Estimated glomerular filtration rate in clinical practice: Consensus positioning of the Brazilian Society of Nephrology (SBN) and Brazilian Society of Clinical Pathology and Laboratory Medicine (SBPC/ML) / Estimativa da taxa de filtração glomerular na prática clínica: posicionamento consensual da Sociedade Brasileira de Nefrologia (SBN) e Sociedade Brasileira de Patologia Clínica e Medicina Laboratorial (SBPC/ML)

ABSTRACT Chronic kidney disease (CKD) represents one of today's main public health problems. Serum creatinine measurement and estimation of the glomerular filtration rate (GFR) are the main tools for evaluating renal function. There are several equations to estimate GFR, and CKD-EPI equation (Chronic Kidney Disease - Epidemiology) is the most recommended one. There are still some controversies regarding serum creatinine measurement and GFR estimation, since several factors can interfere in this process. An important recent change was the removal of the correction for race from the equations for estimating GFR, which overestimated kidney function, and consequently delayed the implementation of treatments such as dialysis and kidney transplantation. In this consensus document from the Brazilian Societies of Nephrology and Clinical Pathology and Laboratory Medicine, the main concepts related to the assessment of renal function are reviewed, as well as possible existing controversies and recommendations for estimating GFR in clinical practice.

RESUMO A doença renal crônica (DRC) representa um dos principais problemas de saúde pública da atualidade. A dosagem da creatinina sérica e a estimativa da taxa de filtração glomerular (TFG) são as principais ferramentas para avaliação da função renal. Para a estimativa da TFG, existem diversas equações, sendo a mais recomendada a CKD-EPI (Chronic Kidney Disease - Epidemiology). Existem ainda algumas controvérsias com relação à dosagem da creatinina sérica e da estimativa da TFG, uma vez que vários fatores podem interferir nesse processo. Uma importante mudança recente foi a retirada da correção por raça das equações para estimativa da TFG, que superestimavam a função renal, e consequentemente retardavam a implementação de tratamentos como diálise e transplante renal. Neste documento de consenso da Sociedade Brasileira de Nefrologia e Sociedade Brasileira de Patologia Clínica e Medicina Laboratorial são revisados os principais conceitos relacionados à avaliação da função renal, possíveis controvérsias existentes e recomendações para a estimativa da TFG na prática clínica.

Proteína C reactiva, aspectos cardiovasculares de una proteína de fase aguda: una actualización para el médico / C-reactive protein, cardiovascular issues of an acute-phase protein: an update for the clinician

Resumen La inflamación es un factor patogénico importante para el desarrollo de la enfermedad cardiovascular aterosclerótica. Actualmente, el biomarcador utilizado con mayor frecuencia que refleja la inflamación sistémica es la proteína C reactiva (PCR), una proteína de fase aguda producida principalmente por los hepatocitos bajo la influencia de la interleucina 6, la interleucina 1 beta y el factor de necrosis tumoral. La evidencia proveniente de estudios epidemiológicos ha demostrado una fuerte asociación entre las concentraciones elevadas de PCR en suero o plasma y la incidencia de un primer evento cardiovascular (incluido infarto agudo de miocardio, accidente vascular cerebral isquémico y muerte cardíaca súbita) en la población general, así como la recurrencia de eventos cardiovasculares adversos en los pacientes con enfermedad establecida. El valor aditivo que la medición de la PCR otorga a los factores de riesgo tradicionales se refleja en novedosas calculadoras de riesgo cardiovascular y en los actuales regímenes de intervención, que ya consideran a la PCR como objetivo terapéutico. Sin embargo, las variaciones en los niveles de PCR, que dependen del sexo, la etnia, el estado hormonal y algunas peculiaridades de los ensayos de medición, deben tenerse en cuenta al decidir implementar la PCR como un biomarcador útil en el estudio y el tratamiento de la enfermedad cardiovascular aterosclerótica. Esta revisión pretende ofrecer una visión actualizada de la importancia de medir la PCR como biomarcador de riesgo cardiovascular más allá de los factores tradicionales que estiman el riesgo de enfermedad aterosclerótica.

Abstract Inflammation is an important pathogenic factor for the development of atherosclerotic cardiovascular disease. Currently, the most frequently used biomarker reflecting systemic inflammation is C-reactive protein (CRP), an acute-phase protein produced primarily by hepatocytes under the influence of interleukin-6, interleukin-1 beta, and tumor necrosis factor. Growing evidence from epidemiological studies has shown a robust association between elevated serum or plasma CRP concentrations and the incidence of a first cardiovascular adverse event (including acute myocardial infarction, ischemic stroke, and sudden cardiac death) in the general population, as well as recurrence of major adverse cardiovascular events among patients with established disease. The additive value that CRP measurement gives to traditional risk factors is reflected in novel cardiovascular risk calculators and in current intervention regimens, which already consider CRP as a target therapeutic. However, the variations in CRP levels, that depend on sex, ethnicity, hormonal status, and some peculiarities of the measurement assays, must be taken into consideration when deciding to implement CRP as a useful biomarker in the study and treatment of atherosclerotic cardiovascular disease. This review aims to offer an updated vision of the importance of measuring CRP levels as a biomarker of cardiovascular risk beyond the traditional factors that estimate the risk of atherosclerotic disease.

