Co-ingestion of methanol and nitromethane: using falsely elevated creatinine as indicator for methanol antidote use.

PubMed

Leonard, Charlene P; Akhtar, Javed

2007-07-01

To report a case of co-ingestion of methanol and nitromethane in a child in order to heighten the awareness of false elevation of serum creatinine from nitromethane ingestion. Case report. Pediatric intensive care unit. A 4-yr-old previously healthy girl ingested an unknown quantity of "Blue Thunder" model-engine fuel, which consisted of methanol and nitromethane. The patient was treated with fomepizole for methanol ingestion using elevated creatinine level as a reason for treatment. The patient was asymptomatic but her creatinine level increased ten-fold (from 0.4 mg/dL to 4 mg/dL) within 6 hrs. Blood urea nitrogen, anion gap, and osmolar gap remained within normal limits. When the serum creatinine level was measured with enzymatic method instead of Jaffe's method, a normal creatinine level was obtained. The falsely elevated creatinine level was due to nitromethane. The falsely elevated serum creatinine levels due to nitromethane ingestion can lead to unnecessary therapeutic interventions. We intend to heighten awareness of this potential misstep by reporting this case.

Urea impairs β cell glycolysis and insulin secretion in chronic kidney disease

PubMed Central

Koppe, Laetitia; Nyam, Elsa; Vivot, Kevin; Manning Fox, Jocelyn E.; Dai, Xiao-Qing; Nguyen, Bich N.; Attané, Camille; Moullé, Valentine S.; MacDonald, Patrick E.; Ghislain, Julien

2016-01-01

Disorders of glucose homeostasis are common in chronic kidney disease (CKD) and are associated with increased mortality, but the mechanisms of impaired insulin secretion in this disease remain unclear. Here, we tested the hypothesis that defective insulin secretion in CKD is caused by a direct effect of urea on pancreatic β cells. In a murine model in which CKD is induced by 5/6 nephrectomy (CKD mice), we observed defects in glucose-stimulated insulin secretion in vivo and in isolated islets. Similarly, insulin secretion was impaired in normal mouse and human islets that were cultured with disease-relevant concentrations of urea and in islets from normal mice treated orally with urea for 3 weeks. In CKD mouse islets as well as urea-exposed normal islets, we observed an increase in oxidative stress and protein O-GlcNAcylation. Protein O-GlcNAcylation was also observed in pancreatic sections from CKD patients. Impairment of insulin secretion in both CKD mouse and urea-exposed islets was associated with reduced glucose utilization and activity of phosphofructokinase 1 (PFK-1), which could be reversed by inhibiting O-GlcNAcylation. Inhibition of O-GlcNAcylation also restored insulin secretion in both mouse models. These results suggest that insulin secretory defects associated with CKD arise from elevated circulating levels of urea that increase islet protein O-GlcNAcylation and impair glycolysis. PMID:27525435

Role of rumen butyrate in regulation of nitrogen utilization and urea nitrogen kinetics in growing sheep

USDA-ARS?s Scientific Manuscript database

Butyrate, a major rumen VFA, has been indirectly linked to enhancement of urea recycling based on increased expression of urea transporter (UT-B) in the rumen epithelia of steers fed a rumen butyrate-enhancing diet. Two studies were conducted to quantify the effect of elevated rumen butyrate concent...

Urea-induced ROS generation causes insulin resistance in mice with chronic renal failure

PubMed Central

D’Apolito, Maria; Du, Xueliang; Zong, Haihong; Catucci, Alessandra; Maiuri, Luigi; Trivisano, Tiziana; Pettoello-Mantovani, Massimo; Campanozzi, Angelo; Raia, Valeria; Pessin, Jeffrey E.; Brownlee, Michael; Giardino, Ida

2009-01-01

Although supraphysiological concentrations of urea are known to increase oxidative stress in cultured cells, it is generally thought that the elevated levels of urea in chronic renal failure patients have negligible toxicity. We previously demonstrated that ROS increase intracellular protein modification by O-linked β-N-acetylglucosamine (O-GlcNAc), and others showed that increased modification of insulin signaling molecules by O-GlcNAc reduces insulin signal transduction. Because both oxidative stress and insulin resistance have been observed in patients with end-stage renal disease, we sought to determine the role of urea in these phenotypes. Treatment of 3T3-L1 adipocytes with urea at disease-relevant concentrations induced ROS production, caused insulin resistance, increased expression of adipokines retinol binding protein 4 (RBP4) and resistin, and increased O-GlcNAc–modified insulin signaling molecules. Investigation of a mouse model of surgically induced renal failure (uremic mice) revealed increased ROS production, modification of insulin signaling molecules by O-GlcNAc, and increased expression of RBP4 and resistin in visceral adipose tissue. Uremic mice also displayed insulin resistance and glucose intolerance, and treatment with an antioxidant SOD/catalase mimetic normalized these defects. The SOD/catalase mimetic treatment also prevented the development of insulin resistance in normal mice after urea infusion. These data suggest that therapeutic targeting of urea-induced ROS may help reduce the high morbidity and mortality caused by end-stage renal disease. PMID:19955654

Antihepatotoxic effect of golden berry (Physalis peruviana Linn.) in carbon tetrachloride (CCl4) intoxicated rats.

PubMed

Taj, Darakhshan; Khan, Hira; Sultana, Viqar; Ara, Jehan; Ehteshamul-Haque, Syed

2014-05-01

Liver is the main site in the body for intense metabolism and excretion. A number of chemicals and drugs which are used routinely cause liver damage. The present study investigates the antihepatotoxic effect of Physalis peruviana whole ripe fruit, water and ethanol extracts of fruit in normal as well as in carbon tetrachloride (CCl(4)) intoxicated rats. The CCl(4) treated rats showed marked elevation in liver enzymes: alanine transaminse, aspratate transaminase, alkaline phosphatase, lactate dehydrogenase and other biochemical parameters: bilirubin, creatinine and urea, thus indicating liver injury. Whereas animal treated/fed with various preparations of Physalis peruviana showed significant lowering effect (p<0.05) in the elevated levels of serum markers like ALAT, ASAT, ALP, LDH, creatinine, urea and bilirubin indicating the protection against hepatic cell damage. The water extract of Physalis peruviana showed highest activity in both rat models while ripe fruit and ethanol extract showed moderate activity compared to standard drug.

Sialic acid-to-urea ratio as a measure of airway surface hydration

PubMed Central

Hill, David B.; Button, Brian; Shi, Shuai; Jania, Corey; Duncan, Elizabeth A.; Doerschuk, Claire M.; Chen, Gang; Ranganathan, Sarath; Stick, Stephen M.; Boucher, Richard C.

2017-01-01

Although airway mucus dehydration is key to pathophysiology of cystic fibrosis (CF) and other airways diseases, measuring mucus hydration is challenging. We explored a robust method to estimate mucus hydration using sialic acid as a marker for mucin content. Terminal sialic acid residues from mucins were cleaved by acid hydrolysis from airway samples, and concentrations of sialic acid, urea, and other biomarkers were analyzed by mass spectrometry. In mucins purified from human airway epithelial (HAE), sialic acid concentrations after acid hydrolysis correlated with mucin concentrations (r2 = 0.92). Sialic acid-to-urea ratios measured from filters applied to the apical surface of cultured HAE correlated to percent solids and were elevated in samples from CF HAEs relative to controls (2.2 ± 1.1 vs. 0.93 ± 1.8, P < 0.01). Sialic acid-to-urea ratios were elevated in bronchoalveolar lavage fluid (BALF) from β-epithelial sodium channel (ENaC) transgenic mice, known to have reduced mucus hydration, and mice sensitized to house dust mite allergen. In a translational application, elevated sialic acid-to-urea ratios were measured in BALF from young children with CF who had airway infection relative to those who did not (5.5 ± 3.7 vs. 1.9 ± 1.4, P < 0.02) and could be assessed simultaneously with established biomarkers of inflammation. The sialic acid-to-urea ratio performed similarly to percent solids, the gold standard measure of mucus hydration. The method proved robust and has potential to serve as flexible techniques to assess mucin hydration, particularly in samples like BALF in which established methods such as percent solids cannot be utilized. PMID:28062483

Is elevated creatinine a reliable marker for methanol toxicity in nitromethane-containing model fuel ingestions in children?

PubMed

Padmanabhan, Pradeep; Spiller, Henry A; Ross, Mitchell P; Bosse, George M

2011-01-01

In the absence of a rapid serum methanol level estimation, it is difficult to assess the risk from unintentional childhood ingestion of model fuels containing methanol and nitromethane (MFNM). Previous reports have documented false elevations of serum creatinine from the nitromethane in these fuels, suggesting its utility as a readily available marker of significant methanol ingestion. We performed a 2-year retrospective chart review of cases of ingestion of MFNM in children, with both a methanol level and measured creatinine level. Seven children, ages 19 months to 3 years, ingested MFNM. All seven children were seen in a hospital and had measured methanol and creatinine levels. All blood samples for methanol and creatinine were drawn within 3 hours of ingestion with methanol estimation delayed up to 24 hours. Creatinine ranged from 0.39 (0.034 mmol/l) to 10.7 mg/dl (0.95 mmol/l). All methanol levels were <10 mg/dl (0.31 mmol/l) or reported as negative. Fomepizole was initiated empirically in two patients due to delay in obtaining methanol analysis results. Transient elevations of creatinine occurred in five of the seven children. Blood urea nitrogen was within normal limits, and there was no history of renal impairment in these children, suggesting the elevated creatinine was mostly related to nitromethane ingestion. No child had a significantly elevated methanol level. Elevated creatinine level, as measured by Jaffe colorimetric method, is not a reliable marker for elevated methanol levels after unintentional ingestion of MFNM.

Urea cycle disorders: a case report of a successful treatment with liver transplant and a literature review.

PubMed

Foschi, Francesco Giuseppe; Morelli, Maria Cristina; Savini, Sara; Dall'Aglio, Anna Chiara; Lanzi, Arianna; Cescon, Matteo; Ercolani, Giorgio; Cucchetti, Alessandro; Pinna, Antonio Daniele; Stefanini, Giuseppe Francesco

2015-04-07

The urea cycle is the final pathway for nitrogen metabolism. Urea cycle disorders (UCDs) include a variety of genetic defects, which lead to inefficient urea synthesis. Elevated blood ammonium level is usually dominant in the clinical pattern and the primary manifestations affect the central nervous system. Herein, we report the case of a 17-year-old girl who was diagnosed with UCD at the age of 3. Despite a controlled diet, she was hospitalized several times for acute attacks with recurrent life risk. She came to our attention for a hyperammonemic episode. We proposed an orthotopic liver transplant (OLT) as a treatment; the patient and her family were in complete agreement. On February 28, 2007, she successfully received a transplant. Following the surgery, she has remained well, and she is currently leading a normal life. Usually for UCDs diet plays the primary therapeutic role, while OLT is often considered as a last resort. Our case report and the recent literature data on the quality of life and prognosis of traditionally treated patients vs OLT patients, support OLT as a primary intervention to prevent life-threatening acute episodes and chronic mental impairment.

3-Methylglutaconic aciduria, a frequent but underrecognized finding in carbamoyl phosphate synthetase I deficiency.

PubMed

Rokicki, Dariusz; Pajdowska, Magdalena; Trubicka, Joanna; Thong, Meow-Keong; Ciara, Elżbieta; Piekutowska-Abramczuk, Dorota; Pronicki, Maciej; Sikora, Roman; Haidar, Rijad; Ołtarzewski, Mariusz; Jabłońska, Ewa; Muthukumarasamy, Premala; Sthaneswar, Pavai; Gan, Chin-Seng; Krajewska-Walasek, Małgorzata; Carrozzo, Rosalba; Verrigni, Daniela; Semeraro, Michela; Rizzo, Cristiano; Taurisano, Roberta; Alhaddad, Bader; Kovacs-Nagy, Reka; Haack, Tobias B; Dionisi-Vici, Carlo; Pronicka, Ewa; Wortmann, Saskia B

2017-08-01

The urea cycle disorder carbamoyl phosphate synthetase I deficiency is an important differential diagnosis in the encephalopathic neonate. This intoxication type inborn error of metabolism often leads to neonatal death or severe and irreversible damage of the central nervous system, even despite appropriate treatment. Timely diagnosis is crucial, but can be difficult on routine metabolite level. Here, we report ten neonates from eight families (finally) diagnosed with CPS1 deficiency at three tertiary metabolic centres. In seven of them the laboratory findings were dominated by significantly elevated urinary 3-methylglutaconic acid levels which complicated the diagnostic process. Our findings are both important for the differential diagnosis of patients with urea cycle disorders and also broaden the differential diagnosis of hyperammonemia associated with 3-methylglutaconic aciduria, which was earlier only reported in TMEM70 and SERAC1 defect. Copyright © 2017 Elsevier B.V. All rights reserved.

