Associations among environmental exposure to trace elements and biomarkers of early kidney damage in the pediatric population.

BACKGROUND: In kidney damage, molecular changes can be used as early damage kidney biomarkers, such as Kidney Injury Molecule-1 and Neutrophil gelatinase-associated lipocalin. These biomarkers are associated with toxic metal exposure or disturbed homeostasis of trace elements, which might lead to serious health hazards. This study aimed to evaluate the relationship between exposure to trace elements and early damage kidney biomarkers in a pediatric population. METHODS: In Tlaxcala, a cross-sectional study was conducted on 914 healthy individuals. The participants underwent a medical review and a socio-environmental questionnaire. Five early damage kidney biomarkers were determined in the urine with Luminex, and molybdenum, copper, selenium, nickel, and iodine were measured with ICP-Mass. RESULTS: The eGFR showed a median of 103.75 mL/min/1.73 m2. The median levels for molybdenum, copper, selenium, nickel, and iodine were 24.73 ng/mL, 73.35 ng/mL, 4.78 ng/mL, 83.68 ng/mL, and 361.83 ng/mL, respectively. Except for molybdenum and nickel, the other trace elements had significant associations with the eGFR and the early kidney damage biomarkers. Additionally, we report the association of different exposure scenarios with renal parameters. DISCUSSION: and Conclusions. Among the explored metals, exposure to Cu and iodine impairs renal function. In contrast, Se may manifest as a beneficial metal. Interactions of Mo-Se and Mo-Iodine seem to alter the expression of NGAL; Mo-Cu for CLU; Mo-Cu, Mo-Se, and Mo-iodine for Cys-C and a-1MG; and Mo-Cu and Mo-iodine for KIM-1; were noticed. Our study could suggest that trace element interactions were associated with early kidney damage biomarkers.

Endothelial biomarkers (Von willebrand factor, BDCA3, urokinase) as predictors of mortality in COVID-19 patients: cohort study.

BACKGROUND: SARS-CoV-2 is a systemic disease that affects endothelial function and leads to coagulation disorders, increasing the risk of mortality. Blood levels of endothelial biomarkers such as Von Willebrand Factor (VWF), Thrombomodulin or Blood Dendritic Cell Antigen-3 (BDCA3), and uUokinase (uPA) increase in patients with severe disease and can be prognostic indicators for mortality. Therefore, the aim of this study was to determine the effect of VWF, BDCA3, and uPA levels on mortality. METHODS: From May 2020 to January 2021, we studied a prospective cohort of hospitalized adult patients with polymerase chain reaction (PCR)-confirmed COVID-19 with a SaO2 ≤ 93% and a PaO2/FiO2 ratio < 300. In-hospital survival was evaluated from admission to death or to a maximum of 60 days of follow-up with Kaplan-Meier survival curves and Cox proportional hazard models as independent predictor measures of endothelial dysfunction. RESULTS: We recruited a total of 165 subjects (73% men) with a median age of 57.3 ± 12.9 years. The most common comorbidities were obesity (39.7%), hypertension (35.4%) and diabetes (30.3%). Endothelial biomarkers were increased in non-survivors compared to survivors. According to the multivariate Cox proportional hazard model, those with an elevated VWF concentration ≥ 4870 pg/ml had a hazard ratio (HR) of 4.06 (95% CI: 1.32-12.5) compared to those with a lower VWF concentration adjusted for age, cerebrovascular events, enoxaparin dose, lactate dehydrogenase (LDH) level, and bilirubin level. uPA and BDCA3 also increased mortality in patients with levels ≥ 460 pg/ml and ≥ 3600 pg/ml, respectively. CONCLUSION: The risk of mortality in those with elevated levels of endothelial biomarkers was observable in this study.

Seasonal and Spatial Variability of PM2.5 Concentration, and Associated Metal(loid) Content in the Toluca Valley, Mexico.

