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| Ammonia reabsorption by the thick ascending limb. Primary mechanism of apical ammonium absorption is via substitution of NH 4 1 for K 1 and transport by the loop diuretic-sensitive, apical NKCC2 transporter. Cytoplasmic NH 4 1 is transported across the basolateral

| Ammonia reabsorption by the thick ascending limb. Primary mechanism of apical ammonium absorption is via substitution of NH 4 1 for K 1 and transport by the loop diuretic-sensitive, apical NKCC2 transporter. Cytoplasmic NH 4 1 is transported across the basolateral

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Renal nitrogen metabolism primarily involves urea and ammonia metabolism, and is essential to normal health. Urea is the largest circulating pool of nitrogen, excluding nitrogen in circulating proteins, and its production changes in parallel to the degradation of dietary and endogenous proteins. In addition to serving as a way to excrete nitrogen,...

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... the loop of Henle, ammonia reabsorption occurs, with the major transport site being the medullary thick ascending limb. Ammonia is reabsorbed in the form of NH 4 1 primarily via the apical, loop diuretic-sensitive transporter, NKCC2 (Figure 9). Although other NH 4 1 transporters are present, their quantitative contribution is much less. ...

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... Even at such correlation strengths, HbA 1c is instrumental in determining the long-term clinical risks of fluctuating glucose levels [36]. It is likely that carbamylated proteins with long half-lives similarly better depict time-averaged urea exposure than single blood urea measurements which fluctuate significantly in relation to recent diet, hydration, volume, circulatory status, medications, acute GFR changes, and catabolic state [37,38]. Furthermore, carbamylation occurs through non-uremic processes (e.g., myeloperoxidase catalyzed oxidation of thiocyanate derived from diet and smoking) [15] and can be exacerbated by amino acid deficiencies from nutritional imbalance, protein-energy wasting, or other means [17]. ...
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Background Protein carbamylation, a post-translational protein modification primarily driven by urea, independently associates with adverse clinical outcomes in patients with CKD. Biomarkers used to quantify carbamylation burden have mainly included carbamylated albumin (C-Alb) and homocitrulline (HCit, carbamylated lysine). In this study, we aimed to compare the prognostic utility of these two markers in order to facilitate comparisons of existing studies employing either marker alone, and to inform future carbamylation studies. Methods Both serum C-Alb and free HCit levels were assayed from the same timepoint in 1632 individuals with CKD stages 2–4 enrolled in the prospective Chronic Renal Insufficiency Cohort (CRIC) study. Adjusted Cox proportional hazard models were used to assess risks for the outcomes of death (primary) and end stage kidney disease (ESKD) using each marker. C-statistics, net reclassification improvement, and integrated discrimination improvement were used to compare the prognostic value of each marker. Results Participant demographics included mean (SD) age 59 (11) years; 702 (43%) females; 700 (43%) white. C-Alb and HCit levels were positively correlated with one another (Pearson correlation coefficient 0.64). Higher C-Alb and HCit levels showed similar increased risk of death (e.g., the adjusted hazard ratio [HR] for death in the 4th carbamylation quartile compared to the 1st was 1.90 (95% confidence interval [CI] 1.35–2.66) for C-Alb, and 1.89 [1.27–2.81] for HCit; and on a continuous scale, the adjusted HR for death using C-Alb was 1.24 [1.11 to 1.39] per standard deviation increase, and 1.27 [1.10–1.46] using HCit). Both biomarkers also had similar HRs for ESKD. The C-statistics were similar when adding each carbamylation biomarker to base models (e.g., for mortality models, the C-statistic was 0.725 [0.707–0.743] with C-Alb and 0.725 [0.707–0.743] with HCit, both compared to a base model 0.723). Similarities were also observed for the net reclassification improvement and integrated discrimination improvement metrics. Conclusions C-Alb and HCit had similar performance across multiple prognostic assessments. The markers appear readily comparable in CKD epidemiological studies.
... In addition, it was previously reported that amino acid composition could affect the rate of protein degradation 29 ; therefore, the different compositions among the protein ingredients could also be a cause of this observation. Urea, one of the markers for protein degradation, could be found higher in concentration with high-protein diets and is toxic at high levels 30,31 . Therefore, a lower urea level from the CLHd could be bene cial to the dogs, especially those consuming higher levels of dietary protein. ...
