Cefepime distribution by microdialysis in peritoneal fluid of rats with or without experimental peritonitis.

The aim of this study was to investigate the penetration of cefepime into rat peritoneal fluid by microdialysis and to determine the relationship between unbound drug plasma and tissue concentration in healthy animals and in a sepsis model established through cecal ligation and puncture-induced peritonitis. Probe recovery was performed by dialysis and retrodialysis. Cefepime was administered at a dose of 110 mg/kg intravenously. Samples were collected for about 4 h, and concentrations were determined by liquid chromatography-electrospray ionization-QTOF MS. Tissue penetration was also determined. Probe recovery in vivo was 38.78% ± 3.31% and 38.83% ± 2.74% in the control and peritonitis groups, respectively. Cefepime was rapidly distributed in the peritoneal fluid in both groups. The peritoneal fluid/plasma cefepime ratio was 0.38 and 0.32 for the control and peritonitis groups, respectively. Cefepime concentrations were above the MIC of 4 mg/L for the main enterobacteria. The infection model that was used had no apparent effect on the pharmacokinetics of cefepime in rats. This was the first study to determine free cefepime concentrations in the peritoneal fluid of healthy rats and rats with experimental peritonitis.

Fast determination of free metronidazole in rat plasma and peritoneal fluid using HPLC-UV method.

Peritonitis refers to the inflammatory reaction of the peritoneum to aggression. In addition, it contributes significantly to sepsis. The presence of free concentrations of antimicrobials above the minimum inhibitory concentration at the site of infection is critical to therapeutic response. Metronidazole (MTZ) is an antimicrobial used to treat peritonitis because of its effectiveness against anaerobic microorganisms. This study investigates free MTZ concentrations in peritoneal microdialysate in Wistar rats. A C18 column (150 × 4.0 mm, 5 µm) was used for the analysis conducted at 40°C under isocratic conditions. The mobile phase consisted of acetonitrile and an aqueous solution of 50-mM monobasic phosphate buffer and 0.1% triethylamine, with pH 3.0 (10:90, v/v). MTZ calibration was linear in the range of 0.5-30.0 µg/ml. The intra- and inter-day precision was satisfactory with relative standard deviation ≤5.67%. The accuracy ranged from 90.64 to 103.77%, and the lower limit of quantification was 0.5 µg/ml. The developed method was successfully applied in a pilot pharmacokinetic study after MTZ administration (30 mg/kg, intravenously) in rats. The main advantage of the employed method is that it does not require sample processing and protein removal steps. This is the first study to be conducted using MTZ in rats.

Development and validation of an LC-ESI-QTOF-MS method to measure cefepime in the plasma and peritoneal fluid of rats using microdialysis: Application in a pilot pharmacokinetic study.

Cefepime (CEF) is a cephalosporin and can be administered in secondary peritonitis together with metronidazole to treat sepsis. This study aimed to develop and validate an LC-ESI-QTOF-MS method for the quantification of cefepime in the plasma and peritoneal microdialysate of healthy Wistar rats. Chromatographic separation was performed using a CLC-ODS C18 column (250 × 4.6 mm), a C18 pre-column (4 mm, 5 µm) and isocratic elution. Gallic acid was used as the internal standard. The mobile phase consisted of (A) ultrapure water (pH adjusted to 3.5) and (B) acetonitrile (80:20, v/v) at 0.8 ml/min. Quantification was performed using a mass spectrometer with electrospray ionization in positive mode to monitor ions with m/z 481.1322 (CEF) and m/z 171.0288 (IS). The method was validated for selectivity, precision, accuracy, linearity, stability, lower limit of quantification, carryover, recovery and matrix effect. Calibration was done in the ranges 1-40 and 1-100 µg/ml for the peritoneal microdialysate and plasma, respectively. Plasma extraction recovery ranged from 93.9 to 99.9%. The technique was validated and successfully applied in a pilot pharmacokinetic study for estimating the free concentration of CEF in the peritoneal microdialysate of rats for the first time.