This study provides evidence of the seasonal and spatial variation of metal(lloid)s in particulate matter minor to 2.5 microns (PM2.5) in the Toluca Valley Metropolitan Area (TVMA), the fifth largest urban center in Mexico. Four sites were sampled between 2013 and 2014, which included urban and industrial areas, in the dry-cold (November-February) and dry-hot (March-May) seasons; PM2.5 was collected using high- and medium-volume samplers. Metal(lloid) concentrations in PM2.5 were analyzed using inductively coupled plasma‒mass spectrometry (ICP‒MS). The highest 24-hour PM2.5 concentration in the northern area was observed, and the PM2.5 concentrations were independent of the season. Five metal(lloid)s with a recovery percentage above 80% were considered to be reported (Co, Cr, Cu, Mn, and Sb). The maximum concentrations of metal(lloid)s were observed during the dry-cold season, and concentrations were up to one hundred or thousand fold with respect to the dry-hot season. The 24-hour PM2.5 and metal(lloid) concentrations exceeded national and international guidelines to protect population health.

Acute and subchronic exposure to air particulate matter induces expression of angiotensin and bradykinin-related genes in the lungs and heart: Angiotensin-II type-I receptor as a molecular target of particulate matter exposure.

BACKGROUND: Particulate matter (PM) adverse effects on health include lung and heart damage. The renin-angiotensin-aldosterone (RAAS) and kallikrein-kinin (KKS) endocrine systems are involved in the pathophysiology of cardiovascular diseases and have been found to impact lung diseases. The aim of the present study was to evaluate whether PM exposure regulates elements of RAAS and KKS. METHODS: Sprague-Dawley rats were acutely (3 days) and subchronically (8 weeks) exposed to coarse (CP), fine (FP) or ultrafine (UFP) particulates using a particulate concentrator, and a control group exposed to filtered air (FA). We evaluated the mRNA of the RAAS components At1, At2r and Ace, and of the KKS components B1r, B2r and Klk-1 by RT-PCR in the lungs and heart. The ACE and AT1R protein were evaluated by Western blot, as were HO-1 and γGCSc as indicators of the antioxidant response and IL-6 levels as an inflammation marker. We performed a binding assay to determinate AT1R density in the lung, also the subcellular AT1R distribution in the lungs was evaluated. Finally, we performed a histological analysis of intramyocardial coronary arteries and the expression of markers of heart gene reprogramming (Acta1 and Col3a1). RESULTS: The PM fractions induced the expression of RAAS and KKS elements in the lungs and heart in a time-dependent manner. CP exposure induced Ace mRNA expression and regulated its protein in the lungs. Acute and subchronic exposure to FP and UFP induced the expression of At1r in the lungs and heart. All PM fractions increased the AT1R protein in a size-dependent manner in the lungs and heart after subchronic exposure. The AT1R lung protein showed a time-dependent change in subcellular distribution. In addition, the presence of AT1R in the heart was accompanied by a decrease in HO-1, which was concomitant with the induction of Acta1 and Col3a1 and the increment of IL-6. Moreover, exposure to all PM fractions increased coronary artery wall thickness. CONCLUSION: We demonstrate that exposure to PM induces the expression of RAAS and KKS elements, including AT1R, which was the main target in the lungs and the heart.

On the ultrasonic degradation of Rhodamine B in water: kinetics and operational conditions effect.

The aim of this present study was to investigate the degradation of Rhodamine B (RhB) in aqueous solution under the influence of ultrasound irradiation. An ultrasonic reactor was used to investigate the effect of different operational parameters such as dye initial concentration, ultrasound power, pH and electrical conductivity. The results showed an increase in decolourization rate with decreasing pH, but colour removal efficiency decreased with increasing initial dye concentration. It was found that an optimum electrical conductivity of the solution exists on enhancing the degree of RhB degradation. Sonolytic degradation data from the present and other works in the literature were analysed by Langmuir-type kinetics. The apparent reaction rate constant was strongly influenced by both irradiation power density and frequency, and based on the experimental data a mathematical correlation between them was obtained.

Impact of Fluoride Exposure on Rat Placenta: Foetal/Placental Morphometric Alterations and Decreased Placental Vascular Density.