Association of oropharyngeal colostrum administration with decreased inflammatory indices in premature newborns weighing less than 1500 g / Asociación de la administración de calostro orofaríngeo con la disminución de los índices inflamatorios en recién nacidos prematuros menor de 1500 g

Abstract Background: The administration of colostrum through its absorption at the oropharyngeal level stimulates the mucosa-associated lymphoid tissue, providing a local immunological protection barrier. The study aimed to investigate the association of oropharyngeal colostrum administration with the reduction of inflammatory indices. Materials and methods: This was an observational, ambispective, analytical study of newborns < 32 weeks of gestation at risk of sepsis. Oropharyngeal colostrum was administered at 0.2 mL every 4 h for 5 days. Inflammatory indices were analyzed. Statistical analysis included frequencies, percentages, mean and Standard deviation, contingency coefficient, and Kolmogorov–Smirnov test for the distribution curve of the numerical data. Results: There were 50 patients, 33 (66%) female and 17 (34%) male, with a median gestational age of 30-31 weeks (95% confidence interval [CI]). Nineteen patients had sepsis. A lower positivity rate in C-reactive protein was found, with a median of 0.5-0.6 (95% CI) at 5 days of colostrum administration versus 0.5-1.1 (95% CI) as the initial C-reactive protein. Analysis with χ2 yielded a p = 0.13, and the contingency coefficient showed a p = 0.196, indicating an association. Conclusion: Oropharyngeal colostrum administration was associated with a lower C-reactive protein positivity rate and clinical improvement in premature newborns at risk of sepsis.

Resumen Introducción: La administración del calostro a través de su absorción a nivel orofaríngeo estimula el tejido linfoide asociado a mucosas, proporcionando una barrera de protección local e inmunológica. Conocer la asociación de la administración de calostro orofaríngeo con la disminución de los índices inflamatorios. Material y métodos: Observacional, ambispectivo, analítico, recién nacidos < 32 semanas de gestación con riesgo de sepsis, se administró calostro orofaríngeo 0.2 ml cada 4 horas durante 5 días. se analizó índices inflamatorios, evolución clínica. Análisis estadístico: frecuencias, porcentajes, media y DS, coeficiente de contingencia y prueba de Kolmogorov Smirnov para la curva de distribución de los datos numéricos. Resultados: Fueron 50 pacientes, 33 (66%) femenino, 17 (34%) masculino, edad gestacional mediana 30-31 semanas (IC 95%), 19 pacientes cursaron con sepsis encontrando menor índice de positividad en la PCR, mediana de 0.5-0.6 (IC 95%) a los 5 días de administración de calostro vs 0.5-1.1 (IC 95%) como PCR inicial, analizando con Chi cuadrada con valor p = 0.13, mediante coeficiente de contingencia con p = 0.196, traduciendo asociación. Conclusión: La calostroterapia se asoció con menor índice de positividad en la PCR; clínicamente hacia la mejoría, en recién nacidos prematuros con riesgo de sepsis.

Epidemiological study of Hepatitis C in people deprived of liberty / Estudo epidemiológico da Hepatite C em pessoas privadas de liberdade

INTRODUCTION: The prevalence of hepatitis C (HCV) is high among prisoners. If untreated, a substantial number of patients progress to cirrhosis, hepatocarcinoma, or liver failure. World Health Organization aims to reduce the incidence of infection by 90% by 2030. OBJECTIVE: To describe the prevalence of anti-HCV and sociodemographic and clinical aspects, related to the presence of the antibody, in the population deprived of liberty. METHODS: Cross-sectional and epidemiological survey, with exploratory, observational, quantitative-analytical components. A simple random sample of 233 participants, with 95% Confidence Interval (CI) and, a 4% margin of error, was calculated for a population of 1,564 prisoners. The relationship between sociodemographic and clinical variables was evaluated, considering as outcome of the rapid test for anti-HCV results, using the associative measure Prevalence Ratio (PR) with a 95% CI. RESULTS: 240 people participated. The prevalence of anti-HCV was 2%, and the use of injectable drugs (PR 14.75; PRIC95% 2.09-104.28), being born in the decades of 1951 to 1980 (PR 9.28; PRIC95% 1.06-81.57) and be co-infected with hepatitis B virus (PR 10.75; PRIC95% 1.66-69.65) were the aspects that presented a relevant prevalence ratio for the presence of the virus, which could be generalized to the population. CONCLUSION: This is a population that is difficult to access, the study is relevant because it contributes to preventive measures of public health in the prison system. Moreover, it shows the need to implement measures to prevent and contain the spread of HCV, aiming at the elimination of hepatitis C in this population.

INTRODUÇÃO: A prevalência da hepatite C (HCV) é elevada entre os prisioneiros. Se não tratada, proporção substancial das infecções progride para cirrose, hepatocarcinoma ou insuficiência hepática. Organização Mundial de Saúde tem a meta de reduzir a incidência da infecção em 90% até 2030. OBJETIVO: Descrever a prevalência do anti-HCV e os aspectos sociodemográficos e clínicos, relacionados à presença do anticorpo, na população privada de liberdade. MÉTODOS: Estudo transversal por inquérito epidemiológico, com componente exploratório, observacional, quantitativo-analítico. Foi calculada amostra aleatória simples de 233 pessoas, Intervalo de Confiança (IC) 95%, margem de erro 4% para população de 1564 prisioneiros. Foi avaliada a relação entre os aspectos sociodemográficos e clínicos com o desfecho obtido pelo teste rápido para anti-HCV por meio da medida associativa Razão de Prevalência (RP) e IC de 95% para essa estimativa. RESULTADOS: Participaram 240 pessoas. A prevalência do anti-HCV foi de 2%, sendo que o uso de drogas injetáveis (RP 14,75; RPIC95% 2,09-104,28), ter nascido nas décadas de 1951 a 1980 (RP 9,28; RPIC95% 1,06-81,57) e ser coinfectado com o vírus da hepatite B (RP 10,75; RPIC95% 1,66-69,65) foram os aspectos que apresentaram razão de prevalência para a presença do vírus, passível de generalização para a população. CONCLUSÃO: Trata-se de população de difícil acesso, o estudo é relevante por contribuir para medidas preventivas de saúde pública no sistema prisional. Outrossim, mostra a necessidade de se implementar medidas para evitar e conter a disseminação de HCV, visando a microeliminação da hepatite C na população carcerária.