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Research has shown various hydrolyzed proteins possessed beneficial physiological functions; however, the mechanism of how hydrolysates influence metabolism is unclear. Therefore, the current study aimed to examine the effects of different sources of protein hydrolysates, being the main dietary protein source in extruded diets, on metabolism in healthy adult dogs. Three complete and balanced extruded canine diets were formulated: control chicken meal diet ( CONd ), chicken liver and heart hydrolysate diet ( CLHd ), mechanically separated chicken hydrolysate diet ( CHd ). A replicated 3×5 Latin rectangle design was used with 10 adult beagles. Plasma and fresh fecal samples were collected at day 28. Samples were analyzed for global metabolomics with ultra-performance liquid chromatography and high-resolution mass spectrometer interfaced with a heated electrospray ionization source and mass analyzer. In general, there were lower concentrations of dipeptides and protein degradation metabolites, indicating higher protein digestibility, in dogs fed protein hydrolysate diets in contrast with CONd (q<0.05). Higher plasma pipecolate and glutamate, higher fecal spermidine and indole propionate, and lower phenol-derived products were found in CLHd group than CONd (q<0.05), indicating lower oxidative stress and inflammation levels. The main difference in lipid metabolism between CHd and CONd was the bile acid metabolism, showing lower circulating bile acid, lower unconjugated bile acid excretion and higher taurine-conjugated bile acid excretion in the CHd group (q<0.05).
... Notably, when creatinine concentrations surpass twice the standard value, it typically signifies a 50% reduction in GFR (Palmer et al. 2018). Either intensified protein breakdown or the conversion of ammonia to urea, stemming from the augmented activity of enzymes pivotal to urea synthesis, can cause a surge in blood urea nitrogen concentrations (Weiner et al. 2015). ...
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Hospitalized patients often develop acute renal failure (ARF), which causes severe morbidity and death. This research investigates the potential renoprotective benefits of sildenafil and furosemide in glycerol-induced ARF, and measures kidney function metrics in response to nanoparticle versions of these medications. Inducing ARF is commonly done by injecting 50% glycerol intramuscularly. Rats underwent a 24-h period of dehydration and starvation before slaughter for renal function testing. We investigated urine analysis, markers of oxidative stress, histology of kidney tissue, immunohistochemistry analysis of caspase-3 and interleukin-1 beta (IL-1 β), kidney injury molecule-1 (KIM-1), and neutrophil gelatinase–associated lipocalin (NGAL), which are specific indicators of kidney tissue damage. The results of our study showed that the combination of sildenafil and furosemide, using both traditional and nanoparticle formulations, had a greater protective effect on the kidneys compared to using either drug alone. The recovery of renal tissue indicators, serum markers, and urine markers, which are indicative of organ damage, provides evidence of improvement. This was also indicated by the reduction in KIM-1 and NGAL tubular expression. The immunohistochemistry tests showed that the combination therapy, especially with the nanoforms, greatly improved the damaged cellular changes in the kidneys, as shown by higher levels of caspase-3 and IL-1β. According to the findings, a glycerol-induced rat model demonstrates that sildenafil and furosemide, either alone or in combination, in conventional or nanoparticulate forms, improve ARF dysfunction. The synergistic nanoparticulate compositions show remarkable effectiveness. This observation highlights the possible therapeutic implications for ARF treatment.
... Urea is synthesized in the liver by protein catabolism and blood urea is filtered by the glomerulus and undergoes tubular reabsorption, so urea is directly related to nutritional status, protein metabolism and kidney condition. SARS-CoV-2 can activate the renin-angiotensin-aldosterone system causing renal vasoconstriction, decreased glomerular filtration and decreased urea excretion, increased absorption of water as well as sodium and passive reabsorption of urea (41,42). Since urea is the end product of protein metabolism, it can be used as a marker of kidney function. ...
