Urine Samples Research Articles

Further Investigation Into an Environmental Source for Aminorex.

In 2009, levamisole was identified as a source for several aminorex positives reported in postrace equine samples in Canada. Since then, unexplained detections of aminorex continue to be identified in equine samples where there is no evidence to link these detections to a levamisole administration. Previous studies identified a compound named barbarin in some species of plants from the Brassicaceae family and suggested that barbarin may be a possible precursor for aminorex. The objectives of this study were to (1) investigate the link between barbarin and aminorex and (2) identify other biomarkers of plant origin. Methods were developed and validated for the detection of aminorex, barbarin, glucobarbarin, and other associated compounds. Aminorex was administered to one horse, and barbarin was not detected in any plasma and urine samples. Barbarea stricta and Barbarea orthoceras were administered to two horses, and aminorex was detected in all plasma and urine samples collected. Barbarin was detected in some plasma but not in urine samples. Resedine was observed in retrospective examination of chromatograms of the plant material and from all plants postadministration plasma and urine samples from the two horses. Resedine was administered to one horse and was detected in plasma and urine samples, but aminorex was only detected in urine samples. These results provide evidence that resedine is an intermediary compound between barbarin and aminorex in horses and that resedine can be used as a biomarker to eliminate the reporting of aminorex positives originating from the ingestion of plants from the Brassicaceae family.

Evaluation of N-NOSE as a surveillance tool for recurrence in gastric and esophageal cancers: a prospective cohort study

ObjectiveEarly detection of recurrent gastric and esophageal cancers remains a critical challenge. Innovative and non-invasive cancer screening technologies, such as N-NOSE, can improve early detection. N-NOSE is a urine-based scent test that leverages the olfactory abilities of the nematode C. elegans. For the first time, this prospective study evaluates the efficacy of the N-NOSE chemotaxis index as a novel biomarker for postoperative surveillance and recurrence in patients with upper gastrointestinal cancers.MethodsA two-year prospective cohort study was conducted at The University of Tokyo Hospital, involving 40 patients with gastric and esophageal cancers. Urine samples were collected pre- and postoperatively and analysed using the N-NOSE technique.ResultsIn cases of recurrence with vascular invasion, the chemotaxis index at 100-fold urine dilution was significantly elevated compared to the non-recurrence group.ConclusionThis study suggests the potential of N-NOSE as an effective follow-up tool for patients with upper gastrointestinal cancer, particularly those with vascular invasion. While N-NOSE has been validated to distinguish between cancer and non-cancer, and its performance compared to traditional markers has been proven, it has not been studied for recurrence. Our data highlights, for the first time, the capability of N-NOSE in the surveillance of cancer recurrence.

Mediating role of immune cells in association between volatile organic compounds and periodontitis: NHANES 2011-2014.

The relationship between humans and volatile organic compounds (VOCs) is a persistent concern due to their widespread sources and high evaporation rates. However, there is currently limited direct evidence linking VOC exposure to the development of periodontitis. This cross-sectional study analyzed 1525 participants and 21 urinary VOCs in the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2014, aiming to investigate the relationship between periodontitis risk, assessed by attachment loss (AL) and probing depth (PD) and individual VOCs using logistic regression, quantile regression, and subgroup analysis. Weighted quantile sum analysis (WQS) and subgroup analysis were utilized to evaluate whether VOC mixtures were associated with periodontitis risk. Multiple linear regression models were used to examine the association between VOC co-exposure and peripheral immune cell counts. A mediation analysis was performed to evaluate whether peripheral immune cells are involved in the effect of VOC co-exposure on periodontitis prevalence. Urinary levels of 2-aminothiazoline-4-carboxylic acid, mandelic acid, and N-acetyl-S-(4-hydroxy-2-butenyl)-L-cysteine were positively associated with the risk of periodontitis after adjusting for all covariates. The WQS models demonstrated a positive correlation between the mixture of VOCs and the risk of periodontitis, wherein 2-aminothiazoline-4-carboxylic acid emerged as the most important contributor. The mediation analysis suggested that monocytes may play a role in the observed association between VOC co-exposure and the prevalence of periodontitis. Exposure to VOCs is associated with a greater prevalence of periodontitis. Monocytes' mediating role plays a crucial function in the association between the risk of periodontitis and co-exposure to VOCs. Volatile organic compounds (VOCs) are chemicals that evaporate quickly and are found all around us-from paints to cleaning products. Understanding how these compounds affect our health is crucial, especially regarding conditions like periodontitis, a common oral chronic inflammatory disease. In our study, we looked at urine samples from 1525 people who participated in a national health survey between 2011 and 2014 to find out if there is an association between VOC exposure and the risk of developing periodontitis. We found that certain chemicals in the urine, which show VOC exposure, were indeed associated with a greater risk of the disease. We further investigated the collective impact of these VOCs on the risk of periodontitis, revealing that certain chemicals exert a more significant influence than their counterparts. Additionally, our research hints at a potential role for monocytes in the interplay between VOCs and the risk of periodontitis. Our data suggest that exposure to VOCs could be associated with a greater likelihood of periodontitis, with monocytes potentially playing a role in this relationship. This study helps us better understand the potential health impacts of daily chemical exposure and underscores the importance of investigating further how our environment affects our health.

