Urinary Biomarker Levels Research Articles

Increased levels of renal damage biomarkers caused by excess exposure to trivalent chromium in workers in tanneries

BackgroundThe process for leather material production is carried out in developing countries using a large amount of trivalent chromium [Cr(III)]. Assesment of health risks for millions of workers in tanneries worldwide that are highly polluted with Cr(III) is needed. MethodsLevels of total Cr and its chemical species in wastewater samples from tannery built-up areas of Bangladesh were investigated. Cr-mediated renal damage was assessed in 100 male tannery workers by epidemiological analysis consisting of questionnaires and measurements of levels of urinary Cr and urinary renal damage markers [urinary levels of total protein and kidney injury molecule-1 (KIM-1)]. ResultsHigh levels of total Cr (mean ± standard deviation = 1,908,762 ± 703,450 μg/L) were detected in wastewater samples from 13 sites of tanneries. More than 99.99% of total Cr in the wastewater was Cr(III), indicating that workers in the tanneries were exposed to large concentrations of Cr(III). Cr levels (mean ± standard, 2.89 ± 4.23 μg/g creatinine) in urine samples from the workers in tanneries were >24-fold higher than the levels in a general population previously reported. Multivariate analysis showed significant correlations between urinary levels of Cr and urinary levels of renal damage biomarkers. Nagelkerke Pseudo R2 values also showed that Cr level is the strongest contributor to the levels of renal damage biomarkers in the workers. ConclusionOur results newly suggest that excess exposure to Cr(III) could be a risk for renal damage in humans.

Influence of pubertal development on urinary oxidative stress biomarkers in adolescent girls in the New York LEGACY cohort

Puberty is a time of intense growth and differentiation of breast tissue and a window of susceptibility (WOS) for breast cancer. Although oxidative stress markers have been associated with breast cancer risk, it is unclear whether oxidative stress levels are different during the pubertal WOS, and if so, whether these differences are related to breast cancer susceptibility. We measured urinary biomarkers of whole body oxidative stress (urinary F2-Isoprostanes and 8-oxodeoxyguanosine (8-oxodG)) in 158 girls (ages 6–13 years), 71 with and 87 without a breast cancer family history (BCFH) from a cohort of adolescent girls from the New York site of the LEGACY cohort (Lessons in Epidemiology and Genetics in Adults Cancer from Youth). We compared levels of urinary oxidative stress biomarkers (F2-Isoprostanes and 8-oxodG) across the pubertal window, defined by Tanner Stage (TS) of breast development, both cross-sectionally and longitudinally within girls over an 18-month follow up period. Urinary oxidative stress biomarkers were unrelated to pubertal stages in cross-sectional analyses after considering adjustments for body mass index (BMI) and BCFH. In our longitudinal analysis, we found that urinary 8-oxodG levels, but not F2-Isoprostane levels, increased with age in BCFH + girls (β = 6.12, 95% CI = 0.08–12.16) compared to BCFH-girls. Higher BMI was associated with higher level of F2-Isoprostane in both cross-sectional (β = 0.02, 95% CI = 0.0004–0.05) and longitudinal analysis (β = 0.02, 95% CI = 0.0002–0.05). These findings support that higher BMI increases oxidative stress biomarkers over the pubertal window and that there are changes in 8-oxodG oxidative stress biomarkers in girls with a BCFH compared to girls without a BCFH.

Ecological Momentary Assessment for the Evaluation of the Adherence to the Mediterranean Diet in the Context of Clinical Trials