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The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging crisis affecting the public health system. The clinical features of COVID-19 can range from an asymptomatic state to acute respiratory syndrome and multiple organ dysfunction. Although some hematological and biochemical parameters are altered during moderate and severe COVID-19, there is still a lack of tools to combine these parameters to predict the clinical outcome of a patient with COVID-19. Thus, this study aimed at employing hematological and biochemical parameters of patients diagnosed with COVID-19 in order to build machine learning algorithms for predicting COVID mortality or survival. Patients included in the study had a diagnosis of SARS-CoV-2 infection confirmed by RT-PCR and biochemical and hematological measurements were performed in three different time points upon hospital admission. Among the parameters evaluated, the ones that stand out the most are the important features of the T1 time point (urea, lymphocytes, glucose, basophils and age), which could be possible biomarkers for the severity of COVID-19 patients. This study shows that urea is the parameter that best classifies patient severity and rises over time, making it a crucial analyte to be used in machine learning algorithms to predict patient outcome. In this study optimal and medically interpretable machine learning algorithms for outcome prediction are presented for each time point. It was found that urea is the most paramount variable for outcome prediction over all three time points. However, the order of importance of other variables changes for each time point, demonstrating the importance of a dynamic approach for an effective patient’s outcome prediction. All in all, the use of machine learning algorithms can be a defining tool for laboratory monitoring and clinical outcome prediction, which may bring benefits to public health in future pandemics with newly emerging and reemerging SARS-CoV-2 variants of concern.
... The increase in ruminal NH 3 -N concentration could be attributed largely to the efficient breakdown of urea into ammonia (Weiner et al., 2015). ...
... Previous study demonstrated that higher BUN levels were associated with adverse outcomes (29). Conversely, we found that patients with lower BUN levels were at increased risk of mortality, this might be related to restriction of dietary protein intake resulted in a reductction of urea generation (30). Moreover, we found that patients with diabetes on PD were associated with higher all-cause and CVD mortality. ...
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Background Though the albumin-to-alkaline phosphatase ratio (AAPR) is used as a biomarker in various diseases, little is known about its effect on outcomes after peritoneal dialysis (PD). Methods This multicenter retrospective study comprised 357 incident PD patients stratified according to the AAPR. Propensity score matching (PSM) was performed to identify 85 patients for a well-matched comparison of all-cause and cardiovascular mortality. Using Cox regression, we performed univariate and multivariate analyses to investigate the prognostic value of the AAPR and established a Kaplan-Meier curve-predicted nomogram to estimate expected overall survival (OS). We assessed the predictive accuracy using the concordance index (c-index). Results We found that the optimal cut-off of the AAPR to predict mortality was 0.36. In the present cohort of patients undergoing PD, a low AAPR strongly correlated with worse OS. In the multivariate analysis, the AAPR was shown to be an independent marker predicting reduced OS both before [hazard ratio (HR) 1.68, 95% confidence interval (CI) 1.08–2.60, P = 0.020] and after PSM (HR 1.96, 95% CI 1.06–3.62, P = 0.020). We also observed significant differences in OS in several subgroups, but not the group of patients with comorbidities. A nomogram was established to predict overall survival, with a c-index for prediction accuracy was 0.71 after PSM. Conclusion AAPR has potential as an independent prognostic biomarker in patients undergoing PD.
... The intestinal presence of biochemical parameters such as urea, creatinine, total bilirubin, total cholesterol, uric acid, triglycerides, and gamma-glutamyl transferase (GGT) has been reported in dogs (Forster et al., 2018;Kilburn et al., 2020). These parameters are commonly measured in serum to evaluate the health condition of humans (Gazzola et al., 2004;Weiner et al., 2015) and the general well-being of domestic animals (Kozat & Sepehrizadeh, 2017). Enterocytes and gut bacteria have been found to collectively generate certain quantities of urea through their metabolic processes (Patra & Aschenbach, 2018). ...
... Urea levels were higher in dogs with diarrhoea than those without. Intestinal ureases catabolize the conversion of urea to ammonia (Weiner et al., 2015), a toxic gas whose accumulation alters intestinal homoeostasis by inducing pathological processes that culminate in decreased nutrient absorption, epithelial cell proliferation, and impaired gut barrier function in monogastric animals (Hailemariam et al., 2021). This could perhaps be the mechanism underlying the association between urea and acute diarrhoea. ...