Una visión integral del manejo de la hepatitis C y el objetivo de erradicarla / A comprehensive view of hepatitis C management and the goal of eradication

La hepatitis C es una enfermedad viral causada por el virus de la hepatitis C (VHC), que fue identificada por primera vez en 1989 por un equipo de científicos liderado por Michael Houghton en Chiron Corporation. Esta forma de hepatitis era conocida como "hepatitis no-A no-B", ya que no se podía identificar el agente infeccioso responsable. Puede afectar a personas de diferentes géneros y orientaciones sexuales, incluidos los hombres que tienen sexo con hombres (HSH); y su transmisión ocurre a través de situaciones en las que hay un intercambio de sangre, como el uso compartido de agujas o equipo para la inyección de drogas, o durante prácticas sexuales que pueden causar microlesiones en la mucosa anal. Es importante destacar que la hepatitis C también puede transmitirse a través de otras vías, como la transfusión de sangre no segura, la exposición a instrumentos médicos contaminados, o el compartir objetos personales que puedan tener sangre infectada.

Hepatitis C is a viral disease caused by the hepatitis C virus (HCV), which was first identified in 1989 by a team of scientists led by Michael Houghton at Chiron Corporation. This form of hepatitis was known as "non-A non-B hepatitis" as the infectious agent responsible couldn't be identified. It can affect individuals of different genders and sexual orientations, including men who have sex with men (MSM); transmission occurs through situations involving blood exchange, such as needle sharing or equipment for drug injection, or during sexual practices that may cause microlesions in the anal mucosa. It's important to note that hepatitis C can also be transmitted through other routes, such as unsafe blood transfusion, exposure to contaminated medical instruments, or sharing personal items that may have infected blood.

Antivirales de acción directa contra la hepatitis C: revisión narrativa / Direct acting antivirals against hepatitis C: Literature review

Desde los años ochenta se ha explorado el tratamiento para el virus de la hepatitis C, aunque en ese entonces los medicamentos disponibles eran poco toleradas y poco eficaces. En el 2011, la introducción de antivirales de acción directa transformó significativamente el curso de la enfermedad, logrando tasas de curación superiores al 90 % en los pacientes. Este avance ha permitido prevenir complicaciones futuras con efectos adversos mínimos. La presente revisión aborda la línea de tiempo del descubrimiento de los antivirales, su mecanismo de acción, sus indicaciones y potencial impacto en la salud pública.

Since the 1980s, the treatment of hepatitis C has been explored, although at that time, the available medications were poorly tolerated and ineffective. In 2011, the introduction of direct-acting antivirals significantly transformed the course of the disease, achieving cure rates of over 90% in patients. This advance has made it possible to prevent future complications with minimal adverse effects. This review addresses the timeline of the discovery of antivirals, their mechanism of action, and their impact on medicine.

Validez de herramientas diagnósticas en pacientes pediátricos hospitalizados con diagnóstico presuntivo de dengue en un Hospital de Referencia de Paraguay / Validity of diagnostic tools in pediatric patients hospitalized with a presumptive diagnosis of dengue in a Reference Hospital in Paraguay

Introducción: El dengue es la enfermedad arboviral más común en los seres humanos. Un diagnóstico temprano y preciso del dengue puede respaldar el manejo clínico, la vigilancia y el control de la enfermedad y es fundamental, por ello en el diagnóstico del dengue es importante contar con pautas clínicas y epidemiológicas que permitan la identificación oportuna y una conducta terapéutica adecuada. Objetivos: Evaluar la validez de herramientas diagnósticas en pacientes pediátricos hospitalizados con diagnóstico presuntivo de dengue en un Hospital de Referencia de Paraguay durante los años de 2012 a 2020. Materiales y métodos: Estudio analítico de tipo observacional, retrospectivo correspondientes a pacientes pediátricos (0 a 18 años) internados en el Hospital de Referencia de Paraguay el periodo enero 2012 a julio 2020 con diagnostico presuntivo de dengue al ingreso. Se realizó́ un análisis bivariado relacionando las frecuencias de 20 grupos de criterios diagnósticos combinados y 3 criterios diagnósticos aislados (OMS 2009, nexo epidemiológico y antigenemia NS1 para dengue) con el gold standard de diagnóstico que fue la conversión serológica. Resultados: Participaron del estudio 342 sujetos. EL 44% tenía edad escolar y 70% tenía 5 años o más. El 52,76% (191) fueron masculinos. Se encontraron desnutrición y sobrepeso en el 13% y 2%, respectivamente. La combinación de proteína C reactiva con plaquetopenia se encontró́ en 0.45% de los pacientes sin dengue y en el 6% de los pacientes con diagnóstico final de dengue (p=0.004). Conclusión: Este resultado aporta la alternativa de uso de una combinación sencilla de exámenes de laboratorio que puede replicarse en salas de urgencias como en salas de internación en un primer contacto con pacientes febriles con sospecha de fiebre dengue.