Performance of creatinine-based equations for estimating glomerular filtration rate compared to endogenous creatinine clearance / Desempenho das equações baseadas em creatinina para estimativa da taxa de filtração glomerular comparadas à depuração da creatinina endógena

Abstract Introduction: The guidelines recommend estimating the glomerular filtration rate using serum creatinine-based equations as a predictor of kidney disease, preferably adjusted for local population groups. Methods: Cross-sectional study that evaluated the performance of four equations used for estimating GFR compared to endogenous creatinine clearance (ClCr) in 1,281 participants. Modification of Diet equations in Renal Disease Study Group (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), CKD-EPI with adjustment for local population (CKD-EPI local) and Full Age Spectrum (FAS) in comparison with endogenous creatinine clearance (ClCr). We used the Quantile Regression to calculate the median bias, interquartile range (IQR), Bland-Altman agreement analysis and 30% margin of error (P30). Results: The mean age of participants was 52.5 ± 16.5 years with 466 women (38%), median ClCr[IQR] of 92.0 [58.0; 122.0] mL/min/1.73 m2, with 320 (25%) participants presenting ClCr < 60 mL/min/1.73 m2. The performance of the local CKD-EPI and FAS equations were superior to MDRD and CKD-EPI in relation to variability (0.92 [0.89; 0.94]) and P30 (90.5% [88.7; 92, 0]). In the group with ClCr < 60 mL/min/1.73 m2, the local CKD-EPI and FAS equations showed less variability than the CKD-EPI and MDRD (0.90 [0.86; 0.98] and 1.05 [0.97; 1.09] vs. 0.63 [0.61; 0.68] and 0.65 [0.62; 0.70], P < 0.01) and best P30 (85.5) % [81.0; 90.0], 88.0% [84.0; 92.0] vs. 52.0% (46.0; 58.0) and 53.0% [47.0; 58 .5], P < 0.01). Conclusion: Local CKD-EPI and FAS equations performed better than CKD-EPI and MDRD when compared to ClCr.

Resumo Introdução: As diretrizes recomendam a estimativa da taxa de filtração glomerular pelo uso de equações baseadas em creatinina sérica como preditor de doença renal, preferencialmente ajustadas para grupos populacionais locais. Métodos: Estudo transversal que avaliou o desempenho de quatro equações para estimativa da TFG em comparação com a depuração de creatinina endógena (DCE) em 1.281 participantes. Foram avaliadas as equações Modification of Diet in Renal Disease Study Group (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), CKD-EPI com ajuste para a população local (CKD-EPI local) e Full Age Spectrum (FAS) em comparação com a depuração de creatinina endógena (DCE). Utilizamos a Regressão Quantílica para cálculo do viés mediano, intervalo interquartil (IQR), análise de concordância de Bland-Altman e margem de erro de 30% (P30). Resultados: A idade média dos participantes era de 52,5 ± 16,5 anos com 466 mulheres (38%), mediana da DCE [IQR] de 92,0 [58,0; 122,0] mL/min/1,73 m2, com 320 (25%) participantes apresentando DCE < 60 mL/min/1,73 m2. A performance das equações CKD-EPI local e FAS foram superiores às MDRD e CKD-EPI em relação à variabilidade (0,92 [0,89; 0,94]) e P30 (90,5% [88,7; 92,0]). No grupo com DCE < 60 mL/min/1,73 m2, as equações CKD-EPI local e FAS apresentaram menor variabilidade que as CKD-EPI e MDRD (0,90 [0,86; 0,98] e 1,05 [0,97; 1,09] vs. 0,63 [0,61; 0,68] e 0,65 [0,62; 0,70], P < 0,01) e melhores P30 (85,5% [81,0; 90,0], 88,0% [84,0; 92,0] vs. 52,0% (46,0; 58,0) e 53,0% [47,0; 58,5], P < 0,01). Conclusão: As equações CKD-EPI local e FAS tiveram desempenho superior às CKD-EPI e MDRD, quando comparadas a DCE.