Decoupling of ammonium regulation and ntcA transcription in the diazotrophic marine cyanobacterium Trichodesmium sp. IMS101

PubMed Central

Post, Anton F; Rihtman, Branko; Wang, Qingfeng

2012-01-01

Nitrogen (N) physiology in the marine cyanobacterium Trichodesmium IMS101 was studied along with transcript accumulation of the N-regulatory gene ntcA and of two of its target genes: napA (nitrate assimilation) and nifH (N2 fixation). N2 fixation was impaired in the presence of nitrite, nitrate and urea. Strain IMS101 was capable of growth on these combined N sources at <2 μ but growth rates declined at elevated concentrations. Assimilation of nitrate and urea was impaired in the presence of ammonium. Whereas ecologically relevant N concentrations (2–20 μ) suppressed growth and assimilation, much higher concentrations were required to affect transcript levels. Transcripts of nifH accumulated under nitrogen-fixing conditions; these transcript levels were maintained in the presence of nitrate (100 μ) and ammonium (20 μ). However, nifH transcript levels were below detection at ammonium concentrations >20 μ. napA mRNA was found at low levels in both N2-fixing and ammonium-utilizing filaments, and it accumulated in filaments grown with nitrate. The positive effect of nitrate on napA transcription was abolished by ammonium additions of >200 μ. This effect was restored upon addition of the glutamine synthetase inhibitor -methionin--sulfoximine. Surprisingly, ntcA transcript levels remained high in the presence of ammonium, even at elevated concentrations. These findings indicate that ammonium repression is decoupled from transcriptional activation of ntcA in Trichodesmium IMS101. PMID:21938021

Decoupling of ammonium regulation and ntcA transcription in the diazotrophic marine cyanobacterium Trichodesmium sp. IMS101.

PubMed

Post, Anton F; Rihtman, Branko; Wang, Qingfeng

2012-03-01

Nitrogen (N) physiology in the marine cyanobacterium Trichodesmium IMS101 was studied along with transcript accumulation of the N-regulatory gene ntcA and of two of its target genes: napA (nitrate assimilation) and nifH (N(2) fixation). N(2) fixation was impaired in the presence of nitrite, nitrate and urea. Strain IMS101 was capable of growth on these combined N sources at <2 μM but growth rates declined at elevated concentrations. Assimilation of nitrate and urea was impaired in the presence of ammonium. Whereas ecologically relevant N concentrations (2-20 μM) suppressed growth and assimilation, much higher concentrations were required to affect transcript levels. Transcripts of nifH accumulated under nitrogen-fixing conditions; these transcript levels were maintained in the presence of nitrate (100 μM) and ammonium (20 μM). However, nifH transcript levels were below detection at ammonium concentrations >20 μM. napA mRNA was found at low levels in both N(2)-fixing and ammonium-utilizing filaments, and it accumulated in filaments grown with nitrate. The positive effect of nitrate on napA transcription was abolished by ammonium additions of >200 μM. This effect was restored upon addition of the glutamine synthetase inhibitor L-methionin-DL-sulfoximine. Surprisingly, ntcA transcript levels remained high in the presence of ammonium, even at elevated concentrations. These findings indicate that ammonium repression is decoupled from transcriptional activation of ntcA in Trichodesmium IMS101.

Role of urea in the postprandial urine concentration cycle of the insectivorous bat Antrozous pallidus.

PubMed

Bassett, John E

2004-02-01

Insectivorous bats, which feed once daily, produce maximally concentrated urine only after feeding. The role of urea as an osmolyte in this process was investigated in pallid bats (Antrozous pallidus) in the laboratory. Following a 24-h fast, plasma and urine were sampled before and 2 h after feeding in postprandial (PP) animals and before and 2 h after similar treatment without feeding in nonfed (NF) animals. Food consumption by PP animals and handling of NF animals had no effect on blood water content as measured by hematocrit and plasma oncotic pressure. Food consumption increased both plasma osmolality (P(osm)) and plasma urea (P(urea)) by as much as 15%. Food consumption also increased urine osmolality (U(osm)) and urine urea (U(urea)) by 50-100%. Feeding increased U(osm) regardless of changes in P(osm), and elevation of U(osm) resulted primarily from increased U(urea). In NF bats, P(osm) and P(urea) were unchanged, while U(osm) and U(urea) increased by as much as 25%. Again, increased U(osm) resulted primarily from increased U(urea). The PP urine concentration cycle of pallid bats resulted from increased urea excretion in response to apparent rapid urea synthesis. Bats rapidly metabolized protein and excreted urea following feeding when body water was most plentiful.

The effect of dietary protein restriction on the secretory dynamics of 1 alpha-hydroxycorticosterone and urea in the dogfish, Scyliorhinus canicula: a possible role for 1 alpha-hydroxycorticosterone in sodium retention.

PubMed

Armour, K J; O'Toole, L B; Hazon, N

1993-08-01

The putative osmoregulatory role of the unique elasmobranch corticosteroid, 1 alpha-hydroxycorticosterone (1 alpha-OH-B), was investigated using dietary protein restriction as a means of limiting urea biosynthetic ability. Groups of dogfish (Scyliorhinus canicula) were adapted to either a high or a low protein diet (HPD and LPD respectively) and the secretory dynamics of urea and 1 alpha-OH-B were determined following acclimation to normal (100%), 130% and 50% sea water. In normal sea water, LPD fish showed significantly decreased blood production of urea compared with fish fed a HPD (P < 0.05), and the plasma urea concentration required to maintain iso-osmolality was achieved only by a substantial decrease in urea clearance from the plasma. Unlike HPD fish, LPD fish in 130% sea water had no apparent ability to increase plasma urea concentration. An alternative strategy adopted by these animals was the retention of high plasma concentrations of Na+ and Cl-, which increased plasma osmolality and tended to decrease osmotic water loss. Concomitant with the increased ion concentrations, plasma 1 alpha-OH-B concentration was also greatly elevated in LPD fish indicating that the steroid may be acting to minimize Na+ (and Cl-) excretion at osmoregulatory sites such as the rectal gland, kidney and gills. This and a previous study have also demonstrated that 1 alpha-OH-B concentration is elevated in 50% sea water. Decreases in plasma Na+ concentration are tolerated down to 75% sea water, whereafter Na+ is preferentially retained and further decreases in osmolality are achieved by reductions in plasma urea concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Altered Expression of Urea Cycle Enzymes in Amyloid-β Protein Precursor Overexpressing PC12 Cells and in Sporadic Alzheimer's Disease Brain.

PubMed

Jęśko, Henryk; Lukiw, Walter J; Wilkaniec, Anna; Cieślik, Magdalena; Gąssowska-Dobrowolska, Magdalena; Murawska, Emilia; Hilgier, Wojciech; Adamczyk, Agata

2018-01-01

Urea cycle enzymes may play important yet poorly characterized roles in Alzheimer's disease (AD). Our previous results showed that amyloid-β (Aβ) affects urea cycle enzymes in rat pheochromocytoma (PC12) cells. The aim of the present study was to investigate the changes in arginases, other urea cycle enzymes, and nitric oxide synthases (NOSs) in PC12 cells transfected with AβPP bearing the double 'Swedish' mutation (APPsw, K670M/N671L) and in postmortem sporadic AD brain hippocampus; the mutation intensifies Aβ production and strongly associates with AD neuropathology. mRNA expression was analyzed using real-time PCR in cell cultures and DNA microarrays in hippocampal CA1 area of human AD brains. Arginase activity was measured spectrophotometrically, and arginine, ornithine, and citrulline levels by high-performance liquid chromatography. Our data demonstrated that the expression and activity of arginases (Arg1 and Arg2), as well as the expression of argininosuccinate synthase (Ass) were significantly reduced in APPsw cells compared to control. However, argininosuccinate lyase (Asl) was upregulated in APPsw cells. Real-time PCR analysis revealed significant elevation of neuronal nitric oxide synthase (Nnos) mRNA in APPsw cells, without changes in the endothelial Enos, whereas inducible Inos was undetectable. The changes were found to follow closely those observed in the human hippocampal CA1 region of sporadic AD brains. The changes in enzyme expression were accompanied in APPsw cells by significantly elevated citrulline, ornithine, and arginine. Our findings demonstrate that AβPP/Aβ alters arginine metabolism and induces a shift of cellular homeostasis that may support the oxidative/nitrosative stress observed in AD.

Skin application of urea-containing cream affected cutaneous arterial sympathetic nerve activity, blood flow, and water evaporation.

PubMed

Horii, Yuko; Tanida, Mamoru; Shen, Jiao; Fujisaki, Yosiyuki; Fuyuki, Risa; Hashimoto, Kazuko; Niijima, Akira; Nakashima, Toshihiro; Nagai, Katsuya

2011-02-01

We observed that olfactory stimulation with scent of grapefruit oil elevated the activities of sympathetic nerves, and increased the plasma glycerol concentration and blood pressure. In contrast, olfactory stimulation with scent of lavender oil had opposite effects in rats. These suggest that changes in autonomic activities cause physiological functions via histaminergic H1 and H3 receptor. Moreover, it has been reported that somatic sensory stimulation affected autonomic neurotransmission. To examine effects of skin application of urea-containing cream on cutaneous arterial sympathetic nerve activity (CASNA), blood flow, and transepidermal water loss (TEWL). The activity of CASNA was determined by electrophysiological method, and cutaneous blood flow was determined using laser flowmeter in urethane-anesthetized rats, TEWL was measured using VapoMeter in the back skin of HWY hairless rats. CASNA was markedly and significantly inhibited by skin application of 10% urea-containing cream, whereas cutaneous blood flow was significantly elevated via histaminergic H3-receptor. In conscious hairless rats, TEWL was significantly decreased 24 h after application of 10% urea-containing cream to the back skin. These findings suggest that skin application of 10% urea-containing cream increases the cutaneous blood flow and water retaining ability, and that histaminergic H3-receptors may mediate these effects. © 2010 John Wiley & Sons A/S.

Utilization of urea and expression profiles of related genes in the dinoflagellate Prorocentrum donghaiense

PubMed Central

Jing, Xiaoli; Lin, Senjie; Zhang, Huan; Koerting, Claudia; Yu, Zhigang

2017-01-01

Urea has been shown to contribute more than half of total nitrogen (N) required by phytoplankton in some estuaries and coastal waters and to provide a substantial portion of the N demand for many harmful algal blooms (HABs) of dinoflagellates. In this study, we investigated the physiological and transcriptional responses in Prorocentrum donghaiense to changes in nitrate and urea availability. We found that this species could efficiently utilize urea as sole N source and achieve comparable growth rate and photosynthesis capability as it did under nitrate. These physiological parameters were markedly lower in cultures grown under nitrate- or urea-limited conditions. P. donghaiense N content was similarly low under nitrate- or urea-limited culture condition, but was markedly higher under urea-replete condition than under nitrate-replete condition. Carbon (C) content was consistently elevated under N-limited condition. Consequently, the C:N ratio was as high as 21:1 under nitrate- or urea-limitation, but 7:1 under urea-replete condition and 9:1 to 10:1 under nitrate-replete condition. Using quantitative reverse transcription PCR, we investigated the expression pattern for four genes involved in N transport and assimilation. The results indicated that genes encoding nitrate transport, urea hydrolysis, and nickel transporter gene were sensitive to changes in general N nutrient availability whereas the urea transporter gene responded much more strongly to changes in urea concentration. Taken together, our study shows the high bioavailability of urea, its impact on C:N stoichiometry, and the sensitivity of urea transporter gene expression to urea availability. PMID:29117255

Utilization of urea and expression profiles of related genes in the dinoflagellate Prorocentrum donghaiense.

PubMed

Jing, Xiaoli; Lin, Senjie; Zhang, Huan; Koerting, Claudia; Yu, Zhigang

2017-01-01

Urea has been shown to contribute more than half of total nitrogen (N) required by phytoplankton in some estuaries and coastal waters and to provide a substantial portion of the N demand for many harmful algal blooms (HABs) of dinoflagellates. In this study, we investigated the physiological and transcriptional responses in Prorocentrum donghaiense to changes in nitrate and urea availability. We found that this species could efficiently utilize urea as sole N source and achieve comparable growth rate and photosynthesis capability as it did under nitrate. These physiological parameters were markedly lower in cultures grown under nitrate- or urea-limited conditions. P. donghaiense N content was similarly low under nitrate- or urea-limited culture condition, but was markedly higher under urea-replete condition than under nitrate-replete condition. Carbon (C) content was consistently elevated under N-limited condition. Consequently, the C:N ratio was as high as 21:1 under nitrate- or urea-limitation, but 7:1 under urea-replete condition and 9:1 to 10:1 under nitrate-replete condition. Using quantitative reverse transcription PCR, we investigated the expression pattern for four genes involved in N transport and assimilation. The results indicated that genes encoding nitrate transport, urea hydrolysis, and nickel transporter gene were sensitive to changes in general N nutrient availability whereas the urea transporter gene responded much more strongly to changes in urea concentration. Taken together, our study shows the high bioavailability of urea, its impact on C:N stoichiometry, and the sensitivity of urea transporter gene expression to urea availability.