Abstract Objectives The validation of tailored dietary Ecological Momentary Assessments (EMAs) to evaluate the continuous adherence to the Mediterranean Diet (MedDiet) for its use in the framework of nutritional intervention clinical studies. Methods We have developed a set of dietary mobile-app EMAs to evaluate the consumption of characteristics components key in the MedDiet. The EMAs will capture the frequency of consumption of the MedDiet products during a week and extract the rate of adherence to the MedDiet. A total of 100 healthy adults were enrolled on a trial to validate the use of EMAs as a novel screener of the MedDiet adherence. Participants received on their phone four randomized questions every day for 8 weeks. The questions were semi-qualitative and enquired for their intake diet on the last hours. The validity of the EMAs is compared with two validated questionnaires: Mediterranean Diet adherence screener (MEDAS) and a food frequency questionnaire (FFQ), both validated for the Spanish population. The levels of certain urinary dietetic biomarkers associated with the MedDiet was measured during the study. Tyrosol and hydroxytyrosol (two biomarkers of olive oil consumption) and alcohol biomarkers and free fatty acids were measured. Results A preliminary analysis of 21 subjects showed the capacity of EMAs to capture the adherence to the MedDiet, ranging in this population from 25–80% of adherence to the MedDiet recommendations. Scores obtained were correlated with the ones obtained in MEDAS, and the food frequencies captured in EMAs correlated with the frequencies reported in the FFQ at the end of the study. Individuals with higher scores in EMAs presented higher urinary levels of tyrosol and hydroxytyrosol. Participants reported a change in their dietary habits following their participation in the study, suggesting an additional beneficial effect of the EMAs. Conclusions The tailored EMAs are a reliable dietary assessment tool that provides an improved MedDiet adherence scoring while reducing participant's burden and capturing an accurate and continuous representation of the habitual dietary patterns. Moreover, they can be used to reinforce nutritional intervention and its sustainability. Funding Sources Alzheimer's Association and Instituto de Salud Carlos III of Spain.

Type 1 diabetes and hearing loss: Audiometric assessment and measurement of circulating levels of soluble receptor for advanced glycation end products.

We examined the hearing function in adults with and without type 1 diabetes (T1D) to investigate whether an association exists between hearing loss and duration of diabetes, haemoglobin A1C level, diabetes complications and levels of select serum and urinary biomarkers. We measured pure tone audiometry (PTA) thresholds; serum levels of C-reactive protein (CRP), vascular endothelial growth factor (VEGF), soluble receptors for advanced glycation end-product (sRAGE); and urinary isoprostane in 30 adults with T1D (age 43.8 ± 11.4 years). We also measured PTA thresholds in 11 adults without diabetes (age 53 ± 5.5 years). 63.3% of adults with T1D had high-frequency hearing loss. Among adults with T1D, those with hearing loss were older (48.2 vs 36.2 years old, P < .01), had a longer duration of diabetes (30.7 vs 21.2 years, P = .02), a greater prevalence of peripheral neuropathy (57.9 vs 9.1%, P = .02) and significantly lower median levels of sRAGE (1054.27 vs 1306.83 pg/mL, P = .03) compared to those with normal hearing. Adults with T1D between the ages of 40 and 60 years old, who had diabetes for ≥35 years, had significantly higher PTA thresholds at both 500and 8000 Hz than age-matched adults without diabetes. A significant proportion of adults with T1D have high-frequency hearing loss before age of 60 that is positively associated with age, duration of diabetes and presence of peripheral neuropathy. Our results are in support of previous studies suggesting a potential protective role of sRAGE against AGE toxicity and diabetes complications.

Impact of successful pediatric ureteropelvic junction obstruction surgery on urinary HIP/PAP and BD-1 levels