Inorganic fluoride is a geogenic and anthropogenic contaminant widely distributed in the environment and commonly identified in contaminated groundwater. There is limited information on the effect of fluoride exposure on pregnancy. The aim of this study was to evaluate possible placental alterations of fluoride exposure in a rat model simulating preconception and pregnancy exposure conditions in endemic areas. Fluoride exposure was administered orally to foetuses of dams exposed to 2.5 and 5 mg fluoride/kg/d. Foetal weight, height, foetal/placental weight ratio, placental zone thickness, levels of malondialdehyde (MDA) and vascular endothelial growth factor-A (VEGF-A) and vascular density in placental tissue were evaluated. The results showed a nonlinear relationship between these outcomes and the dose of fluoride exposure. In addition, a significant increase in the fluoride concentration in placental tissue was observed. The group that was exposed to 2.5 mg fluoride/kg/d had a greater increase in both MDA levels and VEGF-A levels than the higher dose group. A significant increase in the thickness of the placental zones and a decrease in the vascular density of the labyrinth zone area were also observed in the fluoride-exposed groups. In conclusion, the data obtained demonstrate that fluoride exposure results in morpho-structural alterations in the placenta and that non-monotonic changes in MDA, VEGF-A levels and placental foetal weight ratio were at environmentally relevant concentrations.

Inflammation- and cancer-related microRNAs in rat renal cortex after subchronic exposure to fluoride.

The proximal tubule is a target of subchronic exposure to fluoride (F) in the kidney. Early markers are used to classify kidney damage, stage, and prognosis. MicroRNAs (miRNAs) are small sequences of non-coding single-stranded RNA that regulate gene expression and play an essential role in developing many pathologies, including renal diseases. This study aimed to evaluate the expression of Cytokine-Chemokine molecules (IL-1α/1ß/4/6/10, INF-γ, MIP-1α, MCP-1, RANTES, and TGF ß1/2/3) and inflammation-related miRNAs to evidence the possible renal mechanisms involved in subchronic exposure to F. Total protein and miRNAs were obtained from the renal cortex of male Wistar rats exposed to 0, 15 and 50 mg NaF/L through drinking water during 40 and 80 days. In addition, cytokines-chemokines were analyzed by multiplexing assay, and a panel of 77 sequences of inflammatory-related miRNAs was analyzed by qPCR. The results show that cytokines-chemokines expression was concentration- and time-dependent with F, where the 50 mg NaF/L were the main altered groups. The miRNAs expression resulted in statistically significant differences in thirty-four miRNAs in the 50 mg NaF/L groups at 40 and 80 days. Furthermore, a molecular interaction network analysis was performed. The relevant pathways modified by subchronic exposure to fluoride were related to extracellular matrix-receptor interaction, Mucin type O-glycan biosynthesis, Gap junction, and miRNAs involved with renal cell carcinoma. Thus, F-induced cytokines-chemokines suggest subchronic inflammation; detecting miRNAs related to cancer and proliferation indicates a transition from renal epithelium to pathologic tissue after fluoride exposure.

Effect of smoking on the redox status of knee osteoarthritis: A preliminary study.

Even though smoking has been scarcely studied in osteoarthritis (OA) etiology, it is considered a controversial risk factor for the disease. Exposure to tobacco smoke has been reported to promote oxidative stress (OS) as part of the damage mechanism. The aim of this study was to assess whether smoking increases cartilage damage through the generation of OS. Peripheral blood (PB) and synovial fluid (SF) samples from patients with OA were analyzed. The samples were stratified according to smoking habit, Kellgren-Lawrence score, pain, and cotinine concentrations in PB. Malondialdehyde (MDA), methylglyoxal (MGO), advanced protein oxidation products (APOPs), and myeloperoxidase (MPO) were assessed; the activity of antioxidant enzymes such as gamma-glutamyl transferase (GGT), glutathione S-transferase (GST) and catalase (CAT), as well as the activity of arginase, which favors the destruction of cartilage, was determined. When stratified by age, for individuals <60 years, the levels of MDA and APOPs and the activity of MPO and GST were higher, as well as antioxidant system activity in the smoking group (OA-S). A greater degree of pain in the OA-S group increased the concentrations of APOPs and arginase activity (P < 0.01 and P < 0.05, respectively). Arginase activity increased significantly with a higher degree of pain (P < 0.01). Active smoking can be an important risk factor for the development of OA by inducing systemic OS in young adults, in addition to reducing antioxidant enzymes in older adults and enhancing the degree of pain and loss of cartilage.

Plasma Endothelial and Oxidative Stress Biomarkers Associated with Late Mortality in Hospitalized COVID-19 Patients.