Performance of creatinine-based equations for estimating glomerular filtration rate compared to endogenous creatinine clearance.

INTRODUCTION: The guidelines recommend estimating the glomerular filtration rate using serum creatinine-based equations as a predictor of kidney disease, preferably adjusted for local population groups. METHODS: Cross-sectional study that evaluated the performance of four equations used for estimating GFR compared to endogenous creatinine clearance (ClCr) in 1,281 participants. Modification of Diet equations in Renal Disease Study Group (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), CKD-EPI with adjustment for local population (CKD-EPI local) and Full Age Spectrum (FAS) in comparison with endogenous creatinine clearance (ClCr). We used the Quantile Regression to calculate the median bias, interquartile range (IQR), Bland-Altman agreement analysis and 30% margin of error (P30). RESULTS: The mean age of participants was 52.5 ± 16.5 years with 466 women (38%), median ClCr[IQR] of 92.0 [58.0; 122.0] mL/min/1.73 m2, with 320 (25%) participants presenting ClCr < 60 mL/min/1.73 m2. The performance of the local CKD-EPI and FAS equations were superior to MDRD and CKD-EPI in relation to variability (0.92 [0.89; 0.94]) and P30 (90.5% [88.7; 92, 0]). In the group with ClCr < 60 mL/min/1.73 m2, the local CKD-EPI and FAS equations showed less variability than the CKD-EPI and MDRD (0.90 [0.86; 0.98] and 1.05 [0.97; 1.09] vs. 0.63 [0.61; 0.68] and 0.65 [0.62; 0.70], P < 0.01) and best P30 (85.5) % [81.0; 90.0], 88.0% [84.0; 92.0] vs. 52.0% (46.0; 58.0) and 53.0% [47.0; 58 .5], P < 0.01). CONCLUSION: Local CKD-EPI and FAS equations performed better than CKD-EPI and MDRD when compared to ClCr.

Os biomarcadores ideais para o rastreamento de câncer de mama e de pulmão: uma revisão da literatura / The ideal markers for breast and lung cancer screening: a literature review

Os biomarcadores tumorais em sua maioria são proteínas ou pedaços de proteínas incluindo antígenos de superfície celular, proteínas citoplasmáticas, enzimas e hormônios. O objetivo desse trabalho e revisar quais são os biomarcadores ideais para o rastreamento de câncer de mama e do câncer de pulmão. A busca foi desenvolvida nos meses de fevereiro a março de 2020 através das seguintes bases de dados: Biblioteca Virtual em saúde (BVS), SciELO, PubMed, e o Google acadêmico. Ao todo foram encontrados 28 artigos, sendo artigos originais, revisões e resumos científicos. Os biomarcadores tumorais ideais para o rastreamento de câncer de mama são os receptores hormonais o estrógeno e a progesterona, Cerb B2, Catepsina D, e CA 15.3. Já os biomarcadores tumorais para o rastreamento do câncer de pulmão são os CEA (antígeno carcinoembrionário), TPA (antígeno polipeptídeo tecidual), SCC-Ag (antígeno de carcinoma de células escamosas), Chr A (cromogranina A) e o NSE (enolase neurônio-específica). Conclui-se mediante a realização da revisão bibliográfica, que o estudo dos biomarcadores tumorais tem se mostrado de grande importância no rastreamento do câncer de mama e de pulmão. São eles que orientam a conduta quanto ao prognóstico, grau de estadiamento, tratamento e posteriormente para acompanhar a sua eficácia.