Introduction: Dengue is the most common arboviral disease in humans. An early and accurate diagnosis of dengue can support the clinical management, surveillance and control of the disease and is essential, therefore in the diagnosis of dengue it is important to have clinical and epidemiological guidelines that allow timely identification and appropriate therapeutic conduct. Objectives: To evaluate the validity of diagnostic tools in pediatric patients hospitalized with a presumptive diagnosis of dengue in a Reference Hospital in Paraguay during the years 2012 to 2020. Materials and methods: Analytical study of case and control type, observational, longitudinal, retrospective corresponding to pediatric patients (0 to 18 years) admitted to the Reference Hospital of Paraguay from January 2012 to July 2020 with a presumptive diagnosis of dengue at income. A bivariate analysis was performed relating the frequencies of 20 groups of combined diagnostic criteria and 3 isolated diagnostic criteria (WHO 2009, epidemiological link and NS1 antigenemia for dengue) with the gold standard of diagnosis, which was serological conversion. Results: 342 subjects participated in the study. 44% were school age and 70% were 5 years old or older. 52.76% (191) were male. Malnutrition and overweight were found in 13% and 2%, respectively. The combination of C-reactive protein with thrombocytopenia was found in 0.45% of patients without dengue and in 6% of patients with a final diagnosis of dengue (p=0.004). Conclusion: This result provides the alternative of using a simple combination of laboratory tests that can be replicated in emergency rooms and inpatient wards in a first contact with febrile patients with suspected dengue fever.

Renal deficit and associated factors in children born with low birth weight / Déficit renal e fatores associados em crianças nascidas com baixo peso

ABSTRACT Introduction: Kidney problems may be due to low birth weight alone or may occur in association with other conditions. The objective this study was to evaluate the association between maternal and birth characteristics, anthropometric measurements, and kidney function deficit in low birth weight infants. Methods: Cross-sectional study with children who were born weighing < 2500 grams and were under outpatient follow-up. Maternal factors investigated were prenatal care and presence of hypertension, diabetes, and infection during pregnancy. The children's variables were sex, gestational age, birth weight, Apgar score, use of nephrotoxic medications, age, body weight at the time of evaluation, height, and serum creatinine and cystatin C dosages. The glomerular filtration rate (GFR) was estimated with the combined Zapittelli equation. Multivariate logistic regression model was used for identification of associated factors, with renal function deficit (GFR < 60 mL/min/1.73 m2) as the dependent variable. Results: Of the 154 children evaluated, 34.42% had kidney function deficit. Most of them had a gestational age > 32 weeks (56.6%), a mean birth weight of 1439.7 grams, and mean estimated GFR of 46.9 ± 9.3 mL/min/1.73 m2. There was a significant association of GFR < 60 mL/min/1.73 m2 with children's current weight and use of nephrotoxic drugs. Discussion: Children born with low birth weight had a high prevalence of kidney function deficit and current normal weight was a protective factor while the use of nephrotoxic drugs during perinatal period increased the chance of kidney deficit. These findings reinforce the need to evaluate the kidney function in these children, especially those who use nephrotoxic drugs.

RESUMO Introdução: Problemas renais podem ser devido apenas ao baixo peso ao nascer ou podem ocorrer em associação com outras condições. O objetivo deste estudo foi avaliar a associação entre características maternas e de nascimento, medidas antropométricas e déficit da função renal em bebês de baixo peso ao nascer. Métodos: Estudo transversal com crianças que nasceram com peso < 2500 gramas e estavam sob acompanhamento ambulatorial. Os fatores maternos investigados foram cuidados pré-natal e presença de hipertensão, diabetes e infecção durante a gravidez. As variáveis das crianças foram sexo, idade gestacional, peso ao nascer, índice Apgar, uso de medicamentos nefrotóxicos, idade, peso corporal no momento da avaliação, altura e dosagens séricas de creatinina e cistatina C. A taxa de filtração glomerular (TFG) foi estimada com a equação combinada de Zapittelli. Utilizou-se um modelo de regressão logística multivariada para identificação de fatores associados, com déficit da função renal (TFG < 60 mL/min/1,73 m2) como variável dependente. Resultados: Das 154 crianças avaliadas, 34,42% apresentaram déficit da função renal. A maioria tinha idade gestacional > 32 semanas (56,6%), peso médio ao nascer de 1439,7 gramas, e TFG média estimada de 46,9 ± 9,3 mL/min/1,73 m2. Houve uma associação significativa da TFG < 60 mL/min/1,73 m2 com o peso atual das crianças e o uso de medicamentos nefrotóxicos. Discussão: Crianças nascidas com baixo peso apresentaram alta prevalência de déficit da função renal e o peso atual normal foi um fator de proteção, enquanto o uso de medicamentos nefrotóxicos durante o período perinatal aumentou a chance de déficit renal. Estes achados reforçam a necessidade de avaliar a função renal destas crianças, especialmente aquelas que usam medicamentos nefrotóxicos.