In the pediatric patient whose ureteropelvic junction obstruction (UPJO) is not always symptomatic, imaging is the most common means of detecting surgical success. There is interest, however, in other means of post-operative monitoring. A panel of antimicrobial peptides (AMPs) has been previously found to be elevated in UPJO, but the impact of surgical correction on these AMPs is unknown. To determine if elevated levels of candidate urinary AMP biomarkers of urinary tract obstruction decrease following UPJO repair. Pediatric patients undergoing surgical correction of an UPJO were recruited for participation. Bladder urine from uninfected consenting/assenting patients was collected immediately prior to surgery and then at least 6 months afterward. Based on prior studies demonstrating significant elevation of beta defensin 1 (BD-1), hepatocarcinoma-intestine-pancreas/pancreatitis-associated protein (HIP/PAP), cathelicidin (LL-37), and neutrophil gelatinase-associated lipocalin (NGAL) in patients with UPJO versus control patients, we performed enzyme-linked immunosorbent assays on these four AMPs to compare their expression before and after surgical intervention. If found to significantly decrease, AMP levels were compared to healthy controls. AMP levels were normalized to urine creatinine. Results were analyzed with paired t test or Wilcoxon test using Graphpad software. Correlation was calculated using Pearson or Spearman correlation. A p-value of <0.05 was considered significant. 13 UPJO patients were included in this study; 9 were male (69%). Age at surgery was a median of 4.3 years (average 6.1, range 0.4-18.4 years). Follow-up urine samples were collected a median of 27.4 months after surgery (average 27.4; range 7.8-45.3 months). All 13 patients had clinical improvement and/or signs of improved hydronephrosis on post-operative imaging. HIP/PAP and BD-1 significantly decreased in post-surgical samples compared to pre-surgical samples (p=0.02 and 0.01, respectively); NGAL and LL-37 did not significantly change. Overall, HIP/PAP decreased in 12 patients (92%) and BD-1 decreased in 11 patients (85%). BD-1 levels after successful repair were not different from healthy controls (p=0.06). Urinary biomarkers of obstruction should detect significant obstructive pathology as well as reflect its resolution. This would enable their use in post-operative monitoring and augment current methods of determining successful surgical outcome through imaging. The AMPs HIP/PAP and BD-1 are significantly elevated in UPJO but then significantly decrease after pyeloplasty, with BD-1 returning to healthy control levels. As a result, these AMPs could serve as markers of successful surgical intervention.

BIOLOGICAL MARKERS AND MORPHOGENESIS OF ACUTE RENAL INJURY IN RAT DICHLOROETHANE POISONING

The article presents the results of an experimental study on rat poisoning with 1,2-dichloroethane (250 µl / kg, intragastric administration). The aim of this work was to find the relationship between biological markers and morphological changes in acute damage to rat kidneys with dichloroethane. The study of urine samples of experimental animals by gas-liquid chromatography (GLC) revealed 1,2-dichloroethane in the concentration range of 0,05 – 0,90 µg / ml (95% C.I. = 0,09 – 0,90 µg / ml). Daily excretion with urine was 0,60 – 4,50 µg / 16h (95% C.I. = 1,14 – 3,93 µg / ml). Levels of nephron-specific biomarkers in urine were 194,62 ± 9,02 IU / L (NAGase, p = 0,0022) and 2,93 ± 0,38 ng / ml (KIM-1, p = 0,0022), which exceeded those in the control group by 5 and 23 times, respectively. Edema, disorders of intrarenal hemodynamics, leukocyte migration in interstitium, uneven damage to various areas of the kidneys due to adipose dystrophy and necrobiotic changes in the nephrothelium of the proximal tubules mainly in the cortical layer of the kidneys have developed in the kidneys. Positive correlations between the level of 1,2-dichloroethane in the urine and the level of KIM-1 (Spearman r = 0,7427, 95% C.I. 0,2764 – 0,9260, p = 0,0083), -N-acetylglucosaminidase (Spearman r = 0,8248, 95% C.I. 0,4613 – 0,9512, p = 0,0019), the scores on the EGTI scale (Spearman r = 0,8064, 95% C.I. 0,7126 – 0,8719, p &lt; 0.0001); the level of KIM-1 and the scores on the EGTI scale (Spearman r = 0,7427, 95% C.I. 0,2764 – 0,9260, p = 0.0083), -N-acetylglucosaminidase and the scores on the EGTI scale (Spearman R = 0,4684, 95% C.I. 0,2764 – 0,6244, p &lt; 0,0001), the level of the low and medium molecular weight substances in the blood and the scores on the EGTI scale (Spearman R = 0,6909, 95% C.I. 0,5549 – 0,7909, p &lt; 0,0001) were found.