Most tumor biomarkers are proteins or pieces of protein including cell surface antigens, cytoplasmic proteins, enzymes and hormones. The purpose of this work is to review what are the ideal biomarkers for screening for breast cancer and lung cancer. The search was developed from February to March 2020 through the following databases: Virtual Health Library (VHL), Scielo, Pubmed and Google Academic. In all, 28 articles were found, including original articles, reviews, scientific abstracts. The ideal tumor biomarkers for breast cancer screening are the hormone receptors estrogen and progesterone, Cerb B2, Cathepsin D, CA 15.3.The tumor biomarkers for lung cancer screening are CEA (carcinoembryonic antigen), TPA (tissue polypeptide antigen), SCC-Ag (squamous cell carcinoma antigen), Chr A (chromogranin A) and NSE (neuron enolase -specific). It is concluded that by carrying out this literature review, in which the study of tumor biomarkers has shown to be of great importance in screening for breast and lung cancer. They are the ones who guide the conduct regarding prognosis degree of staging, treatment and subsequently to monitor its effectiveness.

Interleukin-10 negatively modulates extracellular signal-regulated kinases 1 and 2 in aorta from hypertensive mouse induced by angiotensin II infusion.

The activation of extracellular signal-regulated kinase 1 and 2 (ERK 1/2) pathway promotes increased vascular contractility in angiotensin II (Ang II)-induced hypertensive mice. Interleukin-10 (IL-10) is an immune-regulatory cytokine with the ability to prevent vascular hypercontractility during hypertension. We hypothesized that IL-10 would downregulate vascular ERK 1/2 activation during Ang II-induced hypertension. Wild-type (WT) or IL-10 knockout (IL-10-/- ) mice received Ang II infusion (90 ηg.min) or vehicle (saline), via osmotic mini-pumps (0.25 µL/h for 14 days), whereas another WT group were infused with exogenous IL-10 (0.5 ηg/min, 14 days) simultaneously, or not, with Ang II. Aortic rings were mounted in a myograph, and concentration-response curves to phenylephrine were evaluated, in the presence or absence of ERK 1/2 inhibitor (PD98059, 10 µm, 40 min). Protein expression of vascular ERK 1/2 was determined by Western blot. Ang II infusion increased the maximal contractile response in both WT and IL-10-/- mice. Concomitant infusion of IL-10 and Ang II prevented hypercontractility in the vasculature. Exogenous IL-10 infusion prevented ERK 1/2 activation and hypercontractility, induced by Ang II. These findings suggest that IL-10 negatively modulates ERK 1/2 activation and prevents hypercontractility during Ang II-induced hypertension.

Knowledge of diabetes mellitus: does gender make a difference?

OBJECTIVE: Diabetes mellitus (DM) is a chronic disease considered an important public health problem. In recent years, its prevalence has been exponentially rising in many developing countries. Chronic complications of DM are important causes of morbidity and mortality among patients, which impair their health and quality of life. Knowledge on disease prevention, etiology, and management is essential to deal with parents, patients, and caregivers. The aim of this study was to evaluate the knowledge regarding DM in an adult population from a Middle-western Brazilian city. METHODS: This was a cross-sectional study covering 178 adults, aged 18-64 years, who answered a diabetes knowledge questionnaire. In order to identify the difference between groups, analysis of variance was used. RESULTS: Higher knowledge scores were found regarding the role of sugars on DM causality, diabetic foot care, and the effects of DM on patients (blindness, impaired wound healing, and male sexual dysfunction). However, lower scores were found amongst types of DM, hyperglycemic symptoms, and normal blood glucose levels. Females tended to achieve better knowledge scores than males. CONCLUSION: Women had better knowledge regarding types of DM, normal blood glucose values, and consequences of hyperglycemia revealed that diabetes education should be improved.

Sun exposure and sun protection habits among high-school adolescents in Porto Alegre, Brazil.