25-hydroxycholesterol aggravates oxygen-glucose deprivation/reoxygenation-induced pyroptosis through promoting activation of NLRP3 inflammasome in H9C2 cardiomyocytes

25-hydroxycholesterol (25-HC) plays a role in the regulation of cell survival and immunity. However, the effect of 25-HC on myocardial ischemia/reperfusion (MI/R) injury remains unknown. Our present study aimed to investigate whether 25-HC aggravated MI/R injury through NLRP3 inflammasome-mediated pyroptosis. The overlapping differentially expressed genes (DEGs) in MI/R were identified from the GSE775, GSE45818, GSE58486, and GSE46395 datasets in Gene Expression Omnibus (GEO) database. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted using the database of Annotation, Visualization and Integration Discovery (DAVID). The protein-protein interaction (PPI) network of the overlapping DEGs was established using the Search Tool for the Retrieval of Interacting Genes (STRING) database. These bioinformatics analyses indicated that cholesterol 25-hydroxylase (CH25H) was one of the crucial genes in MI/R injury. The oxygen-glucose deprivation/reoxygenation (OGD/R) cell model was established to simulate MI/R injury. Western blot and RT-qPCR analysis demonstrated that CH25H was significantly upregulated in OGD/R-stimulated H9C2 cardiomyocytes. Moreover, knockdown of CH25H inhibited the OGD/R-induced pyroptosis and nod-like receptor protein 3 (NLRP3) inflammasome activation, as demonstrated by cell counting kit-8 (CCK8), lactate dehydrogenase (LDH), RT-qPCR, and western blotting assays. Conversely, 25-HC, which is synthesized by CH25H, promoted activation of NLRP3 inflammasome in OGD/R-stimulated H9C2 cardiomyocytes. In addition, the NLRP3 inhibitor BAY11-7082 attenuated 25-HC-induced H9C2 cell injury and pyroptosis under OGD/R condition. In conclusion, 25-HC could aggravate OGD/R-induced pyroptosis through promoting activation of NLRP3 inflammasome in H9C2 cells.

Ag85B with c-di-AMP as mucosal adjuvant showed immunotherapeutic effects on persistent Mycobacterium tuberculosis infection in mice

Tuberculosis (TB), caused by Mycobacterium tuberculosis, remains the leading cause of mortality by a single infectious agent in the world. M. tuberculosis infection could also result in clinical chronic infection, known as latent TB infection (LTBI). Compared to the current limited treatment, several subunit vaccines showed immunotherapeutic effects and were included in clinical trials. In this study, a subunit vaccine of Ag85B with a novel mucosal adjuvant c-di-AMP (Ag85B:c-di-AMP) was delivered intranasally to a persistent M. tuberculosis H37Ra infection mouse model, which also presented the asymptomatic characteristics of LTBI. Compared with Ag85B immunization, Ag85B:c-di-AMP vaccination induced stronger humoral immune responses, significantly higher CD4+ T cells recruitment, enhanced Th1/Th2/Th17 profile response in the lung, decreased pathological lesions of the lung, and reduced M. tuberculosis load in mice. Taken together, Ag85B:c-di-AMP mucosal route immunization provided an immunotherapeutic effect on persistent M. tuberculosis H37Ra infection, and c-di-AMP, as a promising potential mucosal adjuvant, could be further used in therapeutic or prophylactic vaccine strategies for persistent M. tuberculosis infection as well as LTBI.

Proteína-C reactiva de alta sensibilidad y homocisteína en pacientes con enfermedad cerebrovascular isquémica

Fundamento: la proteína C reactiva de alta sensibilidad (PCR-as) y la homocisteína (Hci) parecen relacionarse con la enfermedad cerebrovascular isquémica, pero sus hallazgos sobre el riesgo y pronóstico de esta enfermedad resultan controversiales y no concluyentes. Objetivo caracterizar la proteína C reactiva de alta sensibilidad y homocisteína en pacientes con enfermedad cerebrovascular isquémica. Métodos: se realizó un estudio descriptivo y retrospectivo de corte transversal en pacientes con enfermedad cerebrovascular isquémica, ingresados en el Servicio de Ictus del Instituto de Neurología y Neurocirugía entre 2016 y 2019. Se recogieron variables demográficas, manifestaciones clínicas, tiempo de evolución, etiología y localización del infarto y factores riesgo. Se cuantificaron la PCR-as (riesgo cardiovascular) y la Hci. Resultados las medias de PCR-as (7,0±8,3 mg/L) y Hci (17,1±7,3 µM) fueron elevadas. El riesgo cardiovascular moderado y alto se presentaron en igual proporción (46,8 %). Hubo diferencias estadísticas en la relación entre el riesgo cardiovascular y la edad (p=0,00); pero ni el tiempo de evolución ni los factores de riesgo de la enfermedad mostraron este comportamiento. Los pacientes con riesgo cardiovascular alto (PCR-as >3 mg/L) y elevada Hci (>15 (M) exhibieron mayores frecuencias de etiologías aterotrombótica o cardioembólica. Conclusiones el riesgo cardiovascular aumenta en la medida que se incrementa la edad de pacientes con enfermedad cerebrovascular isquémica. Las características demográficas, clínicas y neurológicas no mostraron relación con el alto riesgo cardiovascular y los valores elevados de Hci, aunque se encontró una tendencia asociativa de la etiología aterotrombótica con el incremento de PCR-as y Hci.

Foundation: High-sensitivity C-reactive protein and homocysteine seem to be related to ischemic cerebrovascular disease, but their findings on the risk and prognosis of this disease are controversial and inconclusive. Objective: to characterize high sensitivity C-reactive protein and homocysteine in patients with ischemic cerebrovascular disease. Methods: a descriptive and retrospective cross-sectional study was carried out in patients with ischemic cerebrovascular disease, admitted to the Stroke Service of the Neurology and Neurosurgery Institute between 2016 and 2019. Demographic variables, clinical manifestations, time of evolution, etiology and infarction location, risk factors. High-sensitivity C-reactive protein (cardiovascular risk) and homocysteine were quantified. Results: the means of C-reactive protein (7.0±8.3 mg/L) and homocysteine (17.1±7.3 µM) were high. Moderate and high cardiovascular risk occurred in equal proportions (46.8%). There were statistical differences in the relationship between cardiovascular risk and age (p=0.00); but neither the time of evolution nor the risk factors of the disease showed this behavior. Patients with high cardiovascular risk (hs-CRP >3 mg/L) and high homocysteine (>15 (M), exhibited higher frequencies of atherothrombotic or cardioembolic etiologies. Conclusions: cardiovascular risk increases as the age of patients with ischemic cerebrovascular disease increases. Demographic, clinical and neurological characteristics did not show a relationship with high cardiovascular risk and high homocysteine values, although an associative trend of atherothrombotic etiology was found with increased high-sensitivity C-reactive protein and homocysteine.

