Níveis séricos de vitamina D e urinários de KIM-1 e MCP-1 em pacientes com anemia falciforme / Serum levels of vitamin D, and urinary levels of KIM-1 and MCP-1 in patients with sickle cell anemia

Objetivo: realizar dosagens de biomarcadores de função renal não convencionais em pacientes com anemia falciforme e associar com os níveis séricos de vitamina D. Métodos: trata-se de um estudo observacional, analítico de corte transversal. Participaram do estudo 51 pacientes adultos com anemia falciforme, e o grupo controle foi composto por 17 adultos saudáveis doadores de sangue. Os níveis séricos de 25- hidroxi-vitamina D foram determinados por imunoensaio quimioluminecente de micropartículas (CMIA), e a função renal foi avaliada pelas dosagens de molécula-1 de lesão renal (KIM-1) e proteína-1 quimiotática de monócitos (MCP-1). Os resultados foram expressos como mediana (intervalo interquartil). Os testes t-Student de amostras independentes, análise de variância de Welch e teste não paramétrico de Kruskal-Wallis foram realizados para comparar as diferenças entre os grupos. Resultados: os pacientes apresentaram níveis séricos de vitamina D superiores ao grupo controle, além de uma maior prevalência de suficiência de vitamina D. Os níveis urinários de KIM-1 e MCP-1 estavam aumentados nos pacientes em relação ao grupo controle. Não houve relação entre baixos níveis séricos de vitamina D e a probabilidade de desenvolvimento de doença renal. Conclusões: este estudo fornece dados importantes sobre a prevalência da deficiência de vitamina D em pacientes com anemia falciforme e demonstra não haver relação entre baixos níveis de vitamina D e desenvolvimento de doença renal.

Objective: to measure non-conventional renal function biomarkers in patients with sickle cell anemia and associate them with serum levels of vitamin D. Method: this is an observational, analytical, cross-sectional study. Fifty-one adult patients with sickle cell anemia participated in the study, and the control group consisted of 17 healthy adult blood donors. Serum levels of 25-hydroxyvitamin D were determined by chemiluminescent microparticle immunoassay (CMIA), and renal function was assessed by measuring urinary Kidney Injury Molecule-1 (KIM-1) and Monocyte Chemoattractant Protein-1 (MCP-1). Results were expressed as median (interquartile range). Student's t-test, Welch analysis of variance, and non-parametric Kruskal-Wallis test were performed to compare differences between groups. Results: patients had higher serum levels of vitamin D than the control group, besides a higher prevalence of vitamin D sufficiency. Urinary levels of KIM-1 and MCP-1 were increased in patients compared to the control group. There was no relationship between low serum vitamin D levels and the likelihood of developing kidney disease. Conclusions: this study provides important data on the prevalence of vitamin D deficiency in patients with sickle cell anemia and demonstrates that there is no relationship between low levels of vitamin D and the development of kidney disease.

Nephroprotective effects of Lippia sidoides ethanolic extract against ischemia/reperfusion-induced acute kidney injury

Abstract Ischemia/reperfusion injury (I/R) is commonly related to acute kidney injury (AKI) and oxidative stress. Antioxidant agents are used to treat this condition. Lippia sidoides is a brazillian shrub with anti-inflammatory and anti-oxidative properties. Thus, the aim of this study is to evaluate the effect of Lippia sidoides ethanolic extract (LSEE) on in vivo and in vitro models of AKI induced by I/R. Male Wistar rats were submitted to unilateral nephrectomy and ischemia on contralateral kidney for 60 min via clamping followed by reperfusion for 48 h. They were divided into four groups: Sham, LSEE (sham-operated rats pre-treated with LSEE), I/R (rats submitted to ischemia) and I/R-LSEE (rats treated with LSEE before ischemia). Kidney tissues homogenates were used to determine stress parameters and nephrin expression. Plasma and urine samples were collected for biochemical analysis. I/R in vitro assays were evaluated by 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) and flow cytometry assays in Rhesus Monkey Kidney Epithelial Cells (LLC-MK2). The LSEE treatment prevented biochemical and nephrin expression alterations, as well as oxidative stress parameters. In the in vitro assay, LSEE protected against cell death, reduced the reactive oxygen species and increased mitochondrial transmembrane potential. LSEE showed biotechnological potential for a new phytomedicine as a nephroprotective agent.