Response of human metabolism to ultra-low and high nicotine cigarettes based on urine metabolomics and bioinformatic analysis.

This study aimed to evaluate the metabolomic profiles of urine samples obtained from smokers who smoked cigarettes with low and high nicotine content. Three smokers participated in this study. They were given low-nicotine (LN) cigarettes, and urine was collected at the end of the third day for the LN group. After 1 week of not smoking, they were given high-nicotine (HN) cigarettes, and urine was collected for the HN group. Untargeted metabolomics and bioinformatic analysis methods were used for urine analysis. PCA showed a high degree of similarity between samples within the group and a large distance between samples between groups, indicating a significant difference between the two groups. A total of 1150 significantly differential metabolites were selected between the HN and LN groups, such as cotinine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol-N-glucuronide. Two-way hierarchical clustering analysis also suggested noticeable differences between the two comparison groups Enrichment analysis indicates that the differential metabolites between the two groups were mainly enriched in 19 pathways, such as the protein kinase G (cGMP)-protein kinase G (PKG) signaling pathway, adenosine monophosphate (AMP)-activated protein kinase signaling pathway, mammalian target of rapamycin signaling pathway, and Parkinson's disease. Cigarettes with different nicotine content may alter the metabolism of smokers. A total of 1150 significantly different metabolites were identified between the HN and LN groups, which were mainly enriched in ABC transporters, protein kinase G (cGMP)-protein kinase G (PKG) signaling pathway, caffeine metabolism, and arginine biosynthesis pathways.

Simultaneous Detection of Glucose and Acetoacetate in Artificial Urine Samples Using 3D-Connector Microfluidic Paper Based Analytical Devices

Diabetic patients sometimes experience both hyperglycemia and hyperketonemia simultaneously. This condition requires proper management of glucose and ketone body biomarkers. The fluctuating intensity of these biomarkers necessitates regular monitoring. This study aims to develop concept non-enzymatic measurement method by integrating µPADs (microfluidic paper-based analytical devices) for detecting glucose and acetoacetate in artificial urine samples. The method uses silver nanoparticle formation for glucose detection and Schiff base reaction as well as the Rothera test for acetoacetate detection. Optimal conditions found include the glucose detection zone with volume ratio of AgNO3 500 mM : starch 3% (w/v) (1 : 1), and the acetoacetate detection zone with glycine 900 mM in phosphate buffer pH 9.4. The artificial urine sample combination consists of glucose, acetoacetate, and acetone with volume ratio of (1 : 1 : 1). The 3D-Connector for glucose uses NaOH 10 M : starch 3% (w/v) with volume ratio of (1 : 3), while for acetoacetate, sodium nitroprusside 15% (w/w) in DMF 5% (v/v). Validity for glucose measurement shows linearity (R² = 0.9664), precision (RSD = 4.56%), accuracy (88.75 – 99.62%), LOD (1.61 mM), and LOQ (5.37 mM). Conversely, acetoacetate measurement shows linearity (R² = 0.9636), precision (RSD = 1.24%), accuracy (99.44 – 99.73%), LOD (1.41 mM), and LOQ (4.69 mM).