Toxicologic Characterization of a Novel Explosive, Triaminoguanidinium-1-methyl-5-nitriminotetrazolate (TAG-MNT), in Female Rats and in vitro Assays

DTIC Science & Technology

2011-03-01

inflammation, hepatocyte degeneration, centrilobular hepatocyte hyper- trophy, increased mitoses, megakaryocytic hepatocytes, and bile duct ...of 2 g/L. However, TAG-MNT was cytotoxic to bacteria and a human liver cell line at 250 mg/L and greater. Unlike RDX, TAG-MNT did not have an...food intake, weight loss, increased kidney weight, leucopenia, and elevated blood urea nitrogen and creatinine levels. Leucopenia, increased liver mass

A longitudinal study of urea cycle disorders.

PubMed

Batshaw, Mark L; Tuchman, Mendel; Summar, Marshall; Seminara, Jennifer

2014-01-01

The Urea Cycle Disorders Consortium (UCDC) is a member of the NIH funded Rare Diseases Clinical Research Network and is performing a longitudinal study of 8 urea cycle disorders (UCDs) with initial enrollment beginning in 2006. The consortium consists of 14 sites in the U.S., Canada and Europe. This report summarizes data mining studies of 614 patients with UCDs enrolled in the UCDC's longitudinal study protocol. The most common disorder is ornithine transcarbamylase deficiency, accounting for more than half of the participants. We calculated the overall prevalence of urea cycle disorders to be 1/35,000, with 2/3rds presenting initial symptoms after the newborn period. We found the mortality rate to be 24% in neonatal onset cases and 11% in late onset cases. The most common precipitant of clinical hyperammonemic episodes in the post-neonatal period was intercurrent infections. Elevations in both blood ammonia and glutamine appeared to be biomarkers for neurocognitive outcome. In terms of chronic treatment, low protein diet appeared to result in normal weight but decreased linear growth while N-scavenger therapy with phenylbutyrate resulted in low levels of branched chain amino acids. Finally, we found an unexpectedly high risk for hepatic dysfunction in patients with ornithine transcarbamylase deficiency. This natural history study illustrates how a collaborative study of a rare genetic disorder can result in an improved understanding of morbidity and disease outcome. Copyright © 2014 Elsevier Inc. All rights reserved.

Analyses of plasma for metabolic and hormonal changes in rats flown aboard Cosmos 2044

NASA Technical Reports Server (NTRS)

Merrill, Alfred H., Jr.; Wang, Elaine; Mullins, Richard E.; Grindeland, Richard E.; Popova, Irina A.

1992-01-01

Plasmas samples from rats flown aboard Cosmos 2044 were analyzed for the levels of key metabolites, electrolytes, enzymes, and hormones. The major differences between the flight group and the synchronous control were elevations in glucose, cholesterol, phosphate, creatinine, blood urea nitrogen, lactate dehydrogenase, and aspartate aminotransferase and decreased levels of thyroxine. Most of these differences were not mimicked by tail suspension of ground-based rats; however, both flight and suspended rats exhibited inhibited testosterone secretion. Corticosterone, immunoreactive growth hormone, and prolactin showed inconsistent differences from the various control groups, suggesting that the levels of these hormones were not due to actual or simulated microgravity.

Urea transporters and sweat response to uremia.

PubMed

Keller, Raymond W; Bailey, James L; Wang, Yanhua; Klein, Janet D; Sands, Jeff M

2016-06-01

In humans, urea is excreted in sweat, largely through the eccrine sweat gland. The urea concentration in human sweat is elevated when compared to blood urea nitrogen. The sweat urea nitrogen (UN) of patients with end-stage kidney disease (ESRD) is increased when compared with healthy humans. The ability to produce sweat is maintained in the overwhelming majority of ESRD patients. A comprehensive literature review found no reports of sweat UN neither in healthy rodents nor in rodent models of chronic kidney disease (CKD). Therefore, this study measured sweat UN concentrations in healthy and uremic rats. Uninephrectomy followed by renal artery ligation was used to remove 5/6 of renal function. Rats were then fed a high-protein diet to induce uremia. Pilocarpine was used to induce sweating. Sweat droplets were collected under oil. Sweat UN was measured with a urease assay. Serum UN was measured using a fluorescent ortho-pthalaldehyde reaction. Immunohistochemistry (IHC) was accomplished with a horseradish peroxidase and diaminobenzidine technique. Sweat UN in uremic rats was elevated greater than two times compared to healthy pair-fed controls (220 ± 17 and 91 ± 15 mmol/L, respectively). Post hoc analysis showed a significant difference between male and female uremic sweat UN (279 ± 38 and 177 ± 11 mmol/L, respectively.) IHC shows, for the first time, the presence of the urea transporters UT-B and UT-A2 in both healthy and uremic rat cutaneous structures. Future studies will use this model to elucidate how rat sweat UN and other solute excretion is altered by commonly prescribed diuretics. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

EFFECTS OF BACTERIAL ENDOTOXINS ON METABOLISM

PubMed Central

Berry, L. Joe; Smythe, Dorothy S.

1961-01-01

In vitro secretion of glycocorticoids by adrenal glands pooled from several control mice was compared with that of glands removed from animals following injections of either ACTH or endotoxin. Both substances prevent glycocorticoid synthesis stimulated in vitro with ACTH. Cholesterol content of adrenal glands under these conditions was nearly depleted, indicating maximal response to ACTH or endotoxin prior to their removal for the in vitro tests. In an effort to account physiologically for the manner in which endotoxin suppresses or prevents the rise in urinary nitrogen excreted in response to ACTH, blood non-protein nitrogen levels (NPN) were determined. The following experimental conditions resulted in increased urinary nitrogen excretion but did not alter blood NPN: cortisone given alone or at the same time as endotoxin; ACTH alone; dichloroisoproterenol (DCI) given concurrently with endotoxin; and lactalbumin digest injected intraperitoneally. Increases (2- to 3-fold) in blood NPN were observed when endotoxin was given alone, concurrently with ACTH, or 3 hours prior to cortisone, DCI, or lactalbumin digest. Urinary nitrogen excretion showed no change under these conditions. The elevation in blood NPN in endotoxin-poisoned mice was found to be due almost entirely to urea nitrogen and not to amino acid nitrogen or to other nitrogenous wastes. Blood clearance of mulin, phenol red excretion, and urea elimination were each determined in control and in endotoxin-poisoned mice. The latter mice showed impaired renal function. Treatment with diuretics (diuril and aminophylline) failed to alter oliguria or elevated blood NPN. Hydergine treatment was also without effect. Total carcass NPN and urinary nitrogen excretion data were combined to give a picture of total protein catabolized by mice under different experimental conditions. Cortisone injected at the same time as endotoxin or 3 hours later resulted in the same increase in total NPN. However, in the former case all the extra nitrogen appeared in the urine while in the latter it remained in the carcass. ACTH given alone or concurrently with endotoxin produced large increases in total NPN but less in poisoned mice. This suggests that endotoxin suppresses adrenal response to ACTH. Urea injected into normal mice was recovered quantitatively in urine while in endotoxin-poisoned mice it was partitioned between carcass and urine. Elevation of carcass NPN by means of urea injections failed to alter the lethality of an LD70 dose of endotoxin. PMID:19867206

Effect of mesenchymal stem cells on anti-Thy1,1 induced kidney injury in albino rats

PubMed Central

Sakr, Saber; Rashed, Laila; Zarouk, Waheba; El-Shamy, Rania

2013-01-01

Objective To evaluate the effect of mesenchymal stem cells (MSCs) in rats with anti-Thy1,1 nephritis. Methods Female albino rats were divided into three groups, control group, anti-Thy1,1 group and treatment with i.v. MSCs group. MSCs were derived from bone marrow of male albino rats, Y-chromosome gene was detected by polymerase chain reaction in the kidney. Serum urea and creatinine were estimated for all groups. Kidney of all studied groups was examined histologically and histochemically (total carbohydrates and total proteins). DNA fragmentation and expression of α-SMA were detected. Results Kidney of animals injected with anti-Thy1,1 showed inflammatory leucocytic infiltration, hypertrophied glomeruli, tubular necrosis and congestion in the renal blood vessels. The kidney tissue also showed reduction of carbohydrates and total proteins together with increase in apoptosis and in expression of α-SMA. Moreover, the levels of urea and creatinine were elevated. Treating animals with MSCs revealed that kidney tissue displayed an improvement in the histological and histochemical changes. Apoptosis and α-SMA expression were decreased, and the levels of urea and creatinine decreased. Conclusions The obtained results demonstrated the potential of MSCs to ameliorate the structure and function of the kidney in rats with anti-Thy1,1 nephritis possibly through the release of paracrine growth factor(s). PMID:23620833

Short communication: Urea hydrolysis in dairy cattle manure under different temperature, urea, and pH conditions.

PubMed

Moraes, L E; Burgos, S A; DePeters, E J; Zhang, R; Fadel, J G

2017-03-01

The objective of the study was to quantify the rate of urea hydrolysis in dairy cattle manure under different initial urea concentration, temperature, and pH conditions. In particular, by varying all 3 factors simultaneously, the interactions between them could also be determined. Fresh feces and artificial urine solutions were combined into a slurry to characterize the rate of urea hydrolysis under 2 temperatures (15°C and 35°C), 3 urea concentrations in urine solutions (500, 1,000, and 1,500 mg of urea-N/dL), and 3 pH levels (6, 7, and 8). Urea N concentration in slurry was analyzed at 0.0167, 1, 2, 4, 6, 8, 12, 16, 20, and 24 h after initial mixing. A nonlinear mixed effects model was used to determine the effects of urea concentration, pH, and temperature treatments on the exponential rate of urea hydrolysis and to predict the hydrolysis rate for each treatment combination. We detected a significant interaction between pH and initial urea level. Increasing urea concentration from 1,000 to 1,500 mg of urea-N/dL decreased the rate of urea hydrolysis across all pH levels. Across all pH and initial urea levels, the rate of urea hydrolysis increased with temperature, but the effect of pH was only observed for pH 6 versus pH 8 at the intermediate initial urea concentration. The fast rates of urea hydrolysis indicate that urea was almost completely hydrolyzed within a few hours of urine mixing with feces. The estimated urea hydrolysis rates from this study are likely maximum rates because of the thorough mixing before each sampling. Although considerable mixing of feces and urine occurs on the barn floor of commercial dairy operations from cattle walking through the manure, such mixing may be not as quick and thorough as in this study. Consequently, the urea hydrolysis rates from this study indicate the maximum loss of urea and should be accounted for in management aimed at mitigating ammonia emissions from dairy cattle manure under similar urea concentration, pH, and temperature conditions reported in this experiment. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Relationship among antineutrophil cytoplasmic antibody, blood urea nitrogen and complement in patients with eosinophilic granulomatosis polyangiitis (Churg-Strauss syndrome).

PubMed

Kawakami, Tamihiro; Kimura, Satoko; Takeuchi, Sora; Soma, Yoshinao

2013-07-01

Eosinophilic granulomatosis with polyangiitis (EGPA), also known as Churg-Strauss syndrome, is an antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis characterized by a history of asthma, hypereosinophilia. The prevalence of ANCA in EGPA is less common than in other ANCA-associated vasculitis. Increasing evidence of complement activation in the pathogenesis of ANCA-associated vasculitis has been provided by studies in animal models. We examined EGPA patients with cutaneous manifestations as an initial sign and investigated the correlations among clinical, serological and histopathological findings. We focused on differences among ANCA, blood urea nitrogen and complement levels such as complement 3 (C3), C4 and total complement hemolytic activity (CH50). We retrospectively investigated the records of 22 patients (11 male and 11 female) with EGPA admitted to our hospital from 1997-2012. Ten of the 22 patients (46%) were positive for serum myeloperoxidase (MPO)-ANCA. In contrast, all the patients were negative for serum proteinase 3 ANCA. There was a significantly positive correlation between serum CH50 and C4 levels in patients with EGPA. Serum blood urea nitrogen (BUN) levels differed significantly between MPO-ANCA-positive and -negative patients. Serum CH50 levels were higher in MPO-ANCA-positive patients compared to negative patients. Serum BUN levels were higher in elevated CH50 patients compared to normal and low CH50-negative patients. We propose that positive findings for MPO-ANCA with CH50 high activity may be a risk factor for developing renal insufficiency. Assuming there are correlations between the presence of ANCA and complements, earlier diagnosis based on initial efficacious treatment for EGPA. © 2013 Japanese Dermatological Association.