Association of serum lipoproteins and inflammatory parameters derived from the blood test with renal function in COVID-19 outpatients

Abstract Changes in lipoprotein metabolism are among the main causes of hemodynamic impairment in renal function. COVID-19 is an multisystemic inflammatory disease, aggravating this situation. This cross-sectional study investigated the relationship of serum lipoprotein profile with inflammatory parameters and renal function in 95 COVID-19 outpatients in comparison with 173 with flu-like symptoms. Serum samples were collected for the determination of total cholesterol and fractions, apolipoproteins (Apo A-I and Apo B), urea (sUr) and creatinine (sCr). The glomerular filtration rate (eGFR) was calculated. Neutrophil/lymphocyte (NLR) and platelet/lymphocyte (PLR) ratios were calculated as inflammatory parameters derived from the blood tests. COVID-19 patients presented lower high-density lipoprotein cholesterol (HDL-c) (47.90 ± 1.543 vs. 51.40 ± 0.992) and higher PLR (190.9 ± 9.410 vs. 137.6 ± 5.534) and NLR (3.40 ± 0.22 vs. 2.80 ± 0.15). Both NLR and PLR correlated with each other (r = 0.639). Furthermore, the Apo B/Apo A-I ratio was correlated with PLR (r = 0.5818) and eGFR (r = -0.2630). COVID-19 patients classified as at high risk of developing acute myocardial infarction based on the Apo B/ Apo A-I ratio had higher values for sUr/sCr. Thus, serum apolipoproteins, PLR, and NLR could be related to renal dysfunction in COVID-19.

Hypertriglyceridemia promotes dysfunctions in high-density lipoprotein increasing the cardiovascular risk

Abstract Hypertriglyceridemia is associated with several metabolic diseases. The triglycerides (TG) disrupt the cholesterol reverse transport and contribute to increased levels of low-density lipoprotein (LDL). High-density lipoprotein (HDL) acts in cholesterol reverse transport as an anti-inflammatory and antioxidant. This study aims to investigate the role of hypertriglyceridemia in the functionality of HDL. Individuals were divided into 4 groups based on high or low HDL-c and triglycerides levels. Biochemical and anthropometric analysis were performed. This study demonstrated that triglycerides promote dysfunctions on HDL, increasing the cardiovascular risk. Blood pressure was higher in subjects with low HDL. Women presented higher levels of HDL-c and low percentage of fat mass. The highest levels of triglycerides were observed in older age. In addition, high levels of triglycerides were associated with higher total cholesterol and LDL-c levels, non-HDL-c, non-esterified fatty acids, and blood glucose, increasing in the ratio of non-HDL-c/HDL-c and ApoB/ApoA-I. The increase of triglycerides levels progressively impairs the antioxidant capacity of HDL, probably due to a higher occurrence of fatty acid peroxidation in individuals with hypertriglyceridemia. Patients with high HDL and low TG levels increased the Lag Time. Furthermore, a positive correlation was found between TG versus HDL particle size, variables that depend on age and anthropometric parameters.

Tyramine exerts hypolipidemic and anti-obesity effects in vivo

Abstract Obesity and dyslipidemia are conditions often associated with cardiovascular risk, inflammation, oxidative stress, and death. Thus, a new approach has been highlighted to promote research and development of pharmacological tools derived from natural sources. Among the most widely studied groups of substances, polyphenols such as tyramine stand out. This study investigated hypolipidemic and anti-obesity properties of tyramine. Oral toxicity evaluation, models of dyslipidemia and obesity were used. To induce dyslipidemia, Poloxamer-407 (P-407) was administered intraperitoneally. In the hypercholesterolemic and obesity model, specific diet and oral tyramine were provided. After 24h of P-407 administration, tyramine 2 mg/kg (T2) decreased triglycerides (TG) (2057.0 ± 158.5 mg/dL vs. 2838 ± 168.3 mg/dL). After 48h, TG were decreased by T2 (453.0 ± 35.47 vs. 760.2 ± 41.86 mg/dL) and 4 mg/kg (T4) (605.8 ± 26.61 760.2 ± 41.86 mg/dL). T2 reduced total cholesterol (TC) after 24h (309.0 ± 11.17 mg/dL vs. 399.7 ± 15.7 mg/dL); After 48h, 1 mg/kg (T1) (220.5 ± 12.78 mg/dL), T2 (205.8 ± 7.1 mg/dL) and T4 (216.8 ± 12.79 mg/dL), compared to P-407 (275.5 ± 12.1 mg/dL). The treatment decreased thiobarbituric acid reactive substances and nitrite in liver, increased superoxide dismutase, reduced the diet-induced dyslipidemia, decreasing TC around 15%. Tyramine reduced body mass, glucose, and TC after hypercaloric feed. Treatment with 5 mg/L (0.46 ± 0.04 ng/dL) and 10 mg/L (0.44 ± 0.02 ng/dL) reduced plasma insulin (1.18 ± 0.23 ng/dL). Tyramine increased adiponectin at 5 mg/L (1.02 ± 0.02 vs. 0.83 ± 0.02 ng/mL) and 10mg/L (0.96 ± 0.04 ng/mL). In conclusion, tyramine has low toxicity in rodents, has antioxidant effect, reduces plasma triglycerides and cholesterol levels. However, further studies should be conducted in rodents and non-rodents to better understand the pharmacodynamic and pharmacokinetic properties of tyramine