Effects of salt substitute on urinary electrolytes and blood pressure in a real-world setting—cohort study in Hunan, China

Background and aimsSalt substitute is considered an effective strategy to reduce sodium and increase potassium intake and thereby lower blood pressure in China, but its benefits and risks are uncertain in real-world data. This study is designed to compare the difference in the 1-year efficacy of salt substitute and salt restriction on urinary electrolytes and blood pressure.Methods and resultsA total of 2,929 and 2,071 participants with the 24-h estimated urinary sodium excretion (eUNaE) above 2.36 g/d using salt substitute (SS) and salt restriction (SR) strategies, respectively, were followed for 1 year. Salt substitute users were further divided by potassium chloride (KCl) content (13% vs 25%) and duration (9–11 vs 12 months). The 24-h eUNaE and estimated urinary potassium excretion (eUKE) levels were calculated using the Kawasaki formula from spot urine sample. The SS group (n = 1,897) had lower eUNaE (3.82 ± 1.03 vs 4.05 ± 1.01 g/day, p < 0.01) than the SR group (n = 1,897) after 1 year. Both 13 and 25% KCl substitutes reduced eUNaE versus restriction (p < 0.05). The SS group had a higher eUKE than the SR group (2.09 ± 0.43 vs 1.71 ± 0.62 g/day, p < 0.01). The eUKE was higher with 25% versus 13% KCl substitutes, while the Na/K was lower with 25% versus 13% KCl substitutes (p < 0.05). No significant blood pressure differences occurred between the SS and SR groups (p > 0.05), whereas 25% KCl exposure was related to a lower level of SBP, regardless of whether it was compared with SR or 13% KCl.ConclusionCompared with salt restriction, salt substitute results in more sodium reduction and greater potassium increase. In spite of this, it does not result in better control of blood pressure, especially for the group receiving 13% KCl.

Follow-Up of Infants With Congenital Cytomegalovirus Following Maternal Primary Infection in the First Trimester and Normal Fetal Brain Imaging at Midgestation.

To determine outcomes at birth and postnatal sequelae of congenital cytomegalovirus (cCMV) infection following maternal primary infection in the first trimester with normal fetal brain imaging at midgestation. A retrospective, single-center cohort study was conducted, including all cases of proven cCMV infection following maternal primary infection in the first trimester from 2014 until 2021 and normal fetal brain imaging before 22weeks of gestation. All pregnancies were followed according to our protocol, which offers amniocentesis at least 8weeks after the onset of infection, serial ultrasound scans, and a fetal MRI in the third trimester. No women received treatment with CMV hyperimmune globulin or Valacyclovir during pregnancy. Follow-up of newborns was obtained, and newborns were classified as symptomatic or asymptomatic at birth. Postnatal sequelae were evaluated, and cases with a follow-up period of less than 12months were excluded. We found 42 newborns with cCMV, confirmed at birth by PCR for the CMV genome in neonatal urine samples, and normal fetal brain imaging up to 22weeks of gestation. Extracerebral signs of infection were present in 3/42 fetuses at the second trimester ultrasound (20-22weeks of gestation). In the third trimester (28-32weeks of gestation), none showed abnormal brain sonographic findings, but four exhibited extracerebral signs of CMV infection. Among 42 newborns, 29 were classified as asymptomatic (29/42, 69.1%) and 13 as symptomatic at birth (13/42, 30.9%, 95%CI 17.6%-47.1%). Eight newborns had abnormal cranial ultrasound/MRI (8/42, 19%), one presented abnormal postnatal brain imaging associated with hearing loss and four had sensorineural hearing loss (SNHL) at initial assessment. All were treated with oral Valganciclovir. Four newborns with normal hearing at birth had delayed onset SNHL. One case of hearing loss improved after treatment and returned to normal hearing. At a median follow-up of 35months, 8 infants had hearing loss (8/42, 19%, 95%CI 8.6%-34.1%) and none presented with severe brain abnormalities. For infants with congenital CMV following untreated first trimester maternal primary infection, the absence of abnormal prenatal brain ultrasound findings at the mid-trimester morphology scan does not rule out the possibility of postnatal neuroimaging anomalies or the need for treatment after birth. However, no severe brain abnormalities were detected after birth in our cohort, and the only observed sequelae were sensorineural hearing loss.