Metabolic Changes in Summer Active and Anuric Hibernating Free-Ranging Brown Bears (Ursus arctos)

PubMed Central

Stenvinkel, Peter; Fröbert, Ole; Anderstam, Björn; Palm, Fredrik; Eriksson, Monica; Bragfors-Helin, Ann-Christin; Qureshi, Abdul Rashid; Larsson, Tobias; Friebe, Andrea; Zedrosser, Andreas; Josefsson, Johan; Svensson, My; Sahdo, Berolla; Bankir, Lise; Johnson, Richard J.

2013-01-01

The brown bear (Ursus arctos) hibernates for 5 to 6 months each winter and during this time ingests no food or water and remains anuric and inactive. Despite these extreme conditions, bears do not develop azotemia and preserve their muscle and bone strength. To date most renal studies have been limited to small numbers of bears, often in captive environments. Sixteen free-ranging bears were darted and had blood drawn both during hibernation in winter and summer. Samples were collected for measurement of creatinine and urea, markers of inflammation, the calcium-phosphate axis, and nutritional parameters including amino acids. In winter the bear serum creatinine increased 2.5 fold despite a 2-fold decrease in urea, indicating a remarkable ability to recycle urea nitrogen during hibernation. During hibernation serum calcium remained constant despite a decrease in serum phosphate and a rise in FGF23 levels. Despite prolonged inactivity and reduced renal function, inflammation does not ensue and bears seem to have enhanced antioxidant defense mechanisms during hibernation. Nutrition parameters showed high fat stores, preserved amino acids and mild hyperglycemia during hibernation. While total, essential, non-essential and branched chain amino acids concentrations do not change during hibernation anorexia, changes in individual amino acids ornithine, citrulline and arginine indicate an active, although reduced urea cycle and nitrogen recycling to proteins. Serum uric acid and serum fructose levels were elevated in summer and changes between seasons were positively correlated. Further studies to understand how bears can prevent the development of uremia despite minimal renal function during hibernation could provide new therapeutic avenues for the treatment of human kidney disease. PMID:24039826

Metabolic changes in summer active and anuric hibernating free-ranging brown bears (Ursus arctos).

PubMed

Stenvinkel, Peter; Fröbert, Ole; Anderstam, Björn; Palm, Fredrik; Eriksson, Monica; Bragfors-Helin, Ann-Christin; Qureshi, Abdul Rashid; Larsson, Tobias; Friebe, Andrea; Zedrosser, Andreas; Josefsson, Johan; Svensson, My; Sahdo, Berolla; Bankir, Lise; Johnson, Richard J

2013-01-01

The brown bear (Ursus arctos) hibernates for 5 to 6 months each winter and during this time ingests no food or water and remains anuric and inactive. Despite these extreme conditions, bears do not develop azotemia and preserve their muscle and bone strength. To date most renal studies have been limited to small numbers of bears, often in captive environments. Sixteen free-ranging bears were darted and had blood drawn both during hibernation in winter and summer. Samples were collected for measurement of creatinine and urea, markers of inflammation, the calcium-phosphate axis, and nutritional parameters including amino acids. In winter the bear serum creatinine increased 2.5 fold despite a 2-fold decrease in urea, indicating a remarkable ability to recycle urea nitrogen during hibernation. During hibernation serum calcium remained constant despite a decrease in serum phosphate and a rise in FGF23 levels. Despite prolonged inactivity and reduced renal function, inflammation does not ensue and bears seem to have enhanced antioxidant defense mechanisms during hibernation. Nutrition parameters showed high fat stores, preserved amino acids and mild hyperglycemia during hibernation. While total, essential, non-essential and branched chain amino acids concentrations do not change during hibernation anorexia, changes in individual amino acids ornithine, citrulline and arginine indicate an active, although reduced urea cycle and nitrogen recycling to proteins. Serum uric acid and serum fructose levels were elevated in summer and changes between seasons were positively correlated. Further studies to understand how bears can prevent the development of uremia despite minimal renal function during hibernation could provide new therapeutic avenues for the treatment of human kidney disease.

Characteristic Metabolism of Free Amino Acids in Cetacean Plasma: Cluster Analysis and Comparison with Mice

PubMed Central

Miyaji, Kazuki; Nagao, Kenji; Bannai, Makoto; Asakawa, Hiroshi; Kohyama, Kaoru; Ohtsu, Dai; Terasawa, Fumio; Ito, Shu; Iwao, Hajime; Ohtani, Nobuyo; Ohta, Mitsuaki

2010-01-01

From an evolutionary perspective, the ancestors of cetaceans first lived in terrestrial environments prior to adapting to aquatic environments. Whereas anatomical and morphological adaptations to aquatic environments have been well studied, few studies have focused on physiological changes. We focused on plasma amino acid concentrations (aminograms) since they show distinct patterns under various physiological conditions. Plasma and urine aminograms were obtained from bottlenose dolphins, pacific white-sided dolphins, Risso's dolphins, false-killer whales and C57BL/6J and ICR mice. Hierarchical cluster analyses were employed to uncover a multitude of amino acid relationships among different species, which can help us understand the complex interrelations comprising metabolic adaptations. The cetacean aminograms formed a cluster that was markedly distinguishable from the mouse cluster, indicating that cetaceans and terrestrial mammals have quite different metabolic machinery for amino acids. Levels of carnosine and 3-methylhistidine, both of which are antioxidants, were substantially higher in cetaceans. Urea was markedly elevated in cetaceans, whereas the level of urea cycle-related amino acids was lower. Because diving mammals must cope with high rates of reactive oxygen species generation due to alterations in apnea/reoxygenation and ischemia-reperfusion processes, high concentrations of antioxidative amino acids are advantageous. Moreover, shifting the set point of urea cycle may be an adaption used for body water conservation in the hyperosmotic sea water environment, because urea functions as a major blood osmolyte. Furthermore, since dolphins are kept in many aquariums for observation, the evaluation of these aminograms may provide useful diagnostic indices for the assessment of cetacean health in artificial environments in the future. PMID:21072195

Feed-derived volatile basic nitrogen increases reactive oxygen species production of blood leukocytes in lactating dairy cows.

PubMed

Tsunoda, Ei; Gross, Josef J; Kawashima, Chiho; Bruckmaier, Rupert M; Kida, Katsuya; Miyamoto, Akio

2017-01-01

The present study investigated over 9 months the changes of fermentative quality of total mixed rations (TMR) containing grass silage (GS) as a major component, associated with changes in the volatile basic nitrogen (VBN) levels in an experimental dairy farm. Effects of VBN levels in TMR on metabolic parameters, reactive oxygen species (ROS) production by blood polymorphonuclear leukocytes (PMNs) and conception rates for dairy cows were analyzed. According to VBN levels in TMR during survey periods, three distinct phases were identified; phase A with low VBN; phase B with high VBN; and phase C with mid-VBN. Metabolic parameters in blood were all within normal range. However, during phases B and C, nitrogen metabolic indices such as blood urea nitrogen and milk urea nitrogen showed higher levels compared to those in phase A, and a simultaneous increase in ROS production by blood PMNs and the load on hepatic function in metabolic parameters was observed in the cows with a lower conception rate. This suggests that feeding TMR with elevated VBN levels due to poor fermented GS results in stimulation of ROS production by PMNs by ammonia, and negatively affects metabolism and reproductive performance in lactating dairy cow. © 2016 Japanese Society of Animal Science.

Gene Deletions Resulting in Increased Nitrogen Release by Azotobacter vinelandii: Application of a Novel Nitrogen Biosensor

PubMed Central

Eberhart, Lauren J.; Ohlert, Janet M.; Knutson, Carolann M.; Plunkett, Mary H.

2015-01-01

Azotobacter vinelandii is a widely studied model diazotrophic (nitrogen-fixing) bacterium and also an obligate aerobe, differentiating it from many other diazotrophs that require environments low in oxygen for the function of the nitrogenase. As a free-living bacterium, A. vinelandii has evolved enzymes and transporters to minimize the loss of fixed nitrogen to the surrounding environment. In this study, we pursued efforts to target specific enzymes and further developed screens to identify individual colonies of A. vinelandii producing elevated levels of extracellular nitrogen. Targeted deletions were done to convert urea into a terminal product by disrupting the urease genes that influence the ability of A. vinelandii to recycle the urea nitrogen within the cell. Construction of a nitrogen biosensor strain was done to rapidly screen several thousand colonies disrupted by transposon insertional mutagenesis to identify strains with increased extracellular nitrogen production. Several disruptions were identified in the ammonium transporter gene amtB that resulted in the production of sufficient levels of extracellular nitrogen to support the growth of the biosensor strain. Further studies substituting the biosensor strain with the green alga Chlorella sorokiniana confirmed that levels of nitrogen produced were sufficient to support the growth of this organism when the medium was supplemented with sufficient sucrose to support the growth of the A. vinelandii in coculture. The nature and quantities of nitrogen released by urease and amtB disruptions were further compared to strains reported in previous efforts that altered the nifLA regulatory system to produce elevated levels of ammonium. These results reveal alternative approaches that can be used in various combinations to yield new strains that might have further application in biofertilizer schemes. PMID:25888177

Spirulina platensis protects against gentamicin-induced nephrotoxicity in rats.

PubMed

Karadeniz, Ali; Yildirim, Abdulkadir; Simsek, Nejdet; Kalkan, Yildiray; Celebi, Fikret

2008-11-01

The present study aimed to investigate the protective effect of Spirulina platensis (SP) on gentamicin sulphate (GS)-induced changes in the levels of lipid peroxidation and endogenous antioxidants in the kidney of rats. Sprague-Dawley rats were treated in separate groups as follows for 7 consecutive days: control (C), gentamicin sulphate (100 mg/kg i.p.) (GS), Spirulina platensis (1000 mg/kg orally) (SP) and Spirulina platensis (1000 mg/kg orally) plus gentamicin sulphate (100 mg/kg i.p.) (SP + GS). The degree of protection was evaluated by determining the effects of Spirulina platensis on malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPX) and nitric oxide (NO), and plasma creatinine and urea levels were estimated in kidney homogenates to evaluate antioxidant activity, and the kidney was histologically examined as well. Spirulina platensis elicited significant nephroprotective activity by decreasing lipid peroxidation (MDA) and elevated the levels of GSH, SOD, GPX, NO, creatinine and urea. Furthermore, these biochemical observations were supplemented by histological examination of the rat kidneys. In conclusion, the present study indicates a very important role of reactive oxygen species (ROS) and the relation to renal dysfunction and point to the therapeutic potential of Spirulina platensis in gentamicin sulphate induced nephrotoxicity.

Ammonium Metabolism Enzymes Aid Helicobacter pylori Acid Resistance

PubMed Central

Miller, Erica F.

2014-01-01

The gastric pathogen Helicobacter pylori possesses a highly active urease to support acid tolerance. Urea hydrolysis occurs inside the cytoplasm, resulting in the production of NH3 that is immediately protonated to form NH4+. This ammonium must be metabolized or effluxed because its presence within the cell is counterproductive to the goal of raising pH while maintaining a viable proton motive force (PMF). Two compatible hypotheses for mitigating intracellular ammonium toxicity include (i) the exit of protonated ammonium outward via the UreI permease, which was shown to facilitate diffusion of both urea and ammonium, and/or (ii) the assimilation of this ammonium, which is supported by evidence that H. pylori assimilates urea nitrogen into its amino acid pools. We investigated the second hypothesis by constructing strains with altered expression of the ammonium-assimilating enzymes glutamine synthetase (GS) and glutamate dehydrogenase (GDH) and the ammonium-evolving periplasmic enzymes glutaminase (Ggt) and asparaginase (AsnB). H. pylori strains expressing elevated levels of either GS or GDH are more acid tolerant than the wild type, exhibit enhanced ammonium production, and are able to alkalize the medium faster than the wild type. Strains lacking the genes for either Ggt or AsnB are acid sensitive, have 8-fold-lower urea-dependent ammonium production, and are more acid sensitive than the parent. Additionally, we found that purified H. pylori GS produces glutamine in the presence of Mg2+ at a rate similar to that of unadenylated Escherichia coli GS. These data reveal that all four enzymes contribute to whole-cell acid resistance in H. pylori and are likely important for assimilation and/or efflux of urea-derived ammonium. PMID:24936052

Copper toxicity in the spiny dogfish (Squalus acanthias): urea loss contributes to the osmoregulatory disturbance.