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Diarrhoea, which is a clinical manifestation of various illnesses, is frequently observed in dogs. Regrettably, many dog owners find it difficult to provide comprehensive case histories, primarily because of limited interaction with their canine companions. This study aimed to evaluate the potential of faecal biochemical analytes in detecting and characterizing acute diarrhoea in dogs. Sixty-two domestic dogs were selected using the proportionate stratified sample technique. A structured questionnaire was used to collect demographic and clinical data. Faecal stool specimens from the dogs were obtained using the colon flush technique. The specimens were taken through biochemical analysis to determine urea, creatinine, total bilirubin, total cholesterol, triglycerides, gamma-glutamyl transferase and uric acid levels. Results showed a significant association between the diarrhoea status of the participants and their age, weight, breed, body size, source of last diet, period of inappetence, and other gastrointestinal signs (p < 0.050, respectively). Dogs that had not eaten in at least three days were five times more likely (p < 0.05) to have diarrhoea. Furthermore, miniature breeds were about six times more likely to develop diarrhoea (p < 0.05). Of the seven selected biochemical parameters, total faecal cholesterol was the most predictive index in diagnosing acute diarrhoea in dogs, with a likelihood ratio of 6.5, and it was the most accurate in predicting defecation stooling frequency and texture. In summary, in situations of inadequate case histories, measuring total faecal cholesterol could assist veterinarians in detecting diarrhoea and predicting its faecal stooling texture and frequency in dogs.
... In addition, renal ammonia excretion can also have a variable contribution to the urinary N balance. 35 Renal urea absorption along the nephron is mainly regulated by vasopressin and involves both, the activity of UT-A urea transporters encoded by SLC14A1 and the abundance of aquaporins (e.g. AQP3 and AQP7) in the plasma membrane of the inner medullary collecting duct. ...
... AQP3 and AQP7) in the plasma membrane of the inner medullary collecting duct. 35,36 The present analysis of renal gene expression revealed a numerically higher abundance of SLC14A1 (FC = 2.58, p = 0.114, HMUg < LMUg) and a significantly higher abundance of AQP3 (FC = 1.30, p = 0.003, HMUg < LMUg) in LMUg compared to HMUg, which might indicate an increased urea reabsorption into the interstitium in LMUg. In accordance, SLC38A2 (FC = 1.24, p = 0.029, HMUg < LMUg), which has recently been shown to protect the renal medulla under hyperosmotic concentrations during urine concentration, 37 was also found to be higher abundant in LMUg compared to HMUg. ...
Article
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Milk urea (MU) concentration is proposed as an indicator trait for breeding toward reduced nitrogen (N) emissions and leaching in dairy. We selected 20 German Holstein cows based on MU breeding values, with 10 cows each having low (LMUg) and high (HMUg) MU genetic predisposition. Using RNA-seq, we characterized these cows to unravel molecular pathways governing post-absorptive body N pools focusing on renal filtration and reabsorption of nitrogenous compounds, hepatic urea formation and mammary gland N excretion. While we observed minor adjustments in cellular energy metabolism in different tissues associated with different MU levels, no transcriptional differences in liver ammonia detoxification were detected, despite significant differences in MU between the groups. Differential expression of AQP3 and SLC38A2 in the kidney provides evidence for higher urea concentration in the collecting duct of LMU cows than HMU cows. The mammary gland exhibited the most significant differences, particularly in tricarboxylic acid (TCA) cycle genes, amino acid transport, tRNA binding, and casein synthesis. These findings suggest that selecting for lower MU could lead to altered urinary urea (UU) handling and changes in milk protein synthesis. However, given the genetic variability in N metabolism components, the long-term effectiveness of MU-based selection in reducing N emissions remains uncertain.
