Placental Leucine Aminopeptidase as a Potential Specific Urine Biomarker for Invasive Ovarian Cancer

Background: A non-invasive and sensitive biomarker for the detection of ovarian cancer (OvCa) is lacking. We aim to investigate if urinary placental leucine aminopeptidase (P-LAP) can serve as a reliable biomarker for OvCa. Methods: P-LAP activity was measured using a LAP assay kit (Serotech Co., Ltd., Sapporo, Japan) in the urine of 22 patients with benign or borderline malignant ovarian tumors and 18 patients with OvCa. In this assay, L-methionine was added at 20 mM because P-LAP is functional, but other aminopeptidases are inhibited at this dose of L-methionine. Results: The mean urinary P-LAP activity was significantly higher in the OvCa group than in the benign or borderline malignant tumor group. When the cut-off value of P-LAP was determined as 11.00 U/L, its sensitivity and specificity for differentiating invasive cancer were 77.8% and 95.5%, respectively. Conclusion: Although the usefulness of this test should be confirmed in a larger cohort of cases and controls, our study is the first to highlight the importance of urinary P-LAP as a biomarker for OvCa.

Exposure to an Extended-Interval, High-Dose Gentamicin Regimen in the Neonatal Period Is Not Associated With Long-Term Nephrotoxicity

Objectives: To assess the association between gentamicin exposure and subclinical signs of nephrotoxicity in school children who were exposed to a high-dose gentamicin regimen in the neonatal period.Methods: Children receiving three or more doses (6 mg/kg) of gentamicin as neonates were invited to a follow-up in school age. We evaluated potential signs of subclinical nephrotoxicity with four validated urine biomarkers: protein-creatinine ratio (PCR), albumin-creatinine ratio (ACR), kidney injury molecule-1 (KIM-1), and N-acetyl-beta-D-glucosaminidase (NAG) normalized for urine creatinine (NAG-Cr). In addition, blood pressure was measured. The measures of gentamicin exposure were cumulative dose (mg/kg) and highest trough plasma concentration (TPC) in mg/L. We used logistic and linear regression and non-parametric kernel regression to analyze the relationship between gentamicin exposure and the urine biomarkers.Results: A total of 222 gentamicin exposed children were included. As neonates, the children were exposed to a median (interquartile range-IQR) cumulative gentamicin dose of 36 (26–42) mg/kg and the median (IQR) TPC was 1.0 (0.7–1.3) mg/L. At follow-up, 15 children (6.8%) had either one abnormal urine biomarker value (13 children) or two abnormal urine biomarker values (2 children). These 17 biomarker values were all marginally above the suggested upper cutoff, and included the following markers; KIM-1 (n = 2), NAC-Cr (n = 5), ACR (n = 6), and PCR (n = 4). All other 207 children had normal sets of all four urine biomarkers. One child had hypertension. There were no differences in gentamicin exposure, gestational age (GA) at birth or birth weight between the group of 15 children with one or two abnormal urine biomarker values compared to the other 207 children who had normal biomarker values. Using different regression analyses, we did not find any association between gentamicin exposure (cumulative dose and/or TPC) and the urine biomarker values.Conclusions: Exposure to an extended-interval, high-dose gentamicin regimen in the neonatal period was not associated with signs of subclinical nephrotoxicity in schoolchildren. We therefore suggest that the gentamicin treatment regimen evaluated in this study is safe in terms of long-term nephrotoxicity.Clinical Trial Registration:ClinicalTrials.gov, identifier: NCT03253614.

Assessment of aflatoxin exposure using urine biomarker in pregnant and non-pregnant women in Yazd, Center of Iran

Background: Aflatoxins (AFs) are one of the most prevalent toxins, which long-term exposure to them could be a risk factor for liver cancer. AFM1 is the hydroxylated metabolite of AFB1 , therefore, the presence of AFM1 in urine samples can give an appropriate estimation of dietary AF exposure in human. Methods: The present study aimed to evaluate the excretion level of AFM1 in urine samples of pregnant and non-pregnant women in Yazd, Iran. A total of 85 urine samples (42 pregnant and 43 non-pregnant) were selected randomly from women who had referred to health centers of Yazd during March to May 2017. From each participant, a 72-hour dietary recall was asked and the data were recorded and later analyzed by ELISA kits. Results: The results showed that the mean level of AFM1 in pregnant and non-pregnant women was 8.23±2.9 and 35.5±1.05 pg mL-1, respectively. Excretion of AFM1 in urine samples had a significant relationship with some demographic factors and type of consumed foods (P<0.05). Conclusion: There was a significant relationship between the education level, place of residence, and the consumption of nuts with the excretion of AFM1 . It can be concluded that some foods distributed in Yazd are contaminated with AFs, and a significant number of people are exposed to high concentrations of AFM1 .

