diálise Renal , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
10.
Toxins (Basel) ; 13(1)2021 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-33450876

RESUMO

Investigating workplace exposure to mycotoxins is of the utmost importance in supporting the implementation of preventive measures for workers. The aim of this study was to provide tools for measuring mycotoxins in urine and airborne samples. A multi-class mycotoxin method was developed in urine for the determination of aflatoxin B1, aflatoxin M1, ochratoxin A, ochratoxin α, deoxynivalenol, zearalenone, α-zearalenol, ß-zearalenol, fumonisin B1, HT2-toxin and T2-toxin. Analysis was based on liquid chromatography-high resolution mass spectrometry. Sample pre-treatments included enzymatic digestion and an online or offline sample clean-up step. The method was validated according to the European Medicines Agency guidance procedures. In order to estimate external exposure, air samples collected with a CIP 10 (Capteur Individuel de Particules 10) personal dust sampler were analyzed for the quantification of up to ten mycotoxins, including aflatoxins, ochratoxin A, deoxynivalenol, zearalenone, fumonisin B1 and HT-2 toxin and T-2 toxin. The method was validated according to standards for workplace exposure to chemical and biological agents EN 482. Both methods, biomonitoring and airborne mycotoxin measurement, showed good analytical performances. They were successfully applied in a small pilot study to assess mycotoxin contamination in workers during cleaning of a grain elevator. We demonstrated that this approach was suitable for investigating occupational exposure to mycotoxins.


Assuntos
Poluentes Atmosféricos/análise , Monitoramento Biológico/métodos , Micotoxinas/análise , Exposição Ocupacional/análise , Urina/química , Cromatografia Líquida , Humanos , Exposição Ocupacional/prevenção & controle , Saúde Ocupacional , Projetos Piloto , Espectrometria de Massas por Ionização por Electrospray , Espectrometria de Massas em Tandem
12.
Blood Purif ; 49(5): 567-575, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32126564

RESUMO

INTRODUCTION: Regional citrate anticoagulation (RCA) is the recommended anticoagulation modality for continuous renal replacement therapy (CRRT). RCA was associated with a low rate of complications in randomized controlled trials. However, little is known about the type and rate of complications in real life. We sought to describe complications associated with RCA in comparison with those associated with heparin anticoagulation. METHODS: In our institution, RCA has been the default anticoagulation modality for CRRT in all patients without contraindications since 2013. We have retrospectively reviewed all consecutive patients who received CRRT between January and December 2016 in our institution. For each CRRT session, we have assessed circuit duration, administered dose, as well as therapy-associated complications. Those parameters were compared according to whether the circuit was run in continuous veno-venous hemodialysis (CVVHD) mode with RCA or continuous veno-venous hemofiltration (CVVH) mode with heparin anticoagulation. RESULTS: We analyzed 691 CRRT sessions in 121 patients. Of those 400 (57.9%) were performed in CVVHD-RCA mode and 291 (42.1%) in CVVH-Heparin Mode. Compared with -CVVH-Heparin mode, CVVHD-RCA mode was associated with a longer circuit lifespan (median duration 54.9 interquartile range [IQR 44.6] vs. 15.3 h [IQR 22.4], p < 0.0001). It was associated with a higher rate of metabolic acidosis 77 (20.2%) vs. 18 (7.2%), (p < 0.0001), alkalosis 186 (48.7%) vs. 43 (17.1%), (p= 0.0001), and hypocalcemia 96 (25.07%) vs. 26 events (10.79%), p < 0.0001. However, the majority of these alterations were of benign or moderate severity. Only one possible citrate intoxication was observed. CONCLUSIONS: CVVHD-RCA was associated with a much longer circuit life but an increased rate of minor metabolic complications, in particular acid-base derangements. Some of these complications might have been prevented by therapy adaptation. Medical and nursing staff education is of major importance in the implementation of an RCA protocol.