PubMed

De Boeck, G; Hattink, J; Franklin, N M; Bucking, C P; Wood, S; Walsh, P J; Wood, C M

2007-08-30

Previous research showed that the spiny dogfish, Squalus acanthias, is much more sensitive to silver exposure than typical marine teleosts. The aim of the present study was to investigate if spiny dogfish were equally sensitive to copper exposure and whether the toxic mechanisms were the same. We exposed cannulated and non-cannulated spiny dogfish to measured concentrations of Cu (nominally 0, 500, 1000 and 1500 microg L(-1) Cu) for 72-96 h. All Cu exposures induced acidosis and lactate accumulation of either a temporary (500 microg L(-1)) or more persistent nature (1000 and 1500 microg L(-1)). At the two highest Cu concentrations, gill Na(+)/K(+)-ATPase activities were reduced by 45% (1000 microg L(-1)) and 62% (1500 microg L(-1)), and plasma Na(+) and Cl(-) concentrations increased by approximately 50 mM each. At the same time urea excretion doubled and plasma urea dropped by approximately 100 mM. Together with plasma urea, plasma TMAO levels dropped proportionally, indicating that the general impermeability of the gills was compromised. Overall plasma osmolarity did not change. Cu accumulation was limited with significant increases in plasma Cu and elevated gill and kidney Cu burdens at 1000 and 1500 microg L(-1). We conclude that Cu, like Ag, exerts toxic effect on Na(+)/K(+)-ATPase activities in the shark similar to those of teleosts, but there is an additional toxic action on elasmobranch urea retention capacities. With a 96 h LC(50) in the 800-1000 microg L(-1) range, overall sensitivity of spiny dogfish for Cu is, in contrast with its sensitivity to Ag, only slightly lower than in typical marine teleosts.

Can salivary creatinine and urea levels be used to diagnose chronic kidney disease in children as accurately as serum creatinine and urea levels? A case-control study.

PubMed

Renda, Rahime

2017-11-01

Children with chronic kidney disease (CKD) develop many metabolic changes in blood that often necessitate frequent biochemical analysis. Serum analysis is an invasive and painful procedure. It would be highly beneficial if a noninvasive alternative process to serum analysis in children were identified. Saliva can be collected noninvasively, repeatedly, and without the use of healthcare personnel. The aims of this study were to compare serum and salivary urea and creatinine levels in children with CKD and healthy controls, and to determine if salivary creatinine and urea levels can be used to diagnose CKD in children as accurately as serum creatinine and urea levels. This case-control study included 35 children with CKD and 28 healthy children as controls. Saliva and blood samples were collected for measurement of urea and creatinine levels. The urea and creatinine levels in serum and saliva in the CKD and control groups were compared using the independent samples Mann-Whitney U test. Correlations between the serum and salivary urea and creatinine levels were determined using Pearson's correlation coefficient. Receiver operating characteristic analysis was used to assess the diagnostic performance of salivary creatinine and cutoff values were identified. In the CKD group, the mean salivary creatinine level was 0.45 mg/dL and the mean salivary urea level was 0.11 mg/dL, versus 28.83 mg/dL and 21.78 mg/dL, respectively, in the control group. Stage 4 and 5 CKD patients had a mean salivary urea level of 31.35 mg/dL, as compared to 17.78 mg/dL in the control group. Serum urea and creatinine, and salivary creatinine were significantly higher in the CKD patients (regardless of disease stage) than in the controls (p < .05). The salivary urea level was significantly higher in the stage 4 and 5 CKD patients than in the controls (p < .05). There was a positive correlation between serum and salivary creatinine. The area under the curve for salivary creatinine was 0.805. The cutoff value for salivary creatinine was 0.125 mg/dL, with a sensitivity of 82.9% and specificity of 78.6%. Based on the positive correlation between the serum and saliva creatinine levels observed in the present study, we think saliva analysis could be used as a noninvasive alternative to blood analysis for diagnosing CKD in children.

SERUM AND PAROTID FLUIS UREA-LEVELS IN UNREALOADED HEALTHY YOUNG ADULTS

DTIC Science & Technology

Forty-four healthy young adult male subjects were given oral doses of urea, and parotid fluid and serum urea levels were studied for 1 to 3 hours. A...highly significant correlation between urea in serum and in parotid fluid (r equals 0.982) was found. The indication was that, with flow rate...carefully controlled, parotid fluid could be used interchangeably with serum in urea determination, regardless of the magnitude of the blood concentration. (Author)

The relationship between increased levels of Anti-dsDNA with clinical manifestation in patients with SLE in Haji Adam Malik General Hospital Medan

NASA Astrophysics Data System (ADS)

Marpaung, B.; Patrick, J.

2018-03-01

Systemic Lupus Erythematosus (SLE) is an autoimmune rheumatic disease characterized by widespread inflammation and affects any organism the body. Many autoimmune diseases result in autoantibody production, but Anti-dsDNA antibodies are highly specific to SLE. Previous study found that Anti-dsDNA antibodies are associated with severe clinical manifestations of lupus. The aim of this study was to examine the relationship between anti-dsDNA level with clinical features and laboratory findings in SLE patients. This cross-sectional study was conducted in Hospital Haji Adam Malik Medan in May-October 2016.We examine anti-dsDNA, clinical features and kidney laboratory profile in all patient. Data were statistically analyzed.81 SLE patients with median level of anti-dsDNA 294 (6.1-1317). There was no significant relationship between increased level of Anti-dsDNA with clinical manifestations (p>0.05). There were significant relationships between increased level of Anti-dsDNA with renal impairment (p=0.049), urea level (p=0.016), urine protein (p=0.042) and hematology disorder (p=0.005). Arthritis is the most frequent clinical manifestation (96.3%) followed by malar rash (77.8%). Elevated anti-dsDNA level was not related with clinical manifestations but there was significant relationship with hematology disorder, urea, creatinine, and proteinuria in SLE patents.

Renal Phenotype of UT-A Urea Transporter Knockout Mice

PubMed Central

Fenton, Robert A.; Flynn, Anneliese; Shodeinde, Adetola; Smith, Craig P.; Schnermann, Jurgen; Knepper, Mark A.

2006-01-01

The urea transporters UT-A1 and UT-A3 mediate rapid transepithelial urea transport across the inner medullary collecting duct (IMCD). In a previous study, using a new mouse model in which both UT-A1 and UT-A3 were genetically deleted from the IMCD (UT-A1/3−/− mice), we investigated the role of these transporters in the function of the renal inner medulla. Here we report a series of studies investigating more generally the renal phenotype of UT-A1/3−/− mice. Pathological screening revealed abnormalities in both the testis (increased size) and kidney (decreased size and vascular congestion) of UT-A1/3−/− mice. Total urinary nitrate and nitrite excretion rates in UT-A1/3−/− mice were more than double those in wildtype mice. Total renal blood flow was not different between UT-A1/3−/− and wildtype mice, but underwent a greater percentage decrease in response to NG-Nitro-L-arginine Methyl Ester Hydrochloride (L-NAME) infusion. Whole kidney glomerular filtration rate was not different in UT-A1/3−/− mice compared to controls and underwent a similar increase in response to a greater dietary protein intake. Fractional urea excretion was markedly elevated in UT-A1/3−/− mice on a 40% protein diet, reaching 102.4 ± 8.8% of the filtered load, suggesting that there may be active urea secretion along the renal tubule. Although there was a marked urinary concentrating defect in UT-A1/3−/− mice, there was no decrease in aquaporin-2 or -3 expression. Furthermore, although urea accumulation in the inner medulla was markedly attenuated, there was no decrease in NaCl concentration in tissue from outer medulla or 2 levels of the inner medulla. PMID:15829709

Peak hyperammonemia and atypical acute liver failure: The eruption of an urea cycle disorder during hyperemesis gravidarum.

PubMed

Weiss, Nicolas; Mochel, Fanny; Rudler, Marika; Demeret, Sophie; Lebray, Pascal; Conti, Filomena; Galanaud, Damien; Ottolenghi, Chris; Bonnefont, Jean-Paul; Dommergues, Marc; Bernuau, Jacques; Thabut, Dominique

2017-09-20

Inborn urea cycle disorders are under-recognised metabolic causes of hyperammonemia in adults. A 28-year-old primigravida, seven weeks pregnant, affected by hyperemesis gravidarum developed acute liver injury (ALI) and then acute liver failure (ALF) in less than 48 h. Because the patient developed atypical features, especially mildly elevated aminotransferases contrasting with very high blood ammonia levels (281 μmol/L), concomitant with normal serum creatinine, an inborn error of metabolism was suspected. We performed emergency metabolic analyses, stopped all protein intake and started with intravenous (i.v.) high caloric intake, nitrogen scavenger drugs and haemodialysis. The neurological and hepatic status of the patient quickly improved together with normalisation of her ammonemia levels. High plasma glutamine and urinary orotic acid, alongside low plasma arginine, citrulline and ornithine were suggestive of an ornithine transcarbamylase deficiency, later confirmed by molecular analyses. Foetal sex was female, as determined by foetal DNA analysis in maternal blood, and foetal development was unremarkable throughout the pregnancy. Delivery was induced at 39 weeks with a close monitoring of ammonemia levels and i.v. perfusion of carbohydrates and lipids during labour and immediately post-partum to avoid hypercatabolism. Delivery was uneventful and the patient delivered a healthy female baby. Urea cycle disorders should be contemplated in non-jaundiced patients with ALI or ALF, severe hyperammonemia and normal serum creatinine regardless of serum aminotransferase levels. The prompt recognition of this rare condition and the rapid initiation of adequate metabolic therapy are mandatory to prevent irreversible neurological sequelae and to avoid liver transplantation. Copyright © 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Utilization of dietary urea in rainbow trout.

PubMed

Kaushik, S J; Dabrowski, K R; Dabrowska, H; Olah, E; Luquet, P

1983-01-01

Experiments were conducted to examine the potential utilization of dietary urea by rainbow trout. A control diet and two diets supplemented with 1 and 3% of urea were fed to fish. Postprandial levels of urea and ammonia in blood plasma, and postprandial excretion of these metabolites were followed during 24 h. Apparent digestibility of urea in rainbow trout was very high (greater than 98%). Maximum values of urea levels in plasma were reached 6 h (32.3 +/- 10.2 micrograms/ml) after a meal in the control fish and respectively 6 h (83.4 +/- 18.4 micrograms/ml) and 8 h (250.3 +/- 96.1 micrograms/ml) after a meal in trout fed 1 and 3% urea diets. Peaks of urea excretion rates appeared 7-9 h after meal, coinciding with the highest circulating urea concentration. Total daily urea excretion amounted to 5.53, 10.43 and 33.80 mg urea N/100 mg N intake in trout fed the control, 1 and 3% urea diets, respectively. It is concluded that the dietary urea is readily absorbed in the digestive tract of trout but is totally excreted thus leading to no beneficial effect on nitrogen balance. This excretion of urea also takes place passively without any increase in energy demands.

Opposite effects on regulation of urea synthesis by early and late uraemia in rats.

PubMed

Nielsen, Susanne Schouw; Grøfte, Thorbjørn; Grønbaek, Henning; Tygstrup, Niels; Vilstrup, Hendrik

2007-04-01

Acute and chronic kidney failure lead to catabolism with loss of lean body mass. Up-regulation of hepatic urea synthesis may play a role for the loss of body nitrogen and for the level of uraemia. The aims were to investigate the effects of early and late experimental renal failure on the regulation of hepatic urea synthesis and the expression of urea cycle enzyme genes in the liver. We examined the in vivo capacity of urea nitrogen synthesis, mRNA levels of urea cycle enzyme genes, and N-balances 6 days and 21 days after 5/6th partial nephrectomy in rats, and compared these data with pair- and free-fed control animals. Compared with pair-fed animals, early uraemia halved the in vivo urea synthesis capacity and decreased urea gene expressions (P<0.05). In contrast, late uraemia up-regulated in vivo urea synthesis and expression of all urea genes (P<0.05), save that of the flux-generating enzyme carbamoyl phosphate synthetase. The N-balance in rats with early uraemia was markedly negative (P<0.05) and near zero in late uraemia. Early uraemia down-regulated urea synthesis, so hepatic ureagenesis was not in itself involved in the negative N-balance. In contrast, late uraemia up-regulated urea synthesis, which probably contributed towards the reduced N-balance of this condition. These time-dependent, opposite effects on the uraemia-induced regulation of urea synthesis in vivo were not related to food restriction and probably mostly reflected regulation on gene level.

The influence of feeding and fasting on plasma metabolites in the dogfish shark (Squalus acanthias).