... Traditional medicines include practices, such as herbal medicine, ayurvedic medicine, unani medicine, acupuncture, as well as other medical knowledge and practices (not orthodox) all over the globe. Inappropriate use of traditional medicines or practices can have negative or Bando Christopher David, Jummai Adamu Tutuwa, Rejoice Habila Tadawus, Emmanuel Odiba Ogu, Daniel Ifraimu, Oche Gabriel Sunday, Polly Shingu Jesse, Tsoken Danji Agbu dangerous effects and so, further research is needed to ascertain the efficacy and safety of the medicinal plants used in traditional medicine system (David et al., 2014). Therefore, this study aimed at determining the effect of ethanolic stem extract of Nelsonia canescens on selected biochemical parameters in male wistar rats induced with Sodium arsenite. ...
... Urea is the main end product of protein catabolism. Amino acid deamination takes place in the liver, which is also the site of the urea cycle, where ammonia is converted into urea and excreted through urine (David et al., 2014). It represents 90% of the total urinary nitrogen excretion. ...
Article
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Medicinal plants are those that have curative qualities or have positive pharmacological effects on the human body. The effect of ethanolic stem extracts from Nelsonia canescens was studied in relation to Sodium arsenite-induced toxicity in wistar rats. Fresh stem extract of Nelsonia canescens were obtained behind rice mill area, Wukari, Taraba state and was shade dried at room temperature and was homogenized into powder and measured at 300g into 100ml of absolute ethanol for 72 hours. 15 healthy male rats of 70g to 90g weight were obtained from animal house Makurdi, Benue state. Animals from Group 1 were used as control. 5mg/kg body weight of Sodium arsenite was administered to Group 2 animals while animals in Groups 3, 4 and 5 were administered with Nelsonia canescens ethanolic stem extracts 50 mg/kg, 100mg/kg and 200 mg/kg as well. At the end of 3 weeks the animals were sacrificed and serum sample were collected and analysed using standard methods. The results indicate that, when compared to those who received Sodium arsenite, those who received ethanol stem extracts of Nelsonia canescens showed a comparatively considerable liver protection against Sodium arsenite -induced damage. The levels of biochemical parameters: Albumin, Total protein, Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Alkaline phosphatase (ALP), Total bilirubin, Urea, Creatinine of rats administered with Sodium arsenite only was also observed. The Nelsonia canescens extract’s activity at 200mg/kg bw (higher dose) give a reasonable decrease in the amount of these liver enzymes. Deducing from study results, it indicates that Nelsonia canescens leaf extracts could be an effective agent in Sodium arsenite mediated liver toxicity in adult wistar rats and drug development.
... There were no significant differences after 3h of feeding. the increased of rumen pH value due to degradation of urea by bacterial ureases and produced more ammonia to blood streem then recycled from liver to rumen as endogenous sources of urea with saliva, that leads to significant increase of rumen pH (28) and increasing levels of non protin nitrogen (NPN) with daily feeding reduces the cost feeding and profuce more N excretion (13). The effect of replacing treated and untreated corn impurities with urea on rumen ammonia nitrogen (mg/100 ml) ( Table 3) referred to increase ammonia nitrogen (P<0.05) for replacing 39% treated corn impurities with urea or T10 for all collected times (0, 3h and 6h) after feeding. ...
Research
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This study was aimed to determine the effect of replacing treated and untreated corn impurities with urea instead of wheat bran on rumen bacteria and fermentation of Awassi lambs. Five levels of treated and untreated corn impurities as 44:0%, 32:11%, 20:22%, 10:32% and 0:39% bran:impurities in a 2×5 factorial experiment/ Completely Randomized Design using forty lambs with an initial weight of 27.45 ± 2.16kg and 4-5 months old. Individual feeding was used for 70 days and rumen fluid was sampled at 0, 3, 6h after morning feeding. Results showed an increasing (p<0.05) rumen pH at zero time especially corn impurities treated with urea and increasing (p<0.05) rumen ammonia at zero time and 3h after feeding with highly significant (p<0.01) increased at 6h, and superiority increased of volatile fatty acids (VFA's) for urea treated corn impurities (P<0.05) at zero time and after 3h of feeding, similar results for rumen bacterial count at zero time, 3h and 6h after morning feeding for two dilutions × 10 7 and × 10 9 Cfu/ml for impurities treated with urea. In conclusion, it is possible to use corn impurities instead of wheat bran, preferably treated with urea for positive increase rumen fermentation and total bacterial count in sheep.