Assuntos
Anticoagulantes , Ácido Cítrico , Terapia de Substituição Renal Contínua , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Coagulação Sanguínea/efeitos dos fármacos , Ácido Cítrico/administração & dosagem , Ácido Cítrico/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
13.
Toxicol Lett ; 314: 133-141, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31325633

RESUMO

Hexavalent chromium (Cr(VI)) compounds are classified as carcinogenic to humans. Whereas chromium measurements in urine and plasma attest to the last few hours of total chromium exposure (all oxidation states of chromium), chromium in red blood cells (RBC) is attributable specifically to Cr(VI) exposure over the last few days. Before recommending Cr in RBC (CrIE) as a biological indicator of Cr(VI) exposure, in vivo studies must be undertaken to assess its reliability. The present study examines the kinetics of Cr(VI) in rat after a single intravenous dose of ammonium dichromate. Chromium levels were measured in plasma, red blood cells and urine. The decay of the chromium concentration in plasma is one-phase-like (with half-life time of 0.55 day) but still measurable two days post injection. The excretion of urinary chromium peaks between five and six hours after injection and shows large variations. Intra-erythrocyte chromium (CrIE) was very constant up to a minimum of 2 days and half-life time was estimated to 13.3 days. Finally, Cr(III) does not interfere with Cr(VI) incorporation in RBC. On the basis of our results, we conclude that, unlike urinary chromium, chromium levels in RBC are indicative of the amount of dichromate (Cr(VI)) in blood.


Assuntos
Carcinógenos Ambientais/administração & dosagem , Carcinógenos Ambientais/metabolismo , Cromo/administração & dosagem , Cromo/sangue , Eritrócitos/metabolismo , Administração Intravenosa , Animais , Biomarcadores/sangue , Biomarcadores/urina , Carga Corporal (Radioterapia) , Carcinógenos Ambientais/farmacocinética , Carcinógenos Ambientais/toxicidade , Cromo/farmacocinética , Cromo/toxicidade , Masculino , Modelos Biológicos , Oxirredução , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Especificidade da Espécie , Toxicocinética
14.
Int J Artif Organs ; 42(5): 258-262, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30819024

RESUMO

Panton-Valentine leucocidin producing methicillin-resistant Staphylococcus aureus infections are rare but associated with very high mortality rates. We report the case of a 14-year-old patient with Panton-Valentine leucocidin producing methicillin-resistant Staphylococcus aureus infection and Influenza B pneumonia requiring veno-arterial extra-corporeal membrane oxygenator for refractory shock. In the absence of response to conventional therapy, we have inserted a Cytosorb® cartridge within the extra-corporeal membrane oxygenator circuit. A spectacular decrease in vasopressor requirements followed. Since clindamycin, a key component of Panton-Valentine leucocidin producing methicillin-resistant Staphylococcus aureus treatment, might be removed by Cytosorb® hemoadsorption, we have performed serial plasma concentrations measurements of the drug. Based on these measurements, we were able to develop a pharmacokinetic model incorporating variable plasma clearance. Patient's exposure was estimated before, during and after Cytosorb® hemoadsorption. According to this model, Cytosorb® hemoadsorption did not seem to result in significant clindamycin removal. Cytosorb® hemoadsorption during Panton-Valentine leucocidin producing methicillin-resistant Staphylococcus aureus infection appears safe and feasible and no adaptation of clindamycin dosage seems necessary.


Assuntos
Clindamicina , Oxigenação por Membrana Extracorpórea/métodos , Hemoperfusão/métodos , Taxa de Depuração Metabólica , Desintoxicação por Sorção/métodos , Infecções Estafilocócicas , Adolescente , Antibacterianos/administração & dosagem , Antibacterianos/farmacocinética , Clindamicina/administração & dosagem , Clindamicina/farmacocinética , Exotoxinas/sangue , Humanos , Leucocidinas/sangue , Masculino , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Infecções Estafilocócicas/complicações , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/fisiopatologia , Infecções Estafilocócicas/terapia , Staphylococcus aureus/isolamento & purificação , Staphylococcus aureus/patogenicidade
16.
Toxicology ; 410: 116-124, 2018 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-30243954