PubMed

Wood, Chris M; Walsh, Patrick J; Kajimura, Makiko; McClelland, Grant B; Chew, Shit F

2010-04-01

Dogfish sharks are opportunistic predators, eating large meals at irregular intervals. Here we present a synthesis of data from several previous studies on responses in plasma metabolites after natural feeding and during prolonged fasting (up to 56days), together with new data on changes in plasma concentrations of amino acids and non-esterified fatty acids. Post-prandial and long-term fasting responses were compared to control sharks fasted for 7days, a typical inter-meal interval. A feeding frenzy was created in which dogfish were allowed to feed naturally on dead teleosts at two consumed ration levels, 2.6% and 5.5% of body weight. Most responses were more pronounced at the higher ration level. These included increases in urea and TMAO concentrations at 20h, followed by stability through to 56days of fasting. Ammonia levels were low and exhibited little short-term response to feeding, but declined to very low values during the extended fast. Glucose and beta-hydroxybutyrate both fell after feeding, the latter to a greater and more prolonged extent (up to 60h), whereas acetoacetate did not change. During prolonged fasting, glucose concentrations were well regulated, but beta-hydroxybutyrate increased to 2-3-fold control levels. Total plasma amino acid concentrations increased in a biphasic fashion, with peaks at 6-20h, and 48-60h after the meal, followed by homeostasis during the extended fast. Essential and non-essential amino acids generally followed this same pattern, though some exhibited different trends after feeding: taurine, beta-alanine, and glycine (decreases or stability), alanine and glutamine (modest prolonged increases), and threonine, serine, asparagine, and valine (much larger short-term increases). Plasma non-esterified fatty acid concentrations declined markedly through 48h after the 2.6% meal. These data are interpreted in light of companion studies showing elevations in aerobic metabolic rate, urea production, rectal gland function, metabolic base excretion, and activation of ornithine-urea cycle and aerobic enzymes after the meal, and muscle N-depletion but maintenance of osmolality and urea production during long-term fasting.

Association between the blood concentrations of ammonia and carnitine/amino acid of schizophrenic patients treated with valproic acid.

PubMed

Ando, Masazumi; Amayasu, Hideaki; Itai, Takahiro; Yoshida, Hisahiro

2017-01-01

Administration of valproic acid (VPA) is complicated with approximately 0.9% of patients developing hyperammonemia, but the pathogenesis of this adverse effect remains to be clarified. The aim of the present study was to search for mechanisms associated with VPA-induced hyperammonemia in the light of changes in serum amino acids concentrations associated with the urea cycle of schizophrenic patients. Blood samples (10 mL) were obtained from 37 schizophrenic patients receiving VPA for the prevention of violent behaviors in the morning after overnight fast. Blood concentrations of ammonia, VPA, free carnitine, acyl-carnitine, and 40 amino acids including glutamate and citrulline were measured for each patient. Univariate and multivariate regression analyses were performed to identify amino acids or concomitantly administered drugs that were associated with variability in the blood concentrations of ammonia. The blood ammonia level was positively correlated with the serum glutamate concentration ( r  = 0.44, p  < 0.01) but negatively correlated with glutamine ( r  = -0.41, p  = 0.01), citrulline ( r  = -0.42, p  = 0.01), and glycine concentrations ( r  = -0.54, p  < 0.01). It was also revealed that the concomitant administration of the mood stabilizers ( p  = 0.04) risperidone ( p  = 0.03) and blonanserin ( p  < 0.01) was positively associated with the elevation of the blood ammonia level. We hypothisized that VPA would elevate the blood ammonia level of schizophrenic patients. The observed changes in serum amino acids are compatible with urea cycle dysfunction, possibly due to reduced carbamoyl-phosphate synthase 1 (CPS1) activity. We conclude that VPA should be prudently prescribed to schizophrenic patients, particularly those receiving mood stabilizers or certain antipsychotics.

Greener on the Other Side: How Increased Urea Use may Promote Cyanobacterial Blooms

NASA Astrophysics Data System (ADS)

Erratt, K. J.; Creed, I. F.; Trick, C. G.

2017-12-01

The frequency of freshwater cyanobacterial blooms is on the rise in temperate regions around the world. The widespread use of chemical fertilizers linked to modern agricultural practices has enhanced the fertility of surface waters promoting the expansion of cyanobacteria dominated harmful algal blooms. While phosphorus (P) has been recognized as the principal agent regulating phytoplankton productivity in inland waters, elevated P is not the universal trigger for bloom initiation. P fertilizer applications across the globe have been outpaced by nitrogen (N) fertilizer use. Not only has the load of N entering surface waters increased, but its chemical composition has been altered. The use of inorganic-N fertilizers has been waned in favor of urea-based products, with urea now accounting for more than half of total N-fertilizer applications worldwide. This contemporary shift in fertilizer usage has coincided with the rise of cyanobacteria dominated harmful algal blooms in freshwaters. Here, we examined the relative success of urea as a N-source relative to inorganic N forms (NO3-, NH4+) for three common bloom-forming species of cyanobacteria: Microcystis aeruginosa, Dolichospermum flos-aque, and Synechococcus sp. We found that (1) urea was consistently drawdown more rapidly relative to inorganic N substrates, suggesting that cyanobacteria exhibit a preference for urea over inorganic N forms; (2) cyanobacteria consume urea in excess of cellular requirements; and (3) urea may offer cyanobacteria a competitive edge over eukaryotic algae by enhancing light absorption capabilities. As we push forward into the 21st century, our reliance on urea-based fertilizers is projected to escalate and it is critical that we understand the unintended consequences urea discharge could be having on receiving freshwaters.

Urea application promotes amino acid metabolism and membrane lipid peroxidation in Azolla.

PubMed

Chen, Jiana; Huang, Min; Cao, Fangbo; Pardha-Saradhi, P; Zou, Yingbin

2017-01-01

A pot experiment was conducted to evaluate the effect of urea on nitrogen metabolism and membrane lipid peroxidation in Azolla pinnata. Compared to controls, the application of urea to A. pinnata resulted in a 44% decrease in nitrogenase activity, no significant change in glutamine synthetase activity, 660% higher glutamic-pyruvic transaminase, 39% increase in free amino acid levels, 22% increase in malondialdehyde levels, 21% increase in Na+/K+- levels, 16% increase in Ca2+/Mg2+-ATPase levels, and 11% decrease in superoxide dismutase activity. In terms of H2O2 detoxifying enzymes, peroxidase activity did not change and catalase activity increased by 64% in urea-treated A. pinnata. These findings suggest that urea application promotes amino acid metabolism and membrane lipid peroxidation in A. pinnata.

Urea application promotes amino acid metabolism and membrane lipid peroxidation in Azolla

PubMed Central

Chen, Jiana; Cao, Fangbo; Pardha-Saradhi, P.; Zou, Yingbin

2017-01-01

A pot experiment was conducted to evaluate the effect of urea on nitrogen metabolism and membrane lipid peroxidation in Azolla pinnata. Compared to controls, the application of urea to A. pinnata resulted in a 44% decrease in nitrogenase activity, no significant change in glutamine synthetase activity, 660% higher glutamic-pyruvic transaminase, 39% increase in free amino acid levels, 22% increase in malondialdehyde levels, 21% increase in Na+/K+- levels, 16% increase in Ca2+/Mg2+-ATPase levels, and 11% decrease in superoxide dismutase activity. In terms of H2O2 detoxifying enzymes, peroxidase activity did not change and catalase activity increased by 64% in urea-treated A. pinnata. These findings suggest that urea application promotes amino acid metabolism and membrane lipid peroxidation in A. pinnata. PMID:28945775

Urea cycle disorders: a life-threatening yet treatable cause of metabolic encephalopathy in adults.

PubMed

Blair, Nicholas F; Cremer, Philip D; Tchan, Michel C

2015-02-01

Urea cycle disorders are inborn errors of metabolism that, in rare cases, can present for the first time in adulthood. We report a perplexing presentation in a woman 4 days postpartum of bizarre and out-of-character behaviour interspersed with periods of complete normality. Without any focal neurological signs or abnormality on initial investigations, the diagnosis became clear with the finding of a significantly elevated plasma ammonia level, just as she began to deteriorate rapidly. She improved following intravenous dextrose and lipid emulsion, together with sodium benzoate, arginine and a protein-restricted diet. She remains well 12 months later with no permanent sequelae. Whilst this is a rare presentation of an uncommon disease, it is a treatable disorder and its early diagnosis can prevent a fatal outcome. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Urea Cycle Defects: Early-Onset Disease Associated with A208T Mutation in OTC Gene-Expanding the Clinical Phenotype.

PubMed

Sánchez, Ana Isabel; Rincón, Alejandra; García, Mary; Suárez-Obando, Fernando

2017-01-01

Ornithine transcarbamylase deficiency (OMIM: 311250) is the most common disorder of urea cycle disorders, accounting for nearly 50% of all cases. We report a case of a two-month- old male patient, who attends our medical genetics consultation because of low citrulline levels and elevated glutamine to citrulline ratio detected by expanded newborn screening with tandem mass spectrometry. He is an asymptomatic male with a normal physical examination and appropriate neurodevelopmental milestones. The patient has a family history of one older brother who died at 18 months old from severe and sudden hyperammonemia and a maternal aunt who suddenly died at two years old. He had high plasma ammonium concentration and a confirmed OTC mutation (p.A208T). Usually, this mutation causes OTC deficiency of late onset in adult males. However, this report raises awareness about mutations previously described as a late-onset causing disease, which can cause severe hyperammonemia and high risk of dying at an early age.

Analysis of the stability of urea in dried blood spots collected and stored on filter paper.

PubMed

Quraishi, Rizwana; Lakshmy, Ramakrishnan; Mukhopadhyay, Ashok Kumar; Jailkhani, Bansi Lal

2013-05-01

The ability to use dry blood spots (DBSs) on filter paper for the analysis of urea levels could be an important diagnostic tool for areas that have limited access to laboratory facilities. We developed a method for the extraction and quantification of urea from DBSs that were stored on 3M Whatman filter paper and investigated the effect of long-term storage on the level of urea in DBSs. DBSs of 4.5 mm in diameter were used for our assay, and we determined the urea levels in blood using a commercially available enzymatic kit (UV GLDH-method; Randox laboratories Ltd., UK). The DBSs on filter discs were stored at 4℃ or at 37℃ for 120 days. The mean intra- and inter-assay coefficient of variance for our method of urea extraction from dried blood was 4.2% and 6.3%, respectively. We collected 75 fresh blood samples and compared the urea content of each fresh sample with the urea content of DBSs taken from corresponding fresh blood samples. Regression analysis reported a regression coefficient (r) value of 0.97 and a recovery of urea from dried spots was 102.2%. Urea concentrations in DBSs were stable for up to 120 and 90 days when stored at 4℃ and 37℃, respectively. Our results show that urea can be stored and quantitatively recovered from small volumes of blood that was collected on filter paper.

Urea.

PubMed

Wang, Hongkai; Ran, Jianhua; Jiang, Tao

2014-01-01

Urea is generated by the urea cycle enzymes, which are mainly in the liver but are also ubiquitously expressed at low levels in other tissues. The metabolic process is altered in several conditions such as by diets, hormones, and diseases. Urea is then eliminated through fluids, especially urine. Blood urea nitrogen (BUN) has been utilized to evaluate renal function for decades. New roles for urea in the urinary system, circulation system, respiratory system, digestive system, nervous system, etc., were reported lately, which suggests clinical significance of urea.

Moringa oleifera Supplemented Diets Prevented Nickel-Induced Nephrotoxicity in Wistar Rats

PubMed Central

Adeyemi, O. S.; Elebiyo, T. C.

2014-01-01

Background. The Moringa oleifera plant has been implicated for several therapeutic potentials. Objective. To evaluate whether addition of M. oleifera to diet has protective effect against nickel-induced nephrotoxicity in rats. Methodology. Male Wistar rats were assigned into six groups of five. The rats were given oral exposure to 20 mg/kg nickel sulphate (NiSO4) in normal saline and sustained on either normal diet or diets supplemented with Moringa oleifera at different concentrations for 21 days. 24 hours after cessation of treatments, all animals were sacrificed under slight anesthesia. The blood and kidney samples were collected for biochemical and histopathology analyses, respectively. Results. NiSO4 exposure reduced the kidney-to-body weight ratio in rats and caused significant elevation in the levels of plasma creatinine, urea, and potassium. Also, the plasma level of sodium was decreased by NiSO4 exposure. However, addition of M. oleifera to diets averted the nickel-induced alteration to the level of creatinine and urea. The histopathology revealed damaged renal tubules and glomerular walls caused by NiSO4 exposure. In contrast, the damages were ameliorated by the M. oleifera supplemented diets. Conclusion. The addition of M. oleifera to diet afforded significant protection against nickel-induced nephrotoxicity. PMID:25295181

Hypervitaminosis A causing hypercalcemia in cystic fibrosis. Case report and focused review.

PubMed

Safi, Khalid H; Filbrun, Amy G; Nasr, Samya Z

2014-10-01

Hypercalcemia is a rare complication of hypervitaminosis A. We report a pediatric patient with cystic fibrosis (CF) and pancreatic insufficiency who was found to have hypervitaminosis A causing hypercalcemia, complicated by nephrocalcinosis and renal impairment. The patient is a 4-year-old girl with pancreatic-insufficient CF, gastroesophageal reflux, oral aversion, and failure to thrive requiring gastrostomy tube placement. She was prescribed Source CF vitamins, but rarely received the full dose, due to emesis and intolerance. She had routine annual labs that revealed hypercalcemia with elevated blood urea nitrogen and creatinine, which were not present in her previous annual labs. Upon further questioning, her mother reported that she seemed more fatigued for a few weeks, had abdominal pain, and was urinating more frequently. Upon admission to the hospital, laboratory results revealed elevated HCO3, while serum levels of potassium, phosphorus, and albumin were within normal limits. Vitamin D (25-hydroxy) level was low, and vitamin A level was elevated. Extensive metabolic and hormonal workup for the etiology of the hypercalcemia revealed evidence of chronic renal insufficiency and elevated vitamin A levels. She had a renal ultrasound that revealed bilateral nephrocalciosis. Diagnosis of chronic hypervitaminosis A complicated by hypercalcemia was made and was managed by holding vitamin A supplements, aggressive diuresis, and prednisolone. This case emphasizes the importance of regular vitamin A monitoring in patients with CF. There is a wide variability for the lowest intake required to cause toxicity, and the lower limit to cause toxicity has not been determined.