Endotoxin test by recombinant Factor C for 0.9% sodium chloride injection

Endotoxin contamination is a threat to the safety of pharmaceutical products, especially parenteral drugs. Any sterile and/or pyrogen-free pharmaceutical product requires regulatory specifications to ensure safe patient use. This study covers the performance evaluation study of an endotoxin quantitation commercial kit by recombinant Factor C (rFC), Endozyme II® Go, for 0.9% sodium chloride injection. The samples were spiked with endotoxin solutions between 0.0005 and 10 EU/mL and tested by the rFC kit to evaluate precision, accuracy, detection and quantification limits, linearity, and robustness. Each of the six points was assayed at least five times.The relative standard deviation for precision testing ranged from 1.9 to 8.3%. The recovery accuracy values of endotoxin were between 61% and 125% for the range from 0.005 to 10 EU/mL. The results demonstrated that the rFC method allows endotoxin quantification with accuracy, precision, specificity, and linearity for the range of 0.005 and 10 EU/mL for 0.9% sodium chloride injection. (AU)

A contaminação por endotoxinas é uma ameaça à segurança dos produtos farmacêuticos, especialmente dos medicamentos parenterais. Qualquer produto farmacêutico estéril e/ou livre de pirogênios requer especificações regulatórias para garantir a segurança de uso para o paciente. Este estudo abrange o estudo de avaliação de desempenho empregando o kit comercial Endozyme II® Go para quantificação de endotoxina, por Fator C recombinante (FCr), em amostras de cloreto de sódio 0,9% para uso parenteral. As amostras foram fortificadas com cinco concentrações distintas de soluções de endotoxina na faixa entre 0,0005 e 10 UE/mL. Cada um dos cinco níveis foi testado pelo menos cinco vezes para avaliação dos critérios de precisão, exatidão, limites de detecção e quantificação, linearidade e robustez. O desvio padrão relativo para os testes de precisão variou de 1,9 a 8,3%. Os valores de recuperação de endotoxina para o parâmetro exatidão estiveram compreendidos entre 61% e 125%. Os resultados demonstraram que o método por FCr permite a quantificação de endotoxinas com exatidão, precisão, especificidade e linearidade para a faixa de 0,005 e 10 UE/mL em amostras de cloreto de sódio 0,9% para uso parenteral. (AU)

Correlation analysis of serum lipids, HbA1C levels and insulin resistance in obese type 2 diabetes patients / 公共卫生与预防医学

Objective To investigate the changes of blood lipid and glycosylated hemoglobin (HbA1c) levels in obese type 2 diabetes (T2DM) patients and their relationship with insulin resistance (Homa-IR). Methods A total of 120 cases of T2DM newly diagnosed in Motuo County, Tibet from February to October 2022 were selected as the observation group. According to BMI, the patients were divided into diabetes normal weight group (46 cases), overweight group (43 cases) and obesity group (31 cases); 145 healthy subjects were selected as the control group. The levels of HbA1c, fasting blood glucose (FPG), fasting insulin (FINS), serum total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL-C), and low-density lipoprotein (LDL-C) were detected in the study subjects, and Homa-IR and Homa-β indices were calculated. The height, weight, and abdominal circumference were measured. The differences in the levels of the above indicators between the observation group patients and the control group, as well as among various subgroups within the observation group were compared. The influencing factors of Homa-IR in obese T2DM patients were analyzed. Results Compared with the control group, a significant increase in BMI, abdominal circumference, blood pressure, HbA1c, FBG, FINS, TC, TG, LDL-C, UA, visceral fat area, and the levels of Home-IR and Home-β was found in the observation group (all P<0.05). There were significant differences in BMI, abdominal circumference, and the levels of FINS, Homa IR, Homa-β, and HbA1c in diabetes patients with different BMI (all P<0.05). Correlation analysis showed that TG levels in obese T2DM patients in the observation group were significantly correlated with HbA1c (r=0.396, P=0.027), Homa-IR (r=0.405, P=0.024), and Home-β (r=-0.401, P=0.025); LDL-C was significantly correlated with Homa-IR (r=0.411, P=0.022) and Homa-β (r=-0.412, P=0.021); HbA1c was significantly positively correlated with BMI (r=0.371, P=0.040). Conclusion Insulin resistance is closely related to TG, LDL-C, and BMI in obese T2DM patients from the Motuo ethnic minority of Tibet, suggesting that these factors may play a role in the occurrence of T2DM.