RESUMO

The present study investigated the effects of maternal exposure to the widely used pyrethroid insecticides, permethrin and esfenvalerate, on fetal testicular steroidogenesis. Pregnant Sprague-Dawley rats were administered permethrin at doses of 1, 10, 50, or 100 mg/kg/day, or esfenvalerate at 0.1, 1, 7.5 or 15 mg/kg/day, by gavage, from gestation day (GD) 13 to 19. Testicular testosterone production and the expression of several key genes necessary for cholesterol and androgen synthesis and transport were assessed in GD 19 male fetuses. Dams treated with 100 mg/kg/day of permethrin or 15 mg/kg/day of esfenvalerate showed clinical signs of neurotoxicity. The highest dose of esfenvalerate also resulted in reduced maternal body weight gain throughout the treatment period. In the fetal testes, mRNA expressions of HMG-CoA synthase and reductase, SR-B1, StAR, P450scc, 3ßHSD, P450 17A1, and 17ßHSD were not affected by exposure to either pyrethroid. No significant change was observed in ex vivo testosterone production. In conclusion, in utero exposure to permethrin or esfenvalerate has no effect on the testosterone biosynthesis pathway in the fetal rat testis up to maternal toxic doses.


Assuntos
Inseticidas/toxicidade , Nitrilas/toxicidade , Permetrina/toxicidade , Piretrinas/toxicidade , Esteroides/biossíntese , Testículo/efeitos dos fármacos , Testículo/metabolismo , Animais , Peso Corporal , Relação Dose-Resposta a Droga , Feminino , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Hormônios Esteroides Gonadais/sangue , Masculino , Exposição Materna , Síndromes Neurotóxicas/metabolismo , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Ratos , Ratos Sprague-Dawley , Testículo/embriologia
17.
Toxicol Lett ; 283: 77-85, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29180288

RESUMO

Many employees in the aluminum industry are exposed to a range of aluminum compounds by inhalation, and the presence of ultrafine particles in the workplace has become a concern to occupational health professionals. Some metal salts and metal oxides have been shown to enter the brain through the olfactory route, bypassing the blood-brain barrier, but few studies have examined whether aluminum compounds also use this pathway. In this context, we sought to determine whether aluminum was found in rat olfactory bulbs and whether its transfer depended on physicochemical characteristics such as solubility and granulometry. Aluminum salts (chloride and fluoride) and various nanometric aluminum oxides (13nm, 20nm and 40-50nm) were administered to rats by intranasal instillation through one nostril (10µg Al/30µL for 10days). Olfactory bulbs (ipsilateral and contralateral relative to instilled nostril) were harvested and the aluminum content was determined by graphite furnace atomic absorption spectrometry after tissue mineralization. Some transfer of aluminum salts to the central nervous system via the olfactory route was observed, with the more soluble aluminum chloride being transferred at higher levels than aluminum fluoride. No cerebral translocation of any of the aluminas studied was detected.


Assuntos
Compostos de Alumínio/metabolismo , Compostos de Alumínio/toxicidade , Encéfalo/metabolismo , Condutos Olfatórios/metabolismo , Administração Intranasal , Algoritmos , Cloreto de Alumínio , Compostos de Alumínio/farmacocinética , Animais , Cloretos/metabolismo , Cloretos/farmacocinética , Cloretos/toxicidade , Fluoretos/metabolismo , Fluoretos/farmacocinética , Fluoretos/toxicidade , Masculino , Mucosa Nasal/patologia , Bulbo Olfatório/metabolismo , Ratos , Ratos Sprague-Dawley , Espectrofotometria Atômica
18.
Nanomaterials (Basel) ; 7(11)2017 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-29144410