Challenges in early diagnosis of methanol poisoning in the emergency room - A case report

Background. Methanol is a toxic alcohol that causes severe poisoning due to its metabolites — formic and lactic acid — which lead to metabolic acidosis with a high anion gap and toxic encephalopathy. The severity of clinical features typically manifests within 6 to 72 hours and may include seizures and altered mental status. Case report. We present the case of a 45-year-old patient, a chronic alcoholic with no significant medical history, who was admitted to the Emergency Department in a comatose state (Glasgow Coma Scale [GCS] 4), tachypneic, and following a seizure episode. The patient also had a history of a minor head trauma 24 hours prior. Laboratory results revealed severe metabolic acidosis with a high anion gap, hepatocellular injury, renal insufficiency, and elevated serum levels of amylase and lipase. Toxicology screening, including a urinary sample, ethanol measurement (0 mmol/L), and imaging (MRI), strongly suggested methanol poisoning as the likely diagnosis. The patient was transferred to the Intensive Care Unit, where hemodialysis was performed. Subsequent brain scans revealed typical methanol toxicity patterns, including symmetrical necrosis of the basal ganglia and gliosis of the occipital and optic nerves. These findings underscore the importance of not attributing a low GCS solely to ethanol abuse, highlighting the need for a broader differential diagnosis.

Antibiotic Residues in Cattle Reported to Be Raised Without Antibiotics.

In 2019, the U.S. Department of Agriculture's (USDA) Food Safety and Inspection Service (FSIS) provided revised guidance for labeling claims of "raised without antibiotics" (RWA) and similar terms for meat and poultry produced in the US. In 2022, Price et al. published a study reporting that 15% of RWA-labeled cattle contained antibiotic residues in urine samples. In 2023, the USDA embarked on the project reported herein to independently determine the extent of antibiotic drug residues present in kidney and liver tissues from slaughtered cattle purported to be RWA. In this study, FSIS inspectors randomly collected kidney and liver tissues from 189 RWA animals in 79 slaughter establishments across the US. The samples were monitored for 185 veterinary drugs multiple times by different means, including liquid-chromatography coupled with tandem mass spectrometry (LC-MS/MS) and quadrupole high-resolution MS with an orbital ion trap instrument (LC-Q/orbitrap). Samples from 37 animals (20%) met the analytical identification criteria for at least one antibiotic confirmed in at least two analyses. Multiple antibiotics were determined in 11 RWA animals. Macrolides (tulathromycin, tildipirosin, tilmicosin, and gamithromycin) were confirmed in 20 (11%) of the RWA animals. The ionophore, monensin, was also confirmed in tissues from 11 samples, with unconfirmed/partial identifications in 8 others. Tetracyclines were confirmed in samples from 12 animals, several of which were found to contain multiple antibiotic residues. One animal each was also found to be positive for sulfamethazine (a sulfonamide antibiotic) and metabolites of penicillin G (a β-lactam antibiotic). Although they are not antibiotics, two anthelmintics (fenbendazole and eprinomectin) were confirmed in tissues from 3 RWA animals. FSIS has informed the slaughter establishments with positive results and advised them to conduct a root cause analysis and implement corrective actions.

Urinary Metabolite Profiles of Participants with Overweight and Obesity Prescribed a Weight Loss High Fruit and Vegetable Diet: A Single Arm Intervention Study

Background/Objectives: Thus far, no studies have examined the relationship between fruit and vegetable (F and V) intake, urinary metabolite quantities, and weight change. Therefore, the aim of the current study was to explore changes in urinary metabolomic profiles during and after a 10-week weight loss intervention where participants were prescribed a high F and V diet (7 servings daily). Methods: Adults with overweight and obesity (n = 34) received medical nutrition therapy counselling to increase their F and V intakes to national targets (7 servings a day). Data collection included weight, dietary intake, and urine samples at baseline at week 2 and week 10. Urinary metabolite profiles were quantified using 1H NMR spectroscopy. Machine learning statistical approaches were employed to identify novel urine-based metabolite biomarkers associated with high F and V diet patterns at weeks 2 and 10. Metabolic changes appearing in urine in response to diet were quantified using Metabolite Set Enrichment Analysis (MSEA). Results: Energy intake was significantly lower (p = 0.02) at week 10 compared with baseline. Total F and V intake was significantly higher at week 2 and week 10 (p < 0.05). In total, 123 urinary metabolites were quantified. At week 10, 21 metabolites showed significant changes relative to baseline. Of these, 11 metabolites also significantly changed at week 2. These overlapping metabolites were acetic acid, dimethylamine, choline, fumaric acid, glutamic acid, L-tyrosine, histidine, succinic acid, uracil, histamine, and 2-hydroxyglutarate. Ridge Classifier and Linear Discriminant Analysis provided best prediction accuracy values of 0.96 when metabolite level of baseline was compared to week 10. Conclusions: Urinary metabolites quantified represent potential candidate biomarkers of high F and V intake, associated with a reduction in energy intake. Further studies are needed to validate these findings in larger population studies.