Linfoma de Hodgkin em Pacientes HIV Positivo em Uso de Antirretrovirais de Alta Efetividade / Hodgkin Lymphoma in HIV Positive Patients in The Use of High-Effective Antiretroviral / Linfoma de Hodgkin en Pacientes VIH Positivos en el Uso de Antiretrovirales de Alta Efectividad

Introdução: A capacidade do vírus da imunodeficiência humana (HIV) de invadir células do sistema imunológico, principalmente células T CD4+, para se multiplicar e manter-se vivo, quando não revertido, possui, como desfecho inevitável, a síndrome da imunodeficiência adquirida (SIDA), evento no qual os pacientes começam a apresentar doenças secundárias como infecções oportunistas e câncer. Objetivo:Identificar casos de linfoma de Hodgkin em pacientes HIV+ em uso dos antirretrovirais de alta efetividade. Método: Estudo do tipo observacional transversal com delineamento exploratório e descritivo e abordagem quali-quantitativa, realizado durante o mês de outubro de 2018, a partir da análise de 57prontuários de pacientes HIV+ diagnosticados com câncer e internados em um hospital localizado em Fortaleza, CE. Resultados: Foi identificado um total de 21 cânceres não definidores de SIDA. Destes, os mais comuns foram o câncer de pele com 14,3% (3); seguido do câncer de mama com 9,5% (2); linfoma de Hodgkin com 9,5% (2); e o câncer de estômago com 9,5% (2) dos casos. Conclusão: Os dados obtidos no presente estudo colocam o linfoma de Hodgkin em segundo lugar entre os cânceres não definidores de SIDA encontrados. Contudo, ao considerar o baixo número de casos, resultante das limitações da pesquisa, essas informações não permitem concluir sobre a real quantidade de linfomas de Hodgkin entre os demais cânceres não definidores de SIDA ocorridos em pacientes HIV+ na localidade, tampouco estimar a participação do HIV, carga viral, condição imunológica e coinfecções como fatores de risco.

Introduction: The ability of the human immunodeficiency virus (HIV) of invading immune system cells, especially CD4+ to multiply and stay alive, when not reversed, has as inevitable outcome the acquired immunodeficiency syndrome (AIDS), an event in which patients start to develop secondary diseases such as opportunistic infections and cancer. Objective: To identify cases of Hodgkin's lymphoma in HIV+ patients using highly effective antiretrovirals. Method: Cross-sectional observational study with exploratory and descriptive design and qualitative and quantitative approach, carried out during the month of October 2018 based on the analysis of 57 HIV-infected patients' charts diagnosed with cancer and admitted to a hospital located in Fortaleza, CE. Results: A total of 21 non-AIDS-defining cancers were detected. Of these, skin cancer, with 14.3% (3) followed by breast cancer, with 9.5% (2), Hodgkin's lymphoma, 9.5% (2) and stomach cancer, with 9.5% (2) were the most common cases. Conclusion: The data obtained in the present study rank Hodgkin's lymphoma in second place among the non-AIDS-defining cancers encountered. However, while considering the small number of cases, due to the study limitations, these data are scanty to conclude the actual quantity of Hodgkin's lymphoma among the non-AIDS-defining cancers occurred in HIV-positive patients locally or to estimate the participation of HIV, viral load, immune condition and co-infection as risk factors.

Introducción: La capacidad del virus de inmunodeficiencia humana (VIH) para invadir las células del sistema inmunitario, especialmente las células T CD4 + para multiplicarse y mantenerse con vida, cuando no se revierte, tiene el resultado inevitable del síndrome de inmunodeficiencia adquirida (SIDA), evento en el que los pacientes comienzan a presentar enfermedades secundarias como infecciones oportunistas y cáncer. Objetivo: Identificar los casos de linfoma de Hodgkin en pacientes VIH+ utilizando los antirretrovirales de alta eficacia. Método: Este es un estudio observacional transversal con diseño exploratorio y descriptivo y enfoque cualitativo, realizado durante octubre de 2018 a partir del análisis de 57 registros médicos de pacientes VIH + diagnosticados con cáncer y hospitalizados en un hospital ubicado en Fortaleza, CE. Resultados: Se identificaron un total de 21 cánceres que no definen el SIDA. De estos, los más comunes fueron cáncer de piel con 14,3% (3), seguido de cáncer de seno con 9,5% (2), linfoma de Hodgkin 9,5% (2) y cáncer de estómago con 9,5% (2) de los casos. Conclusión: Los datos obtenidos en el presente estudio colocan al linfoma de Hodgkin en segundo lugar entre los cánceres no definitorios de SIDA encontrados. Sin embargo, considerando el bajo número de casos resultantes de las limitaciones de la investigación, esta información no nos permite concluir acerca de la cantidad real de linfoma de Hodgkin entre los otros cánceres no definitorios de SIDA en pacientes VIH + en la localidad, ni estimar la participación del VIH, la carga viral, la condición inmune y las coinfecciones como factores de riesgo.