Improvement effects of Runchang granules on the constipation in mice and its mechanism / 中国药房

OBJECTIVE To investigate the improvement effects of Runchang granules on the constipation in mice and its potential mechanism. METHODS The mice were randomly divided into normal control group， model group， Runchang granules low-dose and high-dose groups （5， 10 g/kg）， mosapride group （0.003 g/kg， positive control）， with 6 mice in each group. The latter 4 groups were given loperamide intragastrically （0.004 g/kg）， twice a day， for 3 consecutive days. Normal control group and model group were given purified water intragastrically， and administration groups were given relevant medicine intragastrically for 7 consecutive days. After the last medication， fecal moisture content and intestinal motility of mice were determined， while the structures of colon and ileum， and the secretion of colonic mucus were observed. Protein expressions of tyrosine kinase receptor （c-kit）， mucin 2 （MUC2） and stem cell factor （SCF） were determined in colon； meanwhile， the mRNA expression levels of inflammatory factors [tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， IL-1β， inducible nitric oxide synthase （iNOS）] as well as factors related to promoting intestinal motility [neuronal nitric oxide synthase （nNOS）， smooth muscle myosin light chain kinase （smMLCK）， 5-hydroxytryptamine 4 receptor （5-HT4R）， MUC2， SCF， c-kit] were determined. RESULTS Compared with model group， the fecal water content， intestinal propulsion rate， protein expression of c-kit in colon， relative expressions of MUC2 and SCF protein， and mRNA expressions of factors related to promoting intestinal motility （except for nNOS and SCF in Runchang granules low-dose group） were all increased significantly in Runchang granules low-dose and high-dose groups， and mosapride group （P＜0.05 or P＜0.01）. mRNA expression levels of inflammatory factors were decreased significantly（P＜0.05 or P＜0.01）. Both colon and ileum injuries improved， and the secretion of colon mucus was increased significantly in Runchang granules high-dose group （P＜0.01）. CONCLUSIONS Runchang granules have laxative effect and can improve constipation in mice， and its mechanism may be related to the promotion of the secretion of colon mucus and MUC2 expression， and the activation of SCF/c-kit signaling pathway.

Research progress on m5C methylation and its prospects in tumor immunotherapy / 口腔疾病防治

@#Epigenetic modification plays an important role in the biological regulatory process of eukaryotic cells. Tumor immunotherapy is an important means and clinical strategy for the treatment of some cancers. 5-Methylcytosine (m5C) is an important component of the epigenetic regulatory network discovered after m6A and has become a new topic for life science research in recent years. The m5C methylation of RNA can affect the fate of the modified RNA molecules and play an important role in various biological processes, including RNA stability, protein synthesis and transcriptional regulation. Recent studies have shown that m5C writers, erasers and readers are related to a variety of cellular biological processes and systemic diseases, including the occurrence, metastasis and tumor immune microenvironment. m5C methylation can widely affect gene expression and the biological process of tumorigenesis and development at multiple levels, but its specific mechanism and potential interaction with other epigenetic modifications in tumor immunotherapy are still unclear, and its regulatory mechanism, risk assessment and role in targeted therapy for malignant tumors need to be further studied. This article will review the dynamic regulatory network of m5C, the biological role of m5C modification in solid tumors and potential targets in tumor immunotherapy.

Antibacterial activity of Crude Momordica charantia, Cassia alata, and Allium sativum methanolic extracts on Leptospira interrogans serovar Manilae

Background and Objective@#Leptospirosis is a disease caused by pathogenic Leptospira prevalent in tropical countries like the Philippines. Some studies have shown that the role of currently used antibiotics for leptospirosis is unclear since trials have found no significant benefit to patient outcomes compared to placebo. This signals the need for alternative therapies, such as herbal medicines, which may provide effective therapeutic regimens in treating this infection. In this study, we characterized the antibacterial potential of three Philippine herbal medicines against Leptospira interrogans. @*Methods@#Crude methanolic extracts of Momordica charantia, Cassia alata, and Allium sativum were subjected to an optimized broth microdilution assay against L. interrogans, utilizing the resazurin-resorufin reaction as a cell proliferation and viability indicator. @*Results@#The respective minimum inhibitory concentrations of the plants were found to be as follows: 1.25 mg/mL (M. charantia), 2.5 mg/mL (C. alata), and >5 mg/mL (A. sativum). @*Conclusions@#Among the three herbal medicines, M. charantia and C. alata proved to have antibacterial activity against L. interrogans. Given the promising potential of two of these plant extracts, exploring the use of other solvents to extract natural compounds from these plants, and discovering possible synergistic effects between these plants and conventional antibiotics may be worthwhile.

Analysis on risk factors of clopidogrel resistance in patients with ischemic stroke / 药学实践与服务

Objective To investigate the risk factors of drug resistance in patients with ischemic stroke by clopidogrel therapy and provide references for promoting clinical individualized drug therapy. Methods A total of 202 inpatients diagnosed with ischemic stroke were admitted and given dual anti-treatment (aspirin+clopidogrel). CYP2C19 genotype was detected by microarray hybridization during hospitalization, and CYP2C19 gene polymorphisms were classified into fast metabolism group, medium metabolism group and slow metabolism group according to the type of drug metabolism. Patients were tested for platelet inhibition induced by adenosine diphosphate (ADP) according to thromboelastographic (TEG) on 7~14 d of drug administration. ADP <30% was classified as clopidogrel drug resistance group and ADP ≥30% as non-resistance group. Logistic regression analysis was used to study the risk factors for the development of clopidogrel resistance. Results Among 202 patients with ischemic stroke, 87 were in the resistant group and 115 in the non-resistant group. The proportion of patients with clopidogrel resistance combined with diabetes and the level of white blood cell count were higher than that in the non-resistant group, and the differences were statistically significant (P<0.05).The proportion of patients with clopidogrel resistance in the CYP2C19 intermediate metabolism group was significantly higher than that in the fast metabolism group, and the rate of platelet inhibition was also significantly lower than that in the fast metabolism group, all with statistically significant differences (P<0.05). Conclusion Combined diabetes mellitus, high white blood cell count levels and CYP2C19 mid-metabolic phenotype are independent risk factors for the development of clopidogrel resistance in patients with ischemic stroke.