UPLC-MS/MS High-Risk Screening for Sphingolipidoses Using Dried Urine Spots

Background: Early detection of sphingolipidoses is crucial to prevent irreversible complications and improve patient outcomes. The use of urine samples dried on filter paper (DUS) is a non-invasive strategy that simplifies the collection, storage, and shipping of samples compared to using liquid urine specimens. Objectives: (1) Develop and validate a multiplex ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS) methodology using DUS to quantify twenty-one lysosphingolipids normalized to creatinine for eight different sphingolipidoses. (2) Establish normal reference values to evaluate the clinical utility of the methodology. Methods: Samples were eluted from a 5 cm filter paper disk (~1 mL of urine) and extracted on Oasis MCX solid-phase extraction cartridges prior to injection in the UPLC-MS/MS system. Results: Urinary lysosphingolipids were stable on DUS at −80 °C and −30 °C for 117 days, at 21.5 °C and 4 °C for at least 26 days, and at 35 °C for 3 days. Globotriaosylsphingosine, glucosylsphingosine, and their analogs were elevated in patients with Fabry disease and Gaucher disease, respectively, compared to controls (p-value < 0.0001). The analysis of related analog profiles suggests a better overall reliability in detecting patients early, especially for Fabry patients. Conclusions: This approach is feasible and might be useful for the early detection, monitoring, and follow-up of patients with sphingolipidoses.

Organophosphate flame retardants and their metabolites in paired dog food and urine: Pet exposure through food consumption.

Companion dogs are exposed to various chemicals. However, our understanding of the sources and pathways of chemical exposure in pets remains limited. In this study, we collected urine samples from 47 dogs and corresponding samples of the food they consumed to analyze the concentrations and dietary exposure to organophosphate flame retardants (OPFRs) and their metabolites (mOPFRs). Triphenyl phosphate (TPHP) and its metabolite, diphenyl phosphate (DHPH), were the predominant compounds detected in dog food and urine samples. The concentration of mOPFRs in urine decreased as body weight increased; however, neither sex nor age significantly influenced mOPFR levels in dog urine. The estimated daily intake of OPFRs (343 ng/kg bw/day) through food consumption (EDIfood) was comparable to the previously reported levels of polycyclic aromatic hydrocarbons (324 ng/kg bw/day) and higher than those of pesticides (214 ng/kg bw/day), parabens (120 ng/kg bw/day), and polychlorinated biphenyls (103 ng/kg bw/day). By calculating the ratio of EDIfood to the cumulative daily intake based on urinary mOPFR concentrations, it was found that dietary sources contributed to 66% of the total TPHP exposure in dogs. This finding was further supported by Spearman's correlation analysis between parent OPFR concentrations in dog food and mOPFR levels in urine (p < 0.01), indicating that dietary intake may be one of the most significant exposure pathways for OPFRs in dogs. To the best of our knowledge, this is the first study to investigate the levels of OPFR exposure in paired dog food and urine samples.

RENAL FUNCTION PARAMETERS OF HEALTHY CAPTIVE AND SEMICAPTIVE AMAZONIAN MANATEES (TRICHECHUS INUNGUIS).