BACKGROUND: Coronavirus infectious disease 2019 (COVID-19) is a significant public health problem worldwide. COVID-19 increases the risk of non-pulmonary complications such as acute myocardial injury, renal failure, thromboembolic events, and multi-organic damage. Several studies have documented increased inflammation molecules, endothelial dysfunction biomarkers, and dysregulation of coagulation factors in COVID-19 patients. In addition, endothelium dysfunction is exacerbated by the oxidative stress (OxS) promoted by endocrine and cardiovascular molecules. Our objective was to evaluate whether endothelial and OxS biomarkers were associated with mortality in hospitalized COVID-19 patients. METHODS: A prospective cohort study was performed. Patients ≥18 years old with confirmed COVID-19 that required hospitalization were included in a prospective cohort study. Endothelium and oxidative stress biomarkers were collected between 3 and 5 days after admission. RESULTS: A total of 165 patients were evaluated; 56 patients succumbed. The median follow-up was 71 days [23-129]. Regarding endothelial dysfunction and OxS biomarkers, patients who did not survive had higher levels of nitrates (0.4564 [0.1817-0.6761] vs. 0.2817 [0.0517-0.5], p = 0.014), total nitrates (0.0507 [-0.0342-0.1809] vs. -0.0041 [-0.0887-0.0909], p = 0.016), sE-Selectin (1.095 [0.86-1.495] vs. 0.94 [0.71-1.19], p = 0.004), and malondialdehyde (MDA) (0.50 [0.26-0.72] vs. 0.36 [0.23-0.52], p = 0.010) compared to patients who survived. Endothelial and OxS biomarkers independently associated with mortality were sE-selectin (HR:2.54, CI95%; from 1.11 to 5.81, p = 0.027), nitrates (HR:4.92, CI95%; from 1.23 to 19.63, p = 0.024), and MDA (HR: 3.05, CI95%; from 1.14 to 8.15, p = 0.025). CONCLUSIONS: Endothelial dysfunction (sE-selectin and nitrates) and OxS (MDA) are independent indicators of a worse prognosis in COVID-19 patients requiring hospitalization.

Osteopontin's relationship with malnutrition and oxidative stress in adolescents. A pilot study.

Osteopontin (OPN) is a protein involved in inflammatory illnesses such as fibrosis and cancer; its overexpression in cardiovascular diseases promotes the biomineralization of blood vessels and other soft tissues. Moreover, there is an active component of oxidative stress related with those diseases. The present study relates serum OPN levels with nutritional condition and oxidative stress in a group of adolescents. Anthropometric measurements were performed, and fasting blood samples were analyzed to determine OPN concentrations, blood chemistry parameters (glucose, triglycerides, total cholesterol, urea, uric acid, and creatinine) and oxidative stress biomarkers (Paraoxonase-1, Glutathione S-Transferase, Catalase, NAD(P)H Quinone Oxidoreductase, free carbonyl groups and malondialdehyde). Adolescents were categorized according to body mass index (BMI) and metabolic syndrome (MetS) criteria. We found increased OPN serum concentrations in overweight and obese adolescents, as well as in adolescents with MetS. Rises in OPN correlated with arm circumference and biomarkers of lipid peroxidation; with regard to serum glucose there was a trend to positive correlation. Our results suggest that serum OPN is associated to nutritional status and could be considered as an early biomarker of low-grade inflammation and probably the early biomineralization of soft tissues in adolescence.

Acute kidney damage by PM2.5 exposure in a rat model.

PM2.5 exposure is associated with a glomerular filtration rate (GFR) reduction, and renal tissue damage. The goal of this study was demonstrate the acute effect of PM2.5 on the kidney. Male rats were acutely exposed to PM2.5 or filtered air. Blood pressure was mesure and early kidney biomarkers were evaluated in serum and urine samples, and also IL-1ß, IL-6 and TNFα were determined. Oxidative biomarkers, angiotensin/bradykinin-related proteins, KIM-1, IL-6 and histology were determined. Blood pressure, GFR, and early kidney damage biomarkers increase together with oxidative biomarkers and angiotensin/bradykinin endocrine-related proteins increased after exposure to PM2.5. Urinary IL-6 increased after exposure to PM2.5, whereas in kidney cortex decreased. Histological changes were observed and accompanied by the induction of KIM-1. Acute exposure to PM2.5 not decline kidney function. However, it can induce early kidney damage biomarkers, oxidative stress, inflammation and angiotensin mediators, which perhabs culminates in a lose of renal function.