Predisposición adquirida al daño renal asociada al consumo de tabaco

En los últimos años se ha visto una relación entre el tabaquismo y el daño renal. En cuanto al diagnóstico temprano del daño renal, nuestro grupo ha desarrollado el concepto de predisposición, aplicable al contexto de pacientes fumadores. Así, nuestra hipótesis es que el tabaco podría causar predisposición a sufrir daño renal agudo (DRA), lo que supondría que los fumadores podrían padecer DRA tras ser expuestos a alguna nefrotoxina, incluyendo dosis inferiores al límite tolerable. Nuestro objetivo es estudiar la relación entre los biomarcadores caracterizados en nuestro laboratorio: 1, 2 y 3 (BM1, BM2 y BM3) y el consumo de tabaco.Se tomaron muestras de orina de pacientes fumadores y no fumadores, sin daño renal ni exposición a factores de riesgo de este. Se midieron la cotinina (ELISA), la creatininuria (kit comercial) y los biomarcadores (western blot). La creatinina plasmática se obtuvo del historial clínico de los pacientes.Solo se vio una mayor excreción de BM3 en fumadores con respecto a no fumadores, aunque no se obtuvo una correlación con los niveles de cotinina (metabolito de nicotina que informa del grado de tabaquismo). A pesar de ello, BM3 podría suponer un buen biomarcador clínico para detectar la predisposición al DRA, lo que ayudaría a prevenir el daño renal en pacientes fumadores.

Biomarkers of Kidney Injury in Very-low-birth-weight Preterm Infants: Influence of Maternal and Neonatal Factors.

Acute kidney injury is an important cause of mortality in very-low-birth-weight (VLBW) preterm infants. As in the general population, the detection of renal damage cannot rely on the measurement of serum creatinine, since it has been demonstrated to be a weak predictor and a delayed indicator of kidney function deterioration. However, several candidate biomarkers have failed to prove sufficient specificity and sensitivity for a routine clinical use because of the poor awareness of their biological role. This study was aimed to investigate the impact of different maternal and neonatal conditions on several renal biomarkers in VLBW preterm infants during the first week of life. Preterm infants<32 weeks' gestation and <1500g were enrolled. We measured urinary biomarkers kidney injury molecule 1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), cystatin C, epidermal growth factor (EGF) and osteopontin (OPN) on the 1st, 3rd, and 7th day after birth. Thirty-tree infants were included. The multivariate analysis showed a significant association between gestational age, the presence of patent ductus arteriosus, antenatal maternal hypertension and the levels of urinary biomarkers. There is a possible relation between early biomarkers of renal injury and antenatal, perinatal and post-natal characteristics in VLBW preterm infants during the first week of life.

Comparison of the adverse renal effects of different types of NSAID based on COX inhibition in patients with headaches

Migraine is a common headache disorder that causes significant disabilities. Non-selective cyclooxygenase (COX) inhibitors (piroxicam, ketoprofen and ibuprofen) are most widely-prescribed NSAIDs treatment of headaches. Celecoxib is another NSAID therapy that has been approved in the last several years, with different mechanisms of action. The purpose of the study is to follow the renal function and comparisons of nephrotoxicity of different types of NSAID based on COX inhibition, in patients with cefalea-migraine that has been treated for a long period. Besides conventional markers of renal function (serum/urine creatinine determined by Jaffe's methods of enzymatic assay for urea in serum), we used nephelometry by β2 microglobulin (β2M) and photoelectric colorimetry for microalbuminuria in urine, to monitor glomerular and tubular functioning. Any history of kidney diseases was exclusion criteria to enter the study. The results show that the greatest deviations are observed in β2M in terms of its increase in all patients treated with piroxicam and ketoprofen, in 91.7% of the patients treated with ibuprofen, and in 50% of patients treated with celecoxib. The most frequent decrease was shown in creatinine values in urine, in 50% of the patients of piroxicam-treated group, 66.7% of the group treated with ketoprofen and ibuprofen, and 75% of the patients treated with celecoxib. Following the levels of specific biomarkers in urine we can recommend constant monitoring of renal functions during usage of different groups of NSAIDs and be careful while using analgesic-anti-inflammatory drugs. Keywords: adverse renal effects, non-steroidal anti-inflammatory drugs, migraine

Utility of urinary transferrin and ceruloplasmin in patients with systemic lupus erythematosus for differentiating patients with lupus nephritis.