Adolescents constitute an important audience for photoprotection programs. Sun exposure and sun protection habits acquired during adolescence have a significant impact on skin cancer incidence. We administered a questionnaire to 724 students about ultraviolet radiation effects, opinions about tanning, total time of sun exposure per day, photoprotection and activities in the sun. About 90% were aware of the association between sun exposure and skin cancer, and mass media was the main source of information. However, the great majority believed that tanning improved their appearance, and that it was worth taking the risk. The most prevalent outdoor activity among boys was sports; girls preferred walks and sunbathing. Sun exposure was significantly longer in summer, when 90% of the students went to the beach. About 47% reported sunscreen use in summer and only 3% reported using sunscreen during winter. These results emphasize the need for the promotion of photoprotective habits in our population and the importance of engaging physicians and school teachers in developing campaigns directed at this issue to achieve effective, long-lasting results. Adolescents are aware of the effects of ultraviolet radiation on the skin but campaigns have not successfully changed their sun exposure habits.

Estudo eletrofisiológico das propriedades neuronais intrínsicas passivas de CAI em fatias hipocampais de ratos e tecido humano / Electrophysiological study of the intrinsic passive properties neurons of the CAI in slices hippocampal rats and hippocampal human tissue

O presente estudo tem como objetivo verificar a utilização de ratos como controle experimentais para estudos In vitro com tecido hipocampal humano. As fatias obtidas de hipocampo de ratos Wistar machos (espessura de 400 um) e amostras de tecido hipocampal humano (espessura 500um) removidos durante o procedimento cirúrgico para o tratamento de epilepsia de lobo temporal refratária ao tratamento medicamentoso. As fatias mantidas imersas numa cuba com solução de Ringer em temperatura ambiente continuamente oxigenadas e posteriormente transferidas para uma cãmara de interface para registro eletrofisiológico. Registros intracelulares foram obtidos a partir dos neurônios piramidais de CA1 de ratos controles (CR), epilépticos no modelo da pilocarpina (ER) e tecido hipocampal humanos (HHT). Foram avaliadas as propriedades passivas (potencial de membrana, resistência de entrada, constante de tempo) antes e depois da perfusão com o Ringer O-Mg2+. A análise entre CR (n: 40) e ER (n:22) não demonstrou diferenças significativas nas propriedades estudadas. Entre CR e HHT (n:30) não foram observadas diferenças significativas nas propriedades intrínsecas passivas. A análise entre ET e HHT não revelou diferença no potencial de membrana e resistência de entrada, porém a constante de tempo antes da perfusão com o Ringer O-Mg2+ apresentou diferença. Nossos achados sugerem que neurônios hipocampais de CAI de ratos são válidos como grupo controle para estudos experimentais com tecido hipocampal humano

Análise de fraturas supracondilianas do úmero em crianças / Analysis of supracondylares Fractures of the Humerus in Children

Os autores realizaram um levantamento retrospectivo dos atendimentos de crianças com fratura supracondiliana do úmero, com o objetivo de analisar as características deste tipo de fratura, e comparar com a literatura. Foram revistos fichas e prontuários de pacientes atendidos no serviço de Traumatologia e Ortopedia do Hospital São Lucas da PUCRS que preencheram todos os dados do levantamento: idade, raça, lado acometido, classificação da fratura, complicações e tratamento. Os resultados encontrados são de 63 pacientes numa população que variou de 1 ano a 11 anos de idade. Lesões em extensão e flexão ocorreram em 78,5 por cento e 10,5 por cento dos casos, respectivamente. Houve predomínio do sexo masculino (63,4 por cento) e da raça branca (95,2 por cento). O lado esquerdo foi o mais acometido, em 55,6 por cento dos casos. Foi realizado tratamento cirúrgico em 76 por cento e conservador em 24 por cento. Quanto a classificação de Gartland, encontrou-se 8 por cento do tipo I, 17,4 por cento do tipo II, e 74,6 por cento do tipo III. Observou-se ainda complicações nervosas em 6,35 por cento dos casos, enquanto complicações vasculares ocorreram em 3,2 por cento. Os resultados obtidos vão ao encontro dos dados descritos na literatura, constatando a importância desta patologia em crianças e a necessidade de conhecimento das características, classificação e manejo dessa patologia.