Physiological Network From Anthropometric and Blood Test Biomarkers.

Currently, research in physiology focuses on molecular mechanisms underlying the functioning of living organisms. Reductionist strategies are used to decompose systems into their components and to measure changes of physiological variables between experimental conditions. However, how these isolated physiological variables translate into the emergence -and collapse- of biological functions of the organism as a whole is often a less tractable question. To generate a useful representation of physiology as a system, known and unknown interactions between heterogeneous physiological components must be taken into account. In this work we use a Complex Inference Networks approach to build physiological networks from biomarkers. We employ two unrelated databases to generate Spearman correlation matrices of 81 and 54 physiological variables, respectively, including endocrine, mechanic, biochemical, anthropometric, physiological, and cellular variables. From these correlation matrices we generated physiological networks by selecting a p-value threshold indicating statistically significant links. We compared the networks from both samples to show which features are robust and representative for physiology in health. We found that although network topology is sensitive to the p-value threshold, an optimal value may be defined by combining criteria of stability of topological features and network connectedness. Unsupervised community detection algorithms allowed to obtain functional clusters that correlate well with current medical knowledge. Finally, we describe the topology of the physiological networks, which lie between random and ordered structural features, and may reflect system robustness and adaptability. Modularity of physiological networks allows to explore functional clusters that are consistent even when considering different physiological variables. Altogether Complex Inference Networks from biomarkers provide an efficient implementation of a systems biology approach that is visually understandable and robust. We hypothesize that physiological networks allow to translate concepts such as homeostasis into quantifiable properties of biological systems useful for determination and quantification of health and disease.

Effect of in vivo exposure to ambient fine particles (PM2.5) on the density of dopamine D2-like receptors and dopamine-induced [35S]-GTPγS binding in rat prefrontal cortex and striatum membranes.

Male Sprague-Dawley rats (8-9 weeks-old) were exposed for three days (acute exposure) or eight weeks (subchronic exposure) to purified air or concentrated ambient fine particles, PM2.5 (≤2.5 µm; 15 to 18-fold of ambient air; 370-445 µg/m3). In membranes from rat prefrontal cortex (PFC) or striatum, the density and function of dopamine D2-like receptors (D2Rs) were assessed by [3H]-spiperone binding and dopamine-stimulated [35S]-GTPγS binding, respectively. Glial activation was evaluated by immunoperoxidase labeling of the glial fibrillary acidic protein (GFAP). In the PFC, no significant changes in D2R density or signaling were observed after the acute and subchronic exposure to PM2.5. In the striatum, acute exposure to PM2.5 decreased D2R density, with no effect on signaling efficacy, whereas subchronic exposure did not affect D2R density but reduced signaling efficacy. Both acute and subchronic exposure to PM2.5 induced reactive gliosis in the striatum but not in the PFC. These results indicate that exposure to PM2.5 induces astrocyte activation and alters striatal dopaminergic transmission.

The ADMA/DDAH/NO pathway in human vein endothelial cells exposed to arsenite.

Inorganic arsenic (iAs) exposure is related to cardiovascular disease, which is characterized by endothelial dysfunction and nitric oxide (NO) depletion. The mechanisms underlying NO depletion as related to iAs exposure are not fully understood. The endogenous inhibitor of nitric oxide synthase, asymmetric dimethylarginine (ADMA), might be a molecular target of iAs. ADMA concentrations are regulated by proteins involved in its synthesis (arginine methyl transferase 1 [PRMT-1]) and degradation (dimethylarginine dimethylaminohydrolase [DDAH]). Both, ADMA and NO are susceptible to oxidative stress. We aimed to determine the ADMA/DDAH/NO pathway in human vein endothelial cells (HUVEC-CS) exposed to arsenite. We exposed HUVEC-CS cells to 1, 2.5 and 5µM of arsenite for 24h. We proved that arsenite at 5µM was able to decrease NO levels with an associated increase in ADMA and depletion of l-arginine in HUVEC-CS cells. We also found a decrease in DDAH-1 protein expression with 5µM of arsenite compared to the control group. However, we did not observe significant differences in PRMT-1 protein expression at any of the concentrations of arsenite employed. Finally, arsenite (2.5 and 5µM) increased NADPH oxidase 4 protein levels compared with the control group. We conclude that ADMA, l-arginine and DDAH are involved in NO depletion produced by arsenite, and that the mechanism is related to oxidative stress.