RESUMO

Fluorescence imaging of biological systems down to the single-molecule level has generated many advances in cellular biology. For applications within intact tissue, single-walled carbon nanotubes (SWCNTs) are emerging as distinctive single-molecule nanoprobes, due to their near-infrared photoluminescence properties. For this, SWCNT surfaces must be coated using adequate molecular moieties. Yet, the choice of the suspension agent is critical since it influences both the chemical and emission properties of the SWCNTs within their environment. Here, we compare the most commonly used surface coatings for encapsulating photoluminescent SWCNTs in the context of bio-imaging applications. To be applied as single-molecule nanoprobes, encapsulated nanotubes should display low cytotoxicity, and minimal unspecific interactions with cells while still being highly luminescent so as to be imaged and tracked down to the single nanotube level for long periods of time. We tested the cell proliferation and cellular viability of each surface coating and evaluated the impact of the biocompatible surface coatings on nanotube photoluminescence brightness. Our study establishes that phospholipid-polyethylene glycol-coated carbon nanotube is the best current choice for single nanotube tracking experiments in live biological samples.

19.
Reprod Toxicol ; 72: 106-114, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28655647

RESUMO

Pregnant Sprague-Dawley rats were administered the insecticide α-cypermethrin at doses of 0.1, 1, 5, or 10mg/kg/day, or di-isobutyl phthalate (DIBP) at 250mg/kg/day, by gavage, from gestation day (GD) 13 to 19. Testicular testosterone production and the expression of several key genes related to cholesterol and androgen synthesis and transport were assessed in GD 19 male fetuses. Dams treated with 10mg/kg/day of α-cypermethrin showed clinical signs of neurotoxicity and reduced body weight gain. α-Cypermethrin had no significant effect on post-implantation loss, fetal weight, incidence of male fetuses per litter, or anogenital distance of the male fetuses. In the fetal testes, mRNA expressions of HMG-CoA synthase and reductase, SRB1, StAR, P450scc, 3ßHSD, P450 17A1, and 17ßHSD were not affected by exposure to α-cypermethrin. Testosterone production by the fetal testis was significantly reduced at 5 and 10mg/kg/day of α-cypermethrin, although to a much smaller extent than in DIBP-exposed fetuses.


Assuntos
Inseticidas/toxicidade , Piretrinas/toxicidade , Testículo/efeitos dos fármacos , Animais , Peso Corporal/efeitos dos fármacos , Dibutilftalato/análogos & derivados , Dibutilftalato/toxicidade , Feminino , Feto/efeitos dos fármacos , Feto/metabolismo , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Masculino , Troca Materno-Fetal , Gravidez , Ratos Sprague-Dawley , Testículo/embriologia , Testículo/metabolismo , Testosterona/metabolismo
20.
Toxicol Lett ; 255: 63-70, 2016 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-27178267

RESUMO

Chromium(VI) compounds are classified as carcinogenic to humans. Whereas chromium measurements in urine and whole blood (i.e., including plasma) are indicative of recent exposure, chromium in red blood cells (RBC) is attributable specifically to Cr(VI) exposure. Before recommending Cr in RBC as a biological indicator of Cr(VI) exposure, in-vitro studies must be undertaken to assess its reliability. The present study examines the relationship between the chromium added to a blood sample and that subsequently found in the RBC. After incubation of total blood with chromium, RBC were isolated, counted and their viability assessed. Direct analysis of chromium in RBC was conducted using Atomic Absorption Spectrometry. Hexavalent, but not trivalent Cr, was seen to accumulate in the RBC and we found a strong correlation between the Cr(VI) concentration added to a blood sample and the amount of Cr in RBC. This relationship appears to be independent of the chemical properties of the human blood samples (e.g., different blood donors or different reducing capacities). Even though in-vivo studies are still needed to integrate our understanding of Cr(VI) toxicokinetics, our findings reinforce the idea that a single determination of the chromium concentration in RBC would enable biomonitoring of critical cases of Cr(VI) exposure.


Assuntos
Cromo/sangue , Monitoramento Ambiental/métodos , Eritrócitos/metabolismo , Biomarcadores/sangue , Sobrevivência Celular/efeitos dos fármacos , Cromo/toxicidade , Eritrócitos/efeitos dos fármacos , Humanos , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Espectrofotometria Atômica , Temperatura , Fatores de Tempo
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