Diagnosis of lupus nephritis (LN) is usually based on renal biopsy, which is an invasive technique that involves multiple risks. Therefore, different biomarkers have emerged as alternatives for the diagnosis of LN. Nonetheless, studies regarding urinary biomarkers in Latin American patients are limited. The objective of this study was to assess the diagnostic value of urinary transferrin and ceruloplasmin to differentiate patients who have renal involvement from those who do not. Systemic lupus erythematosus (SLE) patients that met the revised American College of Rheumatology (ACR) classification criteria were recruited. Patients with another autoimmune disease, active infection (urinary tract or systemic infection), renal replacement therapy, human immunodeficiency virus infection or pregnancy were excluded. A urine sample was collected from each patient. LN was diagnosed according to ACR criteria. The activity and chronicity of LN were measured using the Austin indices. Urinary transferrin and ceruloplasmin levels were measured using commercial enzyme-linked immunosorbent assay (ELISA) kits. Mann-Whitney U test and Student's t-test were used to compare data. Spearman's rank correlation was used to determine associations. Lastly, receiver operating characteristic (ROC) curves were created. The study involved 120 SLE patients. In all, 85% were female, 76% mestizo, the mean age was 32.8±12.1years and mean systemic lupus erythematosus disease activity index (SLEDAI) was 8.4±8.9; 64% had renal involvement. Urinary levels of the two biomarkers were significantly higher in patients with LN compared to those without LN. Similarly, urinary levels of both biomarkers were significantly higher in patients with active LN compared to those with inactive LN. Furthermore, urinary transferrin levels were significantly higher in Afro-Latin American patients. On the other hand, urinary transferrin levels correlated with SLEDAI and proteinuria, and transferrin and ceruloplasmin levels correlated with each other. The diagnostic value of ROC curves for these urinary biomarkers for LN were good. In our cohort of SLE patients, we found that transferrin and ceruloplasmin were potential biomarkers for LN, and can even differentiate active LN.

Urinary oxidative stress biomarker levels and reproductive outcomes among couples undergoing fertility treatments.

Are urinary levels of oxidative stress biomarkers associated with reproductive outcome success following fertility treatments? Levels of oxidative stress in the middle tertile for women are associated with the highest levels of reproductive success while no associations were noted for men. Oxidative stress may contribute to adverse fertility outcomes in the general population, but findings from couples undergoing fertility treatments are sparse. This prospective cohort study included 481 women and 249 of their male partners undergoing fertility treatments from 2007 to 2015, from the Environment and Reproductive Health (EARTH) study in Boston, MA. One urine sample per participant was collected at each cycle and analysed for two oxidative stress markers: 8-isoprostane-PGF2α (8-iso-PGF2α) and 8-isoprostane-PGF2α metabolite (F2-isoP-M). Reproductive outcomes were abstracted from medical records and included the fertilization rate, for IVF (oocytes fertilized/mature oocytes retrieved), and rates of implantation, clinical pregnancy and live birth, for both IVF and IUI. Cluster-weighted generalized estimating equations were used to analyse adjusted associations between exposure tertiles and outcomes. Levels of F2-isoP-M in the middle tertile were associated with the most success among women. Women in the upper tertile of F2-isoP-M had an adjusted mean live birth rate after IVF and IUI of 23% (95% CI: 17, 29) compared to 38% (95% CI: 31, 45) for women in the middle tertile and 27% (95% CI: 21, 34) in the lower tertile. The fertilization rate during IVF was higher for women with 8-iso-PGF2α in the middle tertile (0.77 [95% CI: 0.73, 0.80]) compared to women in the lower (0.69 [95% CI: 0.64, 0.73]) or upper tertiles (0.66 [95% CI: 0.61, 0.71]). No significant associations were found for other measured outcomes with 8-iso-PGF2α, or between any oxidative stress biomarker in men and reproductive outcomes in their partners. Isoprostanes are short-lived biomarkers and this study may not have captured the most relevant window of susceptibility for oxidative stress on the outcomes of interest. Findings from this study may not be generalizable to couples attempting conception without fertility assistance. This study suggests that a non-linear association may exist between oxidative stress and reproductive outcomes in a population undergoing fertility treatment, a finding not previously identified in the literature. Oxidative stress may represent the mechanism through which environmental chemicals are associated with adverse reproductive outcomes. This research was supported by the Intramural Research Program of the National Institutes of Environmental Health Sciences (NIEHS) (ZIA ES103314) and by NIEHS grants R01ES022955, R01ES009718 and R01ES00002. There are no competing interests to report. N/A.

Sustained Human Background Exposure to Acrolein Evidenced by Monitoring Urinary Exposure Biomarkers.