El trabajador de salud y la consejería sobre el VIH y SIDA / The health care workers and the counseling about HIV and AIDS

En México, en diciembre de 1993, había más de 17 000 casos de SIDA declarados. Sin embargo, ciertas estimaciones indican que aproximadamente 100 000 individuos están infectados con el VIH. El ser seropositivo al VIH o padecer el SIDA, implica una gran carga emocional, por lo que apoyo psicosocial es crucial en este tipo de pacientes. En este documento se subraya la importancia de la consejería en el trabajo clínico y de salud pública en la batalla contra la epidemia de VIH y SIDA. Se presenta en forma resumida la experiencia sobre técnicas de consejería en la formación de 89 trabajadores de la salud (TDS), y se muestra la efectividad de la intervención educativa. Entre los hallazgos destaca el descubrimiento de actitudes homofóbicas entre estos profesionales, particularmente aquéllos sin experiencia previa en el manejo de pacientes infectados por el VIH. En el estudio se identificaron las necesidades educativas de los TDS. El número de casos estimados de infección por VIH y la tendencia de la epidemia ponen de manifiesto la necesidad de entrenamiento en consejería médica sobre VIH, pues más de 73 000 médicos en México habrán de enfrentar este problema en un futuro no muy lejano

By December 1993, more than 17 000 AIDS cases had been reported in Mexico and some estimates indicate approximately 100 000 individuals currently infected with HIV. From the patient's perspective, being HIV positive or having AIDS, places an enormous burden on psychosocial coping mechanisms. Thus, psychosocial support is required for all of these patients. This paper summarizes our educational intervention on counseling techniques and provides information of our demonstration project on the effectiveness of the educational intervention among 89 Mexican health care workers. Overall, these professionals showed improvement in their knowledge and goals of providing counseling. One of the more striking was the discovery of homophobic attitudes among them, particularly those with no previous experience in the care of HIV infected people. This exploratory study allowed us to identify research and educational needs of health care workers. The overwhelming number of estimated cases of HIV infections and the current trends of the epidemic reveal the necessity for training in medical counseling that over 73 000 physicians in Mexico will face in the immediate future.

Estudio seroepidemiológico de sarampión en Ciudad Nezahualcóyotl, México: una estrategia de evaluación / Sero-prevalence survey of measles antibody titers in children under 15 years of age in the city of Netzahualcoyotl, Mexico: an evaluation strategy

Introducción. Se propone una estrategia rápida de evaluación para determinar la proporción de niños menores de 15 años con anticuerpos a sarampión en un área urbana del Estado de México a través de estudios seroepidemiológicos y muestreo por conglomerados. Material y métodos. Se efectuó un estudio transversal que incluyó una encuesta serológica para determinar títulos de anticuerpos contra sarampión. Para la detección de IgG se utilizó la prueba de Elisa. Resultados. La encuesta serológica detectó que un 27.1 por ciento de los niños carecían de anticuerpos contra sarampión, siendo la proporción de niños protegidos del 72.9 por ciento. Los niños en los que se informó ausencia de vacunación presentaron mayor riesgo de ser seronegativos que los niños con antecedente de vacunación (razón de momios, RM, 2.9; intervalo de confianza, IC, 1.27-6.84). Se encontró que 22.6 por ciento de los niños vacunados con cartilla de vacunación no presentaron anticuerpos contra sarampión, siendo el grupo de edad de 1 a 4 años los más afectados con el 26.4 por ciento. Los niños vacunados en campaña mostraron un riesgo mayor de ser seronegativos que los vacunados en hospitales o centros de salud (RM=1.88, IC 0.72-5.20). Se detectó un 11 por ciento de niños con oportunidades perdidas durante el estudio. Conclusión. Se infiere que la seroconversión encontrada podría deberse a varias posibilidades: inadecuada técnica de aplicación del biológico, cadena de frío deficiente o factores de tipo biológico