Burkholderia Pseudomallei Short-Chain Dehydrogenase/ Oxidoreductase: Potential Urine Biomarker Candidate for Acute Melioidosis

INTRODUCTION: In the current climate of urgency in identifying biomarkers for the development of rapid diagnostic kits, the use of urine samples to diagnose acute melioidosis was evaluated, comparing urine samples from Burkholderia pseudomallei culture-positive and culture-negative patients, and comparing pneumonic and septicemic melioidosis. MATERIAL AND METHODS: Eleven urine samples from clinically suspected melioidosis patients from a tertiary referral center, Hospital Tengku Ampuan Afzan, Pahang was used. An in-solution method for the detection of bacterial proteins using liquid chromatography-mass spectrometry quadrupole time-of-flight (LCMS QTOF) was used. RESULTS: Three bacterial proteins were consistently detected among all the culture[1]positive and PCR-positive cases tested, namely SDR family NAD(P)-dependent oxidoreductase protein (32kDa), 3-hydroxyacyl-CoA dehydrogenase Burkholderia sp. (32kDa), and NAD(P)-dependent dehydrogenase (short-subunit alcohol dehydrogenase family) Burkholderia sp. (33kDa). CONCLUSIONS: Short-chain dehydrogenase (SDO) proteins could potentially be a urine biomarker candidate as these have shown to aid in the ability of Burkholderia spp. to invade host cells as this action is important for the initial intracellular survival of the organism.

Serum and Urine Biomarker Leucine-Rich Alpha-2 Glycoprotein 1 Differentiates Pediatric Acute Complicated and Uncomplicated Appendicitis

Purpose: This prospective, single-center cohort study analyzes the potential of inflammatory protein mediator leucine-rich alpha-2 glycoprotein 1 (LRG1) for the early and accurate diagnosis of acute appendicitis (AA), and differentiation of acute complicated (AcA) from uncomplicated appendicitis (AuA). Methods: Participants were divided into the AcA, AuA, and control groups, and their serum (s-LRG1) and urine LRG1 (u-LRG1) levels were assayed preoperatively on the second and fifth postoperative days. Results: 153 patients participated, 97 had AA. Preoperative u-LRG1 with a cut-off value of 0.18 μg/mL generated an area under the receiver operated characteristic (AUC) curve of 0.70 (95% CI 0.62–0.79) for AA versus control (p < 0.001), while the results for AcA versus AuA were not significant (AUC 0.60, 95% CI 0.49–0.71, p = 0.089). The s-LRG1 levels of AA versus the control with a cut-off value of 51.69 μg/mL generated an AUC of 0.94 (95% CI 0.91–0.99, p < 0.001). The cut-off value of s-LRG1 was 84.06 μg/mL for diagnosis of AcA from AuA, and therefore, significant (AUC 0.69, 95% CI 0.59–0.80, p = 0.001). Conclusions: LRG1 exhibited excellent diagnostic performance as an inexpensive, non-invasive, rapid, and accurate biomarker able to reflect the pathogenesis of AA. LRG1 has the potential to replace advanced imaging to diagnose clinically ambiguous AA cases.

Daily water regime and sample sampling affect Blood and Urine parameter value change in healthy individuals

Background: Blood and Urine biomarkers are indicators of the subject health status. Understanding the effect of pre-analytical factors is important for the data quality of bio-specimens. Water as a necessary element for the normal functioning of living beings and sampling frequency influences the homeostatic range of parameters. The study examines the effect of 9-days fluid intake and 2-time sampling on concentration changes of 7-Urine and 17-Blood variables. Material and Method: SPSS software v23.0 applies to data processing. The group of 23 healthy subjects divide based on water intake and gender. Results: A statistically significant difference(p<0.01) between 1st/2nd sampling is confirmed for Freezing point depression, Sodium, Potassium, Creatinine Urea and Urate in Urine, Urea, Urate, Glucose, Hematocrit, Thrombocyte in Blood. The difference between water intake after 1st sampling is confirmed (p<0.01) for Freezing point depression, Sodium, Urate and(p<0.05) for Potassium(p<0.05), Chloride(p<0.05), Creatinine(p<0.05), Urate, Urea in Urine and Potassium(p<0.01) and Chloride(p<0.05) in Blood. Difference between gender exists for Urea(p<0.05) in Urine after 2nd sampling and Urate(P<0.01), Glucose(p<0.01/0.05), Ht(p<0.01/0.05) after 1st and 2nd sampling and MCHC(p<0.01) after 2nd sampling in Blood samples. Conclusion: Water intake increases Blood and Urine biomarker range after sampling.

Association of Blood and Urine Parameter Value Change With the Amount of Consumed Water Regime and Sample Sampling in Healthy Individuals

Background: Understanding the effect of pre-analytical factors is important for data quality of bio-specimens and health status. The study examines the effect of 9-days fluid intake and 2-time sampling on concentration changes of 7-Urine and 17-Blood variables. Material and Method: SPSS software v23.0 applies to data processing. The group of 23 healthy subjects divide based on water intake and gender. Results: A statistically significant difference(p<0.01) between 1st/2nd sampling is confirmed for Freezing point depression, Sodium, Potassium, Creatinine Urea and Urate in Urine and Urea, Urate, Glucose, Hematocrit, Thrombocyte in Blood. The difference between water intake after 1st sampling is confirmed (p<0.01) for Freezing point depression, Sodium, Urate and(p<0.05) for Potassium(p<0.05), Chloride(p<0.05), Creatinine(p<0.05), Urate, Urea in Urine and Potassium(p<0.01) and Chloride(p<0.05) in Blood. Difference between gender exists for Urea(p<0.05) in Urine after 2nd sampling and Urate(P<0.01), Glucose(p<0.01/0.05), Ht(p<0.01/0.05) after 1st and 2nd sampling and MCHC(p<0.01) after 2nd sampling in Blood samples.Conclusion: Water intake increases blood and urine biomarker range after sampling.