Evaluating renal function is essential for managing captive wild animals, particularly threatened species like the Amazonian manatee (Trichechus inunguis) in rehabilitation and prerelease programs. A series of urine diagnostic tests, such as gross appearance, semiquantitative chemical analyses, microscopic review of sediments, and quantitative analyses of urea and creatinine, were performed in 57 free-catch urine samples. On the same occasion, 52 serum samples from the same individuals were analyzed for creatine kinase activity, creatinine, blood urea nitrogen, albumin, sodium, potassium, and chloride concentrations; serum symmetric dimethylarginine (SDMA) was measured for the first time in the species. Females had higher urine creatinine concentration (21.7 ± 11.8 mg/dl) and specific gravity (1.003 ± 0.003 mg/dl) than males (11.9 ± 8.5 mg/dl and 1.001 ± 0.002 mg/dl) (P < 0.01 for both). Males presented higher urine creatinine:urea ratio than females (24.8 ± 29.2 and 20.5 ± 29.2, respectively) (P < 0.05). Urine pH was lower in manatees from the semicaptive area (7.8 ± 0.6) than in manatees under human care (8.5 ± 0.6) (P = 0.02) using the benchtop pH meter but showed no difference between areas in the dipstick reaction (P = 0.71), given its lower sensitivity and narrower range detection. Furthermore, 18 and 75% of urine samples were positive for the presence of blood and/or nitrite, respectively, in the dipstick reaction, possibly because of sample contamination. Significant correlation was observed between serum blood urea nitrogen and urine urea concentrations (P = 0.02), and between serum and urine creatinine concentrations (P = 0.01). Serum SDMA did not differ between sex or between captive and semicaptive individuals. However, it positively correlated with urine (P = 0.02) and serum creatinine (P = 0.01) demonstrating its potential as a bioindicator of kidney function. The renal function of Amazonian manatees can be effectively assessed by urinalysis, especially when combined with serum biochemistry.

The Green Heart Project: Objectives, Design, and Methods.

The Green Heart Project is a controlled, community-based clinical trial to evaluate the effects of increasing greenery on community health. The study was initiated in 2018 in a low-to-middle-income residential area of nearly 30,000 racially diverse residents in Louisville, KY. Community engagement was maintained throughout the project, with feedback integrated into its design and implementation. Based on land use, demographics, and greenness in the area, we designated 8 paired clusters of demographically- and environmentally matched "target" (T) and adjacent "control" (C) areas (total of 16 clusters). Levels of ultrafine particles, ozone, and nitrogen oxides were measured in each cluster. In-person exams were conducted for 735 participants in Wave 1 (2018-2019) and 545 participants in Wave 2 (2021). Blood, urine, nail, and hair samples were collected to evaluate cardiovascular risk, inflammation, stress, and pollutant exposure. Demographic and psychosocial data were collected as well. Cardiovascular function was assessed by measuring arterial stiffness and flow-mediated dilation. After Wave 2, more than 8,000 mature, mostly evergreen, trees and shrubs were planted in the T clusters. Post planting data were collected during Wave 3 (2022) from 561 participants. We plan to follow changes in area characteristics and participant health to evaluate the long-term impact of the greening intervention.

Epidemiology, microbiological profile and susceptibility pattern of uropathogens from a tertiary care hospital in central India

Urinary tract infections (UTIs) are the second most common infection in the community, whereas in hospitals, they are the most common healthcare-associated infections. Monitoring factors like the most common causative organisms and their susceptibility pattern is essential for tailored management and practicing antimicrobial stewardship. This study was done to determine the epidemiology, microbiological profile, and susceptibility pattern of uropathogens to make better antibiotic policy.: This was a retrospective descriptive study done at the Department of Microbiology, Pt. JNM Medical College, Raipur, Chhattisgarh in which analysis of the culture isolates obtained from urine samples received between January 2022 to December 2022 was performed.: Out of 2893 urine samples, 784 (27.1%) showed significant growth on culture. Females were more affected than males with male to female ratio being 1:2.3. Most common causative organism found in our study was (41.9%) followed by species (23.9%), non-albicans species(11.09%) and (10.3%). isolates showed 100% susceptibility to fosfomycin; 93% for nitrofurantoin, and 93% for carbapenems. In the case of isolates of the susceptibility percentage for nitrofurantoin and carbapenems were 59% and 82% respectively. In isolates were 100% susceptible to Teicoplanin and Fosfomycin, 82% for Nitrofurantoin.: followed by species the most common uropathogen. Nitrofurantoin and Fosfomycin were the most effective antibiotics against uropathogens.

Absorption, metabolism, and excretion of oral [14C] radiolabeled donafenib: an open-label, phase I, single-dose study in humans.