The Effects of Acute Copper and Ammonia Challenges on Ammonia and Urea Excretion by the Blue Crab Callinectes sapidus.

PubMed

Zimmer, Alex M; Jorge, Marianna Basso; Wood, Chris M; Martins, Camila M G; Bianchini, Adalto

2017-04-01

Copper (Cu) is a persistent environmental contaminant that elicits several physiological disturbances in aquatic organisms, including a disruption in ammonia regulation. We hypothesized that exposure to Cu in a model crustacean (blue crab, Callinectes sapidus) acclimated to brackish water (2 ppt) would lead to hyperammonemia by stimulating an increase in ammonia production and/or by inhibiting ammonia excretion. We further hypothesized that urea production would represent an ammonia detoxification strategy in response to Cu. In a pilot experiment, exposure to 0, 100, and 200 µg/L Cu for 6 h caused significant concentration-dependent increases in ammonia excretion (J amm ). Based on these results, an acute 24-h 100 µg/L Cu exposure was conducted and this similarly caused an overall stimulation of J amm during the 24-h period, indicative of an increase in ammonia production. Terminal haemolymph total ammonia content (T amm ) was unchanged, suggesting that while ammonia production was increased, there was no inhibition of the excretion mechanism. In support of our second hypothesis, urea excretion (J urea ) increased in response to Cu exposure; haemolymph [urea] was unaffected. This suggested that urea production also was increased. To further test the hypothesis that J urea increased to prevent hyperammonemia during Cu exposure, crabs were exposed to high environmental ammonia (HEA; 2.5 mmol/L NH 4 HCO 3 ) for 12 h in a separate experiment. This led to a fourfold increase in haemolymph T amm , whereas J urea increased only transiently and haemolymph [urea] was unchanged, indicating that urea production likely does not contribute to the attenuation of hyperammonemia in blue crabs. Overall, Cu exposure in blue crabs led to increased ammonia and urea production, which were both eliminated by excretion. These results may have important implications in aquaculture systems where crabs may be exposed to elevated Cu and/or ammonia.

Elevated Cystatin C Levels Are Associated with Cognitive Impairment and Progression of Parkinson Disease.

PubMed

Hu, Wei-Dong; Chen, Jing; Mao, Cheng-Jie; Feng, Ping; Yang, Ya-Ping; Luo, Wei-Feng; Liu, Chun-Feng

2016-09-01

We investigated the relationship between serum cystatin C (CysC) levels and cognitive dysfunction and disease progression in patients with Parkinson disease. Previous studies have reported altered CysC levels in neurodegenerative disorders, but only a few studies have explored the role of CysC and its relationship to cognitive dysfunction in Parkinson disease. We measured serum levels of CysC, creatinine, urea, and uric acid in 142 patients with Parkinson disease and 146 healthy controls. We assessed disease progression using the Hoehn and Yahr scale, and cognitive function using the Montreal Cognitive Assessment (Beijing version). The patients with Parkinson disease had significantly higher CysC levels than the controls (P<0.001). CysC level correlated significantly with age (r=0.494, P<0.001), sex (r=0.150, P=0.011), and serum creatinine level (r=0.377, P<0.001), but not with levels of urea or uric acid (P>0.05). CysC level was a significant independent predictor of Parkinson disease (odds ratio=23.143, 95% confidence interval: 5.485-97.648, P<0.001) in multivariate logistic regression analysis. In the Parkinson disease group, a higher CysC level was associated with a more advanced Hoehn and Yahr stage (r=0.098, P<0.05) and a lower Montreal Cognitive Assessment score (r=-0.381, P=0.003). Serum CysC levels can predict disease severity and cognitive dysfunction in patients with Parkinson disease. The exact role of CysC remains to be determined.

Changes in milk urea around insemination are negatively associated with conception success in dairy cows.

PubMed

Albaaj, A; Foucras, G; Raboisson, D

2017-04-01

Dietary protein levels are a risk factor for poor reproductive performance. Conception is particularly impaired in cases of high blood or milk urea. The objective of this study was to investigate the association between conception and low milk urea or changes in milk urea around artificial insemination (AI). Data were obtained from the French Milk Control Program for a 4-yr period (2009-2012). Milk urea values between 250 and 450 mg/kg (4.3 and 7.7 mM) were considered intermediate (I), and values ≤150 mg/kg (2.6 mM) were considered low (L). Milk urea values before and after each AI were allocated into 4 classes representing the dynamics of milk urea (before-after; I-I, I-L, L-I, and L-L). Subclinical ketosis was defined using milk fat and protein contents before AI as proxies. A logistic regression with a Poisson correction and herd as a random variable was then performed on data from Holstein or all breeds of cows. The success of conception was decreased [relative risk (95% confidence interval) = 0.96 (0.94-0.99)] in low-urea cows compared with intermediate-urea cows after AI; no significant association was found for urea levels before AI. When combining data on urea before and after AI, I-L urea cows exhibited a 5 to 9% decrease in conception compared with I-I urea cows, and L-I urea cows showed no difference in conception success compared with I-I urea cows. A decreased conception success for L-L urea cows compared with I-I urea cows was observed for the analysis with cows of all breeds. This work revealed that a decrease in urea from intermediate (before AI) to low (after AI) is a risk factor for conception failure. Surveys of variation in milk urea in dairy cows close to breeding are highly recommended. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Hepatic urea biosynthesis in the euryhaline elasmobranch Carcharhinus leucas.

PubMed

Anderson, W Gary; Good, Jonathan P; Pillans, Richard D; Hazon, Neil; Franklin, Craig E

2005-10-01

Plasma urea levels and hepatic urea production in the euryhaline bull shark, Carcharhinus leucas, acclimated to freshwater and seawater environments were measured. It was found that plasma urea concentration increased with salinity and that this increase was, in part, the result of a significant increase in hepatic production of urea. This study provides direct evidence that hepatic production of urea plays an important role in the osmoregulatory strategy of C. leucas. (c) 2005 Wiley-Liss, Inc.

[Laboratory findings in patients with hemorrhagic fever with renal syndrome].

PubMed

Puljiz, Ivan; Kuzman, Ilija; Turcinov, Drago; Makek, Nikola; Markotić, Alemka

2005-01-01

To examine the frequency and distribution of hematologic and biochemical laboratory findings in 94 patients with hemorrhagic fever with renal syndrome (HFRS) in the epidemic year 2002. The following laboratory findings were retrospectively analyzed: erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), hemoglobin, hematocrit, leukocyte count and differential percentage (segmented neutrophils, band neutrophils, atypical lymphocytes), platelet count, coagulation tests, blood urea nitrogen (BUN), creatinine, urine, potassium, bilirubin (BIL), aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyltransferase (GT), alkaline phosphatase (ALP), and serum protein electrophoresis. The study included 94 HFRS patients treated at the Dr Fran Mihaljević University Hospital for Infectious Diseases in Zagreb during 2002. ESR increase, mostly mild to moderate, was found in 86.2% of study patients. Increased CRP was recorded in 98.9% of study patients, however, one-fourth had CRP higher than 100 mg/L. Leukocytosis was recorded in 38.3% (10.1 +/- 4.2 x 10(9)/L), thrombocytopenia in 89.4% patients (68.2 +/- 48.3 x 10(9)/L), and severe thrombocytopenia (x 10(9)/L) in six patients. Three patients had abnormal coagulation tests. Increased values of BUN and creatinine were recorded in more than a half of patients, while only four patients had mild hyperkalemia. Only three patinets required hemodialysis. Mildly to moderately increased values of aminotransferases (AST, ALT, GT) were observed in more than 2/3; hypoalbuminaemia in nearly 1/3, and elevated alpha-2 fraction in more than 2/3 of patients. The majority of patients had pathologic urine findings. First laboratory abnormalities were usually found between day 5 and 7 of the disease (increased CRP level, thrombocytopenia, leukocytosis, and elevation of hemoglobin and hematocrit). Biochemical abnormalities(elevation of cratinine and urea, increased levels of aminotransferases) usually occurred at the beginning of the second week, and ESR increase in the second week of disease. The majority of our patients had laboratory findings characteristic of HFRS. Thrombocytopenia and increased level of CRP were the most common laboratory findings during the first week of the disease. Renal and liver impairment occurred at the beginning of the second week of the disease.

Evaluation of carbon dioxide emission factor from urea during rice cropping season: A case study in Korean paddy soil

NASA Astrophysics Data System (ADS)

Kim, Gil Won; Jeong, Seung Tak; Kim, Gun Yeob; Kim, Pil Joo; Kim, Sang Yoon

2016-08-01

Fertilization with urea can lead to a loss of carbon dioxide (CO2) that was fixed during the industrial production process. The extent of atmospheric CO2 removal from urea manufacturing was estimated by the Industrial Processes and Product Use sector (IPPU sector). On its basis, the Intergovernmental Panel on Climate Change (IPCC) has proposed a value of 0.2 Mg C per Mg urea (available in 2006 revised IPCC guidelines for greenhouse gas inventories), which is the mass fractions of C in urea, as the CO2 emission coefficient from urea for the agricultural sector. Notably, due to the possibility of bicarbonate leaching to waters, all C in urea might not get released as CO2 to the atmosphere. Hence, in order to provide an accurate value of the CO2 emission coefficient from applied urea in the rice ecosystem, the CO2 emission factors were characterized under different levels of 13C-urea applied paddy field in the current study. The total CO2 fluxes and rice grain yields increased significantly with increasing urea application (110-130 kg N ha-1) and thereafter, decreased. However, with increasing 13C-urea application, a significant and proportional increase of the 13CO2sbnd C emissions from 13C-urea was also observed. From the relationships between urea application levels and 13CO2sbnd C fluxes from 13C-urea, the CO2sbnd C emission factor from urea was estimated to range between 0.0143 and 0.0156 Mg C per Mg urea. Thus, the CO2sbnd C emission factor of this study is less than that of the value proposed by IPCC. Therefore, for the first time, we propose to revise the current IPCC guideline value of CO2sbnd C emission factor from urea as 0.0143-0.0156 Mg C per Mg urea for Korean paddy soils.

Evaluation of anti-fatigue and immunomodulating effects of quercetin in strenuous exercise mice

NASA Astrophysics Data System (ADS)

Zhang, Wei-qiang

2017-04-01

The purpose of the present study was to investigate the anti-fatigue and immunomodulating effects of quercetin in strenuous exercise mice. Mice were given orally either corn oil or quercetin (20, 40 and 60 mg/kg body weight suspended in corn oil) by gavage once a day for 28 day. All mice were sacrificed after rotarod test and the major biochemical parameters were analyzed in serum and liver. The results indicated that quercetin possessed anti-fatigue effects by prolonging retention times, decreasing levels of blood lactate and serum urea nitrogen, and increasing levels of blood glucose, tissue glycogen and serum glucagon. Furthermore, quercetin could improve the immune function of fatigue mice by decreasing tumor necrosis factor-α levels, and elevated interleukin-10 levels. Quercetin possessed anti-fatigue effects may be related to its immunomodulating effects.

The dogfish shark (Squalus acanthias) increases both hepatic and extrahepatic ornithine urea cycle enzyme activities for nitrogen conservation after feeding.

PubMed

Kajimura, Makiko; Walsh, Patrick J; Mommsen, Thomas P; Wood, Chris M

2006-01-01

Urea not only is utilized as a major osmolyte in marine elasmobranchs but also constitutes their main nitrogenous waste. This study investigated the effect of feeding, and thus elevated nitrogen intake, on nitrogen metabolism in the Pacific spiny dogfish Squalus acanthias. We determined the activities of ornithine urea cycle (O-UC) and related enzymes in liver and nonhepatic tissues. Carbamoyl phosphate synthetase III (the rate-limiting enzyme of the O-UC) activity in muscle is high compared with liver, and the activities in both tissues increased after feeding. The contribution of muscle to urea synthesis in the dogfish body appears to be much larger than that of liver when body mass is considered. Furthermore, enhanced activities of the O-UC and related enzymes (glutamine synthetase, ornithine transcarbamoylase, arginase) were seen after feeding in both liver and muscle and were accompanied by delayed increases in plasma urea, trimethylamine oxide, total free amino acids, alanine, and chloride concentrations, as well as in total osmolality. The O-UC and related enzymes also occurred in the intestine but showed little change after feeding. Feeding did not change the rate of urea excretion, indicating strong N retention after feeding. Ammonia excretion, which constituted only a small percentage of total N excretion, was raised in fed fish, while plasma ammonia did not change, suggesting that excess ammonia in plasma is quickly ushered into synthesis of urea or protein. In conclusion, we suggest that N conservation is a high priority in this elasmobranch and that feeding promotes ureogenesis and growth. Furthermore, exogenous nitrogen from food is converted into urea not only by the liver but also by the muscle and to a small extent by the intestine.