This study investigates a potential correlation between the intake of heat-processed food and the excretion of the acrolein (AC) biomarkers N-acetyl-S-(3-hydroxypropyl)-l-cysteine (HPMA) and N-acetyl-S-(carboxyethyl)-l-cysteine (CEMA) based on two human studies. Human exposure to AC is monitored using the AC-related mercapturic acids HPMA and CEMA in the urine of a) non-smoking volunteers under defined living conditions and b) of non-smoking volunteers on unrestricted or vegan diet under free living conditions. Free living volunteers in part show markedly enhanced urinary excretions of HPMA and CEMA. The intake of heat-processed food does not influence AC-related biomarker excretion. Incidentally enhanced urinary exposure biomarker levels appear to suggest AC exposure possibly from open fire, barbecuing, or tobacco smoke. However, kinetics of urinary biomarkers related to tobacco and other potential smoke exposure, do not correlate with those observed for HPMA and CEMA. This study is the first to convincingly show a sustained and substantial background exposure to AC in non-smoking humans, clearly independent from uptake of heat-processed foods. The data strongly point to endogenous AC generation by pathways of mammalian and/or microbial metabolism as yet not taken into consideration.

The urinary levels of CTX-II, C2C, PYD, and Helix-II increased among adults with KBD: a cross-sectional study

BackgroundKashin-Beck disease (KBD) is an endemic osteoarthropathy, and its pathogenesis is still not entirely clear. Pathologically, many KBD changes are similar to those of osteoarthritis (OA). Therefore, this study aimed to identify changes in the levels of potential urinary biomarkers for OA, including C-telopeptide of type II collagen (uCTX-II), type II collagen cleavage neoepitope (uC2C), pyridinoline (uPYD), and uHelix-II, among adults with KBD.MethodsUrinary samples of 83 external control (EC) subjects, 91 KBD patients, and 86 internal control (IC) subjects were tested by ELISA after the subjects completed a questionnaire and X-ray examination.ResultsThe medians of the four markers in the KBD group were higher than those in the EC group and those in the IC group. The medians in the grade II KBD group were higher than those in the grade I group but were not statistically significant (P = 0.301, P = 0.408, P = 0.204, and P = 0.898 for uCTX-II, uC2C, uPYD, and uHelix-II, respectively). The area under the curve (AUC) of uCTX-II (0.775) was higher than that of the others (0.672, 0.639, and 0.628 for uC2C, uPYD, and uHelix-II, respectively).ConclusionThe levels of uCTX-II, uC2C, uPYD, and uHelix-II were elevated in adults with KBD and showed an increasing trend as the severity of KBD increased. The prediction accuracy of uCTX-II was more useful than that of the others for assisting in the diagnosis of KBD.

Kidney injury biomarkers after cardiac angiography in children with congenital heart disease.

This study aims to investigate the changes in renal function and levels of urinary biomarkers before and after cardiac angiography in children with congenital heart disease (CHD). Children with CHD are at a risk for kidney injury during contrast exposure in cardiac angiography. We measured urinary protein, albumin, N-acetyl-β-D-glucosaminidase (NAG), β2-microglobulin (BMG), and liver-type fatty acid-binding protein (L-FABP) levels, as well as serum creatinine and cystatin C levels, before and after cardiac angiography in 33 children with CHD. No significant decrease was noted in either the creatinine-based or cystatin C-based estimated glomerular filtration rate at 24hours after angiography compared with that before angiography. Urinary protein, NAG, BMG, and L-FABP levels were significantly increased at 24hours after angiography, all of which returned to baseline levels at more than 7days after angiography. An increase in urinary level of protein, albumin, NAG, or BMG was mostly associated with increased urinary L-FABP level. An increase in both urinary BMG and L-FABP, but not that in urinary L-FABP alone, was associated with increased levels of urinary protein and NAG, as well as the greater dose of contrast media. Transient increases of kidney injury biomarkers following cardiac angiography are not necessarily associated with the impairment of renal function in a short time period; however, the increase in urinary protein, albumin, NAG, or BMG level may indicate greater stressesto the kidneys than the increase in urinary L-FABP alone in children with CHD.

Cardioprotective Effect of a Virgin Olive Oil Enriched with Bioactive Compounds in Spontaneously Hypertensive Rats.