The study aims to investigate the absorption, metabolism, and excretion of donafenib, a deuterated derivative of sorafenib, in healthy Chinese male volunteers. Six healthy Chinese male volunteers were administered a single oral dose of 300mg donafenib containing 120 µCi of [14C]-donafenib. The study involved collecting and analyzing plasma, urine, and feces samples to determine the recovery and distribution of total radioactivity, identify metabolites, and assess the metabolic pathways of donafenib. The mean recovery of total radioactivity was 97.31% of the administered dose. Six metabolites were identified, with the parent drug being the major radioactive component in plasma (67.52% of total radioactivity) and feces (83.17% of the dose). The N-oxidation metabolite (M2) was prominent in plasma. Donafenib was predominantly excreted via feces, indicating liver metabolism, with minimal renal excretion. The metabolic pathways of donafenib were similar to those of sorafenib, but the metabolite profiles differed significantly. Notably, the amide hydrolysis metabolite M6, present in sorafenib, was absent in donafenib. Donafenib is primarily metabolized in the liver and excreted through feces, with a metabolic profile that differs from sorafenib due to the deuterium isotope effect. These differences in metabolic characteristics may contribute to donafenib's improved safety and efficacy as a treatment for advanced hepatocellular carcinoma (HCC).

Prediction of Possible Adverse Effects of Gestational Diabetes Mellitus on Maternal and Fetal Glomeruli by Urine and Amniotic Fluid Podocyte Degradation Products

Objectives: To compare the levels of podocyte damage markers nephrin and podocalyxin in urine samples taken at the time of gestational diabetes mellitus (GDM) diagnosis and at birth. Amniotic fluid podocalyxin (pdx) and nephrin levels were also analyzed to determine whether GDM had an impact on fetal glomeruli. Methods: A total of 50 patients, including 24 patients diagnosed with gestational diabetes and 26 healthy pregnant women whose gestational weeks were matched, were included in the study. GDM was diagnosed with a 75 g oral glucose tolerance test (OGTT). Fresh morning urine samples from patients diagnosed with GDM were collected. The second urine sample was collected with the help of a catheter during birth. Amniotic fluid samples were taken from patients who gave birth by cesarean section. The urinary podocalyxin and nephrin levels were measured via the quantitative sandwich enzyme immunoassay. Albumin–creatinine ratio (uACR) was also calculated in urine samples. Results: Urinary nephrin and pdx levels on the day of GDM diagnosis were similar in the GDM and control groups. Microalbuminuria was detected in only one patient from each group at the time of GDM diagnosis. In the urine samples taken from the time of birth, pdx and nephrin levels of the GDM group were significantly higher than the control group (p &lt; 0.001 for each). While microalbuminuria was detected in five patients (20.8%) at the time of birth in the GDM group, it was detected in only two patients (7.7%) in the control group. In the GDM group, a significant increase was detected between the urine pdx and nephrin levels measured at diagnosis and those measured at birth. In the control group, measurements at baseline and at birth were similar. There was no significant difference between the GDM and control groups in terms of amniotic fluid pdx and nephrin levels. A positive and significant correlation was detected between urinary pdx, nephrin, SBP, and uACR. Conclusions: While GDM triggers podocyte damage in maternal glomeruli, it does not cause significant change in fetal glomeruli.

Analysis of urine pH and specific gravity in pasture sheep

AbstractUrine pH and specific gravity represent the routine objectively verifiable parameters in urinalysis. Urinalysis is presently an underutilised analytical tool in ovine medicine but holds the same potential for predictive, diagnostic and prognostic use in sheep as it does in human and small animal medicine. Urine pH and specific gravity were measured as a health screening tool to ascertain normal physiological ranges in sheep on free-range summer pastures with free access to drinking water. Both sexes, different ages and various breeds including Dorper, Karakul, Damara and cross-breeds were recruited into the study to investigate possible sources of variation. Experimental animals were selected through stratified random sampling using farm records from a population of 69 rams, 135 ewes and 115 lambs. Samples of urine were collected from 60 rams, 60 ewes and 60 lambs by free catch following induction of micturition by transient apnoea. Urine pH was measured by a pH metre whilst urine specific gravity was evaluated with an optical refractometer. The urine pH ranged from 6.81 to 9.08, with a mean of 8.52 ± 0.02 (se). Only one animal had a urine pH value below the existing reference level (7.4–8.5). Concurrent abnormalities of the urine in dipstick analysis included proteinuria and glucosuria. Urine specific gravity varied from 1.003 to 1.050 with a mean of 1.021 ± 0.001 (se). Four sheep, all of them lambs, had urine-specific gravity values above the existing reference level (1.015 to 1.045). The high urine specific gravity was associated with diverse pathological findings including proteinuria, pyuria and glucosuria as well as the presence of urine sediment. Urine pH was influenced by gender and breed and specific gravity by age. The results affirmed that sheep naturally produce alkaline urine and aciduria points to an underlying pathological problem. An association between high urine specific gravity and systemic/urinary system disorders was evident in lambs. Isosthenuria and hyposthenuria were frequently encountered in healthy adult sheep and were considered indices of positive water balance rather than renal dysfunction. Collated data confirmed existing reference levels but revised the upper limit of normal urine pH to 9 instead of 8.5, and the lower limit of normal urine specific gravity to 1.003 instead of 1.015.