Gastrodin Inhibits Non-alcoholic Fatty Liver Disease via Mediating SREBP1c Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo observe the effect of gastrodin on the steroid regulatory element-binding protein 1c （SREBP1c） signaling pathway in high-fat high-cholesterol diet （HFHC）-induced mice and explore the mechanism of gastrodin in the treatment of non-alcoholic fatty liver disease （NAFLD）. MethodEight-week-old male C57BL/6J mice were used in vivo and divided into the following four groups， with six mice in each group： normal group， gastrodin group （50 mg·kg-1）， model group， and model + gastrodin group （50 mg·kg-1）. NAFLD model was established by feeding mice with HFHC for four weeks， and the mice were euthanized and the liver tissues were collected after four weeks. In vitro experiments were performed using Huh7 cells which were divided into five groups， and induced with free fatty acids （FFA， 200 μmol·L-1， oleic acid-palmitic acid 2∶1） to establish an NAFLD cell model. After 24 h， different concentrations of gastrodin （0， 5， 10， 20， and 40 μmol·L-1） were added to each group and cultured for another 24 h. Oil red O staining was used to detect lipid accumulation in mouse liver and Huh7 cells. Hematoxylin-eosin （HE） staining was used to observe pathological changes in liver tissue. Levels of serum total cholesterol （TC）， low-density lipoprotein cholesterol （LDL-C）， and triglycerides （TG） were measured using an automatic biochemical analyzer. Relevant assay kits were used to detect liver TC， TG， and FFA levels. Real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot were used to detect the expression of lipid synthesis-related proteins fatty acid synthase （FASN）， acetyl-CoA carboxylase 1 （ACC1）， and stearoyl-CoA desaturase 1 （SCD1）. ResultCompared with the normal group， the model group showed significantly increased serum TC， LDL-C， and TG levels （P<0.01）， liver TC， TG， and FFA levels （P<0.01）， increased lipid accumulation in Huh7 cells （P<0.01）， and significantly increased expression levels of lipid synthesis-related genes SREBP1c， FASN， ACC1， and SCD1 in mice and Huh7 cells （P<0.01）. Compared with the model group， after gastrodin treatment， the serum TC， LDL-C， and TG levels in mice significantly decreased （P<0.05， P<0.01）， the severity of fatty liver disease improved significantly， liver TC， TG， and FFA levels decreased significantly （P<0.05， P<0.01）， lipid accumulation in Huh7 cells decreased significantly （P<0.05， P<0.01）， the expression levels of lipid synthesis-related genes SREBP1c， FASN， ACC1， and SCD1 in mice and Huh7 cells decreased significantly （P<0.05， P<0.01）. ConclusionGastrodin can reduce hepatic lipid accumulation and blood lipid levels， improve HFHC-induced NAFLD， and its mechanism of action may be related to the regulation of the SREBP1c lipid synthesis-related signaling pathway.

Application status and prospect of organ from hepatitis C donor in solid organ transplantation / 器官移植

As a marginal organ donor, organs from hepatitis C donors have been applied in solid organ transplantation. While effectively alleviating the shortage of organs, it also faces certain challenges, such as the spread of hepatitis C virus (HCV). With the emergence and application of direct-acting antiviral agent, the cure of hepatitis C has gradually become a reality, laying the foundation for hepatitis C patients to become organ transplant donors. At present, with adjuvant treatment using antiviral drugs, certain efficacy has been achieved in solid organ transplantation from hepatitis C donors. In this article, research progress in kidney, heart, lung and liver transplantation from hepatitis C donors, the application of hepatitis C donors in solid organ transplantation and the safety and effectiveness of antiviral drugs were reviewed, and the feasibility of hepatitis C donors in solid organ transplantation was evaluated, aiming to provide reference for expanding the donor pool of organ transplantation and shortening the waiting time for organ transplantation in patients with end-stage diseases.

Construction of recombinant adenovirus expression vector of avian reovirus σC protein and its effect on proliferation of hepatocellular carcinoma cells / 中国生物制品学杂志

@#Objective To construct the recombinant adenovirus vector pAd-σC for the expression of avian reovirus(ARV)aC protein and to detect its effects on the proliferation of hepatocellular carcinoma cells,in order to build up a basis for the development of novel anti-tumor vaccines.Methods The recombinant shuttle vector pShuttle-σC was constructed by PCR amplification of ARV σC gene,and then transformed into competent BJ5183 cells containing the adenovirus vector pAdessy-1.The recombi-nant adenovirus vector pAd-σC was obtained by homologous recombination,and the virus was packaged in HEK293 cells.The virus titer was measured by TCID_(50),the expression of σC protein was determined by Western blot and ELISA,and the effect of virus on the proliferation of human hepatocellular carcinoma cells SMMC7721 was detected by CCK-8 assay.Results The recombinant shuttle vector pShuttle-σC was confirmed to be constructed correctly by double enzyme digestion and sequen-cing,and the recombinant adenovirus vector pAd-σC was constructed correctly as identified by colony PCR.σC protein was successfully expressed in hepatocellular carcinoma cells SMMC7721.The recombinant adenovirus Ad-σC had a titer of 10~(7.5)/0.1 mL,which inhibited the proliferation of hepatocellular carcinoma cells SMMC7721.Conclusion The recombinant adenovirus vector pAd-trC containing ARV σC gene was successfully constructed,and its inhibitory effect on tumor cell proliferation was preliminarily analyzed,which lays a foundation for revealing the molecular mechanism of ARV oncolytic effect and further developing novel anti-tumor biological preparation.