Protective Effect of Quercetin on Renal Tubular Cells and the Involvement with the Renin-Angiotensin-Aldosterone Axis

Abstract Ischemia-reperfusion (I/R) plays an important role in the process of acute kidney injury (AKI) due to the generation of reactive oxygen species (ROS). Substances of natural origin have been studied in the prevention of oxidative damage related to I/R. Quercetin is a flavonoid with antioxidant potential and modulate enzymes, such the inhibition of the Rennin-Angiotensin System (RAS). The aim of this study is to evaluate the nephroprotective effect of quercetin against the I/R and analyze the inhibition of RAS. Rhesus monkey Kidney Epithelial Cells (LLC-MK2 line) were submitted to an in vitro ischemia/reperfusion model. After the reperfusion cells were treated with quercetin, the cell viability was accessed by the MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) assay. Tubular cell damage was assessed by the Kidney Injury Molecule-1 (KIM-1) measurement. Oxidative stress was evaluated through Thiobarbituric Acid Reactive Substances (TBARS) and reduced glutathione (GSH). The evaluation of cell death and the mitochondrial depolarization were analyzed by flow cytometry. Quercetin prevents cell death reducing oxidative stress and preventing mitochondrial membrane depolarization. Molecular docking showed that quercetin prevents cell damage better than losartan and lisinopril, inhibitors of RAS. Quercetin has a potential to interact with type 1 angiotensin II receptor (AT1) with greater affinity through the formation of five hydrogen bonds of strong intensity.

Efeito nefroprotetor do α bisabolol na lesão renal aguda em modelos de isquemia reperfusão

A Isquemia/Reperfusão (I/R)é um fenômeno complexo, que contribui para a mortalidade e morbidade e é um fator predisponente para o estabelecimento da Lesão Renal Aguda (LRA). Várias estratégias e recursos são utilizados pelascélulas para prevenir ou diminuir a injúria celular causada pelo estresse oxidativo. Dessa forma, ressalta-se a importância do estudo utilizando substâncias como o (-)-α-Bisabolol, o qual apresenta um potencial antioxidante. Ademais, o estudo de ferramentaspara diagnóstico precoce do desenvolvimento da lesão renal utilizando biomarcadores cada vez mais sensíveis e específicos, como ressaltado neste trabalho o KIM-1, pode auxiliar na detecção da injúria e acompanhamento da progressão do processo de melhorae cura. Logo, o presente trabalho tem como objetivo estudar os possíveis efeitos nefroprotetores do (-)-α-Bisabolol na Lesão Renal Aguda (LRA) em modelos de Isquemia/Reperfusão (I/R), bem como estudar obiomarcador KIM-1 como preditor precoce da injúria renal. Ratos Wistar machos foram submetidos aoprocedimento cirúrgico de nefrectomia direita e clampeamento da artéria renal esquerda. Amostras de urina, sangue e tecido renal foram coletadas para avaliações adicionais. Um modelo in vitro de I/R foi realizado em cultura de linhagens de células tubulares renais LLC-MK2 para avaliar a viabilidade celular pelo ensaio de redução do MTT...

Ischemia / reperfusion (IR) isa complex phenomenon that contributes to mortality and morbidity and is a predisposing factor for the establishment of acute kidney injury (AKI). Various strategies and resources are used by cells to prevent or decrease the cellular injury caused by oxidative stress. Thus, it emphasizes the importance of studying using substances such as (-)-α-Bisabolol, which has an antioxidant potential. Furthermore, the study of strategies for early detection of developing kidney damage using increasingly sensitive and specific biomarkers, as pointed out in this paper the KIM-1, can aid in the detection of injury and follow the progression of improvement and healing process. Thus, this paper aims to study the possible nephroprotectiveseffects of (-)-α-Bisabolol in AcuteKidney Injury (AKI) in models of ischemia/reperfusion (I/R), as well as study the KIM-1 biomarker as a predictor early renal injury. Male Wistar rats underwent surgical procedure right nephrectomy and clamping of the left renal artery. Samples of urine, blood and kidney tissue were collected for further evaluation. An in vitro model of I/R was performed in a culture of renal tubular cell lines, LLC-MK2 to assess cell viability by the MTT reduction assay...