Olive oil and its derivatives have been described to exert beneficial effects on hypertensive states and cardiovascular disease prevention. We studied the effects of chronic consumption of extra virgin olive oil (EVOO), enriched in bioactive compounds from olive fruit and leaves, on blood pressure, endothelial function, oxidative and inflammatory status, and circulating cholesterol levels, in spontaneously hypertensive rats (SHR). Thirty SHR were randomly assigned to three groups: a control untreated SHR group, an SHR group (1 mL/rat/day) of a control olive oil (17.6 mg/kg of phenolic compounds), and an SHR group (1 mL/rat/day) of the enriched EVOO (750 mg/kg of phenolic compounds) for eight weeks. Ten Wistar Kyoto rats (WKY) were included as healthy controls. Long-term administration of the enriched EVOO decreased systolic blood pressure and cardiac hypertrophy, and improved the ex vivo aortic endothelial dysfunction measured in SHR. Moreover, enriched oil supplementation reduced the plasma levels of Angiotensin II and total cholesterol, and the urinary levels of endothelin-1 and oxidative stress biomarkers, while pro-inflammatory cytokines were unaffected. In conclusion, sustained treatment with EVOO, enriched in bioactive compounds from the olive fruit and leaves, may be an effective tool for reducing blood pressure and cholesterol levels alone or in combination with pharmacological anti-hypertensive treatment.

Physiologically Based Kinetic Modeling-Facilitated Reverse Dosimetry to Predict In Vivo Red Blood Cell Acetylcholinesterase Inhibition Following Exposure to Chlorpyrifos in the Caucasian and Chinese Population.

Organophosphates have a long history of use as insecticides over the world. The aim of the present study was to investigate the interethnic differences in kinetics, biomarker formation, and in vivo red blood cell acetylcholinesterase inhibition of chlorpyrifos (CPF) in the Chinese and the Caucasian population. To this purpose, physiologically based kinetic models for CPF in both the Chinese and Caucasian population were developed, and used to study time- and dose-dependent interethnic variation in urinary biomarkers and to convert concentration-response curves for red blood cell acetylcholinesterase inhibition to in vivo dose-response curves in these 2 populations by reverse dosimetry. The results obtained revealed a marked interethnic difference in toxicokinetics of CPF, with lower urinary biomarker levels at similar dose levels and slower CPF bioactivation and faster chlorpyrifos-oxon detoxification in the Chinese compared with the Caucasian population, resulting in 5- to 6-fold higher CPF sensitivity of the Caucasian than the Chinese population. These differences might be related to variation in the frequency of single-nucleotide polymorphisms for the major biotransformation enzymes involved. To conclude, the interethnic variation in kinetics of CPF may affect both its biomarker-based exposure assessment and its toxicity and risk assessment and physiologically based kinetic modeling facilitates the characterization and quantification of these interethnic variations.

Application of Urinary Polyphenol Biomarkers Measured by Liquid Chromatography Tandem Mass Spectrometry to Assess Polyphenol Intake and Their Association with Overweight and Obesity in Free-Living Healthy Subjects

Although some polyphenol biomarkers in serum or urine have been identified by untargeted metabolomics and proved to reflect dietary polyphenol intake, only a few of them have been validated in different studies and populations with simple and reliable targeted methods. In the present study, a targeted metabolomics method by LC/MS/MS for the measurement of twenty-two polyphenol biomarkers in urine samples was established and validated to effectively assess the habitual polyphenol intake in free-living healthy Chinese subjects. Multivariate logistic regression models were used to assess relationships of biomarkers with overweight and obesity after adjusting for potential confounders. The levels of urinary polyphenol biomarkers, especially gut microbial metabolites of polyphenols, were inversely associated with overweight and obesity, and this association was more pronounced in the inflammatory groups, suggesting that it is of great importance to maintain polyphenol biomarkers at high levels or intake-sufficient polyphenols in obesity with chronic inflammation than others. The measurement of these biomarkers may offer a valid alternative or complementary addition to self-reported survey for the evaluation of polyphenol intake and investigation into their relationships with chronic disease-related endpoints in large-scale clinical and epidemiologic studies.