The Survey of Neonates in Pomerania: Design, Recruitment and Follow-Up of the Second Cohort, 2013-2017.

The Survey of Neonates in Pomerania (SNiP) is a birth cohort study conducted in Western Pomerania, Germany. SNiP-I recruited participants at birth between the years 2002 and 2008 (5801 inclusions). Since SNiP-I, population sociodemographic characteristics and the prevalence of early exposures, including overweight and gestational diabetes (GDM), have changed. To establish a second birth cohort (SNiP-II) in the same study area as the first population sample (SNiP-I) a decade later to investigate changes to early life exposures. Mothers with registered principal residence in the defined study area. Prospective, population-based, birth cohort study. The baseline survey of SNiP-II was conducted at birth between 2013 and 2017. The SNiP-I data set, on medical, epidemiological and socioeconomic data, associated health risk factors and the living conditions of newborns and their parents, and collection and storage of biomaterials, was improved and supplemented with additional data, including fetal growth parameters, urine samples,and maternal DNA. A follow-up survey of SNiP-II of children and their parents was conducted using questionnaires at 5-6 years of age. In a subgroup, an additional 2-h follow-up with clinical testing was performed by the German Neonatal Network (GNN). The baseline survey database includes 3502 mother-infant pairs, and 1194 (34%) participated in the SNiP-II follow-up study, with 401 in the clinical sub-study by GNN. Mothers in SNiP-II were older, more likely to have GDM and to be overweight, had better SES and smoked less during pregnancy than mothers in SNiP-I. Newborns in SNiP-II were less likely to be hospitalised than those in SNiP-I. Compared with SNiP-I, SNiP-II documents changes in the prevalence of early exposures during the prenatal and perinatal period. Using data from these prospective birth cohorts provides an opportunity to address research questions on how changes in exposures during pregnancy affect maternal and neonatal outcomes.

Chenopodium botrys Extract Affects Acute Kidney Injury Caused by Rhabdomyolysis in Rats Through TNF/NF‐κB Signaling Pathway

ABSTRACTDue to the anti‐inflammatory and antioxidant properties of the Chenopodium botrys and the pathological mechanisms of rhabdomyolysis in the kidney, this plant can be used to improve the symptoms of this disease. Then, in this study, we investigated the effects of this herb in improving kidney injury by rhabdomyolysis. Animals were divided into five groups: control, glycerol (received it for rhabdomyolysis induction), extract (received 12 mg/kg C. botrys extract), and treatment groups with dexamethasone (0.03 mg/kg) and extract (12 mg/kg). The extract was analyzed using HNMR. After a week, blood and urine samples were taken to measure protein, urea, and creatinine. Then, the animals were sacrificed, and the kidney tissue was removed to examine the antioxidant, TNF‐α, and histopathological evaluations. Also, NF‐κB gene expression was investigated. The serum creatinine, TNF‐α, and NF‐κB ratio significantly increased and antioxidant capacity decreased in the glycerol group compared with the control. Pathological evaluation also showed severe renal damage based on the related criteria. In the treatment groups with dexamethasone and especially extract, the considered parameters attenuated relatively compared with the glycerol group. Kidney damage and functional impairment associated with rhabdomyolysis, as well as the inflammatory response caused by increased NF‐κB and the proinflammatory cytokine TNF‐α, may be alleviated by C. botrys. Consequently, C. botrys could represent a potential therapeutic approach for patients with rhabdomyolysis‐induced acute kidney injury.