Utility of urinary transferrin and ceruloplasmin in patients with systemic lupus erythematosus for differentiating patients with lupus nephritis

Background and objectiveDiagnosis of lupus nephritis (LN) is usually based on renal biopsy, which is an invasive technique that involves multiple risks. Therefore, different biomarkers have emerged as alternatives for the diagnosis of LN. Nonetheless, studies regarding urinary biomarkers in Latin American patients are limited. The objective of this study was to assess the diagnostic value of urinary transferrin and ceruloplasmin to differentiate patients who have renal involvement from those who do not. Materials and methodsSystemic lupus erythematosus (SLE) patients that met the revised American College of Rheumatology (ACR) classification criteria were recruited. Patients with another autoimmune disease, active infection (urinary tract or systemic infection), renal replacement therapy, human immunodeficiency virus infection or pregnancy were excluded. A urine sample was collected from each patient. LN was diagnosed according to ACR criteria. The activity and chronicity of LN were measured using the Austin indices. Urinary transferrin and ceruloplasmin levels were measured using commercial enzyme-linked immunosorbent assay (ELISA) kits. Mann–Whitney U test and Student's t-test were used to compare data. Spearman's rank correlation was used to determine associations. Lastly, receiver operating characteristic (ROC) curves were created. ResultsThe study involved 120 SLE patients. In all, 85% were female, 76% mestizo, the mean age was 32.8±12.1years and mean systemic lupus erythematosus disease activity index (SLEDAI) was 8.4±8.9; 64% had renal involvement. Urinary levels of the two biomarkers were significantly higher in patients with LN compared to those without LN. Similarly, urinary levels of both biomarkers were significantly higher in patients with active LN compared to those with inactive LN. Furthermore, urinary transferrin levels were significantly higher in Afro-Latin American patients. On the other hand, urinary transferrin levels correlated with SLEDAI and proteinuria, and transferrin and ceruloplasmin levels correlated with each other. The diagnostic value of ROC curves for these urinary biomarkers for LN were good. ConclusionsIn our cohort of SLE patients, we found that transferrin and ceruloplasmin were potential biomarkers for LN, and can even differentiate active LN.

Pleiotropic association of LIPC variants with lipid and urinary 8-hydroxy deoxyguanosine levels in a Taiwanese population

BackgroundHepatic lipase (HL, encoded by LIPC) is a glycoprotein primarily synthesized and secreted by hepatocytes. Previous studies had demonstrated that HL is crucial for reverse cholesterol transport and affects the metabolism, composition, and level of several lipoproteins. In current study, we investigated the association of LIPC (Lipase C, Hepatic Type) variants with circulating and urinary biomarker levels by using subgroup and mediation analyses.MethodsA total of 572 participants from Taiwan were genotyped for three LIPC single nucleotide polymorphisms (SNPs) by using TaqMan assay. Fasting levels of glucose, lipid profile, inflammation markers, urine creatinine and 8-hydroxy deoxyguanosine (8-OHdG) were measured. The chi-square test, 2-sample t test and Analysis of variance (ANOVA) were used to examine differences among variables and genotype frequencies.ResultsSNPs rs2043085 and rs1532085 were significantly associated with urinary 8-OHdG levels, whereas all three SNPs were more significantly associated with Triglycerides (TG) or HDL-cholesterol (HDL-C) levels after additional adjustment for HDL-C or TG levels, respectively. Subgroup analyses revealed that the association of the LIPC SNPs with the levels of serum TG, HDL-C, and urinary 8-OHdG were predominantly observed in the men but not in the women. Differential associations of the LIPC SNPs with various lipid levels were observed in participants with different adiposity statuses. Mediation analyses indicated that TG levels acted as a suppressor masking the association of the LIPC genotypes with HDL-C levels, particularly in the men (Sobel test, all P < 0.01).ConclusionOur data revealed that interaction and suppression effects mediated the pleiotropic association of the LIPC variants. The effects of the LIPC SNPs depended on sex, adiposity status, and TG levels. Thus, our findings can provide a method for identifying high-risk populations of cardiovascular diseases for clinical diagnosis.

May 2019 at a glance: epidemiology, drug effects on biomarkers, adverse events with LVAD.

May 2019 at a glance: epidemiology, drug effects on biomarkers, adverse events with LVAD.