Discovery of (R)-1-(7-chloro-2,2-bis(fluoromethyl)chroman-4-yl)-3-(3-methylisoquinolin-5-yl)urea (A-1165442): a temperature-neutral transient receptor potential vanilloid-1 (TRPV1) antagonist with analgesic efficacy.

PubMed

Voight, Eric A; Gomtsyan, Arthur R; Daanen, Jerome F; Perner, Richard J; Schmidt, Robert G; Bayburt, Erol K; DiDomenico, Stanley; McDonald, Heath A; Puttfarcken, Pamela S; Chen, Jun; Neelands, Torben R; Bianchi, Bruce R; Han, Ping; Reilly, Regina M; Franklin, Pamela H; Segreti, Jason A; Nelson, Richard A; Su, Zhi; King, Andrew J; Polakowski, James S; Baker, Scott J; Gauvin, Donna M; Lewis, LaGeisha R; Mikusa, Joseph P; Joshi, Shailen K; Faltynek, Connie R; Kym, Philip R; Kort, Michael E

2014-09-11

The synthesis and characterization of a series of selective, orally bioavailable 1-(chroman-4-yl)urea TRPV1 antagonists is described. Whereas first-generation antagonists that inhibit all modes of TRPV1 activation can elicit hyperthermia, the compounds disclosed herein do not elevate core body temperature in preclinical models and only partially block acid activation of TRPV1. Advancing the SAR of this series led to the eventual identification of (R)-1-(7-chloro-2,2-bis(fluoromethyl)chroman-4-yl)-3-(3-methylisoquinolin-5-yl)urea (A-1165442, 52), an analogue that possesses excellent pharmacological selectivity, has a favorable pharmacokinetic profile, and demonstrates good efficacy against osteoarthritis pain in rodents.

Effect of surfactants and temperature on the hyperfiltration performance of poly(ether/urea) membranes

NASA Technical Reports Server (NTRS)

Leban, M. I.; Wydeven, T. J.

1984-01-01

The individual and combined effects of pasteurization temperature (347 K) and surfactants (anionic, cationic, and neutral) on a poly(ether/urea) thin-film hyperfiltration membrane were studied. Performance of this positively charged membrane was measured in terms of sodium chloride rejection and water flux. The observed effect was mostly on water flux and minimal on salt rejection. Pasteurization temperature caused an irreversible flux decline (flux decline slope of 0.09). The gradual flux reduction caused by neutral and cationic surfactants was reversible, whereas the flux reduction caused by anionic surfactant was irreversible and of similar magnitude to flux reduction caused by pasteurization temperature. The effects of anionic surfactant and pasteurization temperature were additive. Because of flux decline at elevated temperatures the poly(ether/urea) membrane is not very attractive for long-term spaceflight use.

Genetic variation in the urea cycle: a model resource for investigating key candidate genes for common diseases.

PubMed

Mitchell, Sabrina; Ellingson, Clint; Coyne, Thomas; Hall, Lynn; Neill, Meaghan; Christian, Natalie; Higham, Catherine; Dobrowolski, Steven F; Tuchman, Mendel; Summar, Marshall

2009-01-01

The urea cycle is the primary means of nitrogen metabolism in humans and other ureotelic organisms. There are five key enzymes in the urea cycle: carbamoyl-phosphate synthetase 1 (CPS1), ornithine transcarbamylase (OTC), argininosuccinate synthetase (ASS1), argininosuccinate lyase (ASL), and arginase 1 (ARG1). Additionally, a sixth enzyme, N-acetylglutamate synthase (NAGS), is critical for urea cycle function, providing CPS1 with its necessary cofactor. Deficiencies in any of these enzymes result in elevated blood ammonia concentrations, which can have detrimental effects, including central nervous system dysfunction, brain damage, coma, and death. Functional variants, which confer susceptibility for disease or dysfunction, have been described for enzymes within the cycle; however, a comprehensive screen of all the urea cycle enzymes has not been performed. We examined the exons and intron/exon boundaries of the five key urea cycle enzymes, NAGS, and two solute carrier transporter genes (SLC25A13 and SLC25A15) for sequence alterations using single-stranded conformational polymorphism (SSCP) analysis and high-resolution melt profiling. SSCP was performed on a set of DNA from 47 unrelated North American individuals with a mixture of ethnic backgrounds. High-resolution melt profiling was performed on a nonoverlapping DNA set of either 47 or 100 unrelated individuals with a mixture of backgrounds. We identified 33 unarchived polymorphisms in this screen that potentially play a role in the variation observed in urea cycle function. Screening all the genes in the pathway provides a catalog of variants that can be used in investigating candidate diseases. Copyright 2008 Wiley-Liss, Inc.

Neuropsychiatric manifestations in late-onset urea cycle disorder patients.

PubMed

Serrano, Mercedes; Martins, Cecilia; Pérez-Dueñas, Belén; Gómez-López, Lilian; Murgui, Empar; Fons, Carmen; García-Cazorla, Angels; Artuch, Rafael; Jara, Fernando; Arranz, José A; Häberle, Johannes; Briones, Paz; Campistol, Jaume; Pineda, Mercedes; Vilaseca, Maria A

2010-03-01

Inherited urea cycle disorders represent one of the most common groups of inborn errors of metabolism. Late-onset urea cycle disorders caused by partial enzyme deficiencies may present with unexpected clinical phenotypes. We report 9 patients followed up in our hospital presenting late-onset urea cycle disorders who initially manifested neuropsychiatric/neurodevelopmental symptoms (the most prevalent neuropsychiatric/neurodevelopmental diagnoses were mental retardation, attention-deficit hyperactivity disorder [ADHD], language disorder, and delirium). Generally, these clinical pictures did not benefit from pharmacological treatment. Conversely, dietary treatment improved the symptoms. Regarding biochemical data, 2 patients showed normal ammonium but high glutamine levels. This study highlights the fact that neuropsychiatric/neurodevelopmental findings are common among the initial symptomatology of late-onset urea cycle disorders. The authors recommend that unexplained or nonresponsive neuropsychiatric/neurodevelopmental symptoms appearing during childhood or adolescence be followed by a study of ammonia and amino acid plasmatic levels to rule out a urea cycle disorder.

Effect of ammonia-generating diet on ovine serum and follicular fluid ammonia and urea levels, serum oestrogen and progesterone concentrations and granulosa cell functions.

PubMed

Nandi, S; Mondal, S; Pal, D T; Gupta, P S P

2016-04-01

This study was undertaken to elucidate the effect of ammonia-generating diet on serum and follicular fluid ammonia and urea levels, serum oestrogen and progesterone concentrations and granulosa cell growth and secretion parameters in ewes (Ovis aries). Ewes were fed with 14% CP diet (control) or ammonia-generating diet or ammonia-generating diet plus soluble sugar. The serum and follicular fluid ammonia and urea level, serum oestrogen and progesterone levels and granulosa cell (obtained from ovaries of slaughtered ewes) growth parameters and secretory activities were estimated. Ammonia-generating diet (high-protein diet) increased the serum ammonia and urea concentration. Supplementation of soluble sugar significantly reduced the ammonia concentration in serum with comparable levels as in control group; however, the urea level in the same group was higher than that observed in control group. Supplementation of soluble sugar significantly reduced the follicular fluid ammonia concentration; however, the level was significantly higher compared to control group. Supplementation of soluble sugar brought down the follicular fluid urea level comparable to that observed in control group. Oestrogen and progesterone levels remained unchanged in ewes fed with different types of diet. Oestrogen and progesterone secretion were significantly lowered from granulosa cells recovered from ewes fed with high ammonia-generating diet. Low metabolic activity and high incidence of apoptosis were observed in granulosa cells obtained from ovaries of ewes fed with ammonia-generating diet. Journal of Animal Physiology and Animal Nutrition © 2015 Blackwell Verlag GmbH.

Physiological adaptations to fasting in an actively wintering canid, the Arctic blue fox (Alopex lagopus).

PubMed

Mustonen, Anne-Mari; Pyykönen, Teija; Puukka, Matti; Asikainen, Juha; Hänninen, Sari; Mononen, Jaakko; Nieminen, Petteri

2006-01-01

This study investigated the physiological adaptations to fasting using the farmed blue fox (Alopex lagopus) as a model for the endangered wild arctic fox. Sixteen blue foxes were fed throughout the winter and 32 blue foxes were fasted for 22 d in Nov-Dec 2002. Half of the fasted blue foxes were food-deprived again for 22 d in Jan-Feb 2003. The farmed blue fox lost weight at a slower rate (0.97-1.02% body mass d(-1)) than observed previously in the arctic fox, possibly due to its higher initial body fat content. The animals experienced occasional fasting-induced hypoglycaemia, but their locomotor activity was not affected. The plasma triacylglycerol and glycerol concentrations were elevated during phase II of fasting indicating stimulated lipolysis, probably induced by the high growth hormone concentrations. The total cholesterol, HDL- and LDL-cholesterol, urea, uric acid and total protein levels and the urea:creatinine ratio decreased during fasting. Although the plasma levels of some essential amino acids increased, the blue foxes did not enter phase III of starvation characterized by stimulated proteolysis during either of the 22-d fasting procedures. Instead of excessive protein catabolism, it is liver dysfunction, indicated by the increased plasma bilirubin levels and alkaline phosphatase, alanine aminotransferase and aspartate aminotransferase activities, that may limit the duration of fasting in the species.

A current perspective on the compensatory effects of urea and methylamine on protein stability and function.

PubMed

Rahman, Safikur; Warepam, Marina; Singh, Laishram R; Dar, Tanveer Ali

2015-11-01

Urea is a strong denaturant and inhibits many enzymes but is accumulated intracellularly at very high concentrations (up to 3-4 M) in mammalian kidney and in many marine fishes. It is known that the harmful effects of urea on the macromolecular structure and function is offset by the accumulation of an osmolytic agent called methylamine. Intracellular concentration of urea to methylamines falls in the ratio of 2:1 to 3:2 (molar ratio). At this ratio, the thermodynamic effects of urea and methylamines on protein stability and function are believed to be algebraically additive. The mechanism of urea-methylamine counteraction has been widely investigated on various approaches including, thermodynamic, structural and functional aspects. Recent advances have also revealed atomic level insights of counteraction and various molecular dynamic simulation studies have yielded significant molecular level informations on the interaction between urea and methylamines with proteins. It is worthwhile that urea-methylamine system not only plays pivotal role for the survival and functioning of the renal medullary cells but also is a key osmoregulatory component of the marine elasmobranchs, holocephalans and coelacanths. Therefore, it is important to combine all discoveries and discuss the developments in context to physiology of the mammalian kidney and adaptation of the marine organisms. In this article we have for the first time reviewed all major developments on urea-counteraction systems to date. We have also discussed about other additional urea-counteraction systems discovered so far including urea-NaCl, urea-myoinsoitol and urea-molecular chaperone systems. Insights for the possible future research have also been highlighted. Copyright © 2015 Elsevier Ltd. All rights reserved.

Urea-N recycling in lactating dairy cows fed diets with 2 different levels of dietary crude protein and starch with or without monensin.

PubMed

Recktenwald, E B; Ross, D A; Fessenden, S W; Wall, C J; Van Amburgh, M E

2014-03-01

Rumensin (monensin; Elanco Animal Health, Greenfield, IN) has been shown to reduce ammonia production and microbial populations in vitro; thus, it would be assumed to reduce ruminal ammonia production and subsequent urea production and consequently affect urea recycling. The objective of this experiment was to determine the effects of 2 levels of dietary crude protein (CP) and 2 levels of starch, with and without Rumensin on urea-N recycling in lactating dairy cattle. Twelve lactating Holstein dairy cows (107 ± 21 d in milk, 647 kg ± 37 kg of body weight) were fed diets characterized as having high (16.7%) or low (15.3%) CP with or without Rumensin, while dietary starch levels (23 vs. 29%) were varied between 2 feeding periods with at least 7d of adaptation between measurements. Cows assigned to high or low protein and to Rumensin or no Rumensin remained on those treatments to avoid carryover effects. The diets consisted of approximately 40% corn silage, 20% alfalfa hay, and 40% concentrate mix specific to the treatment diets, with 0.5 kg of wheat straw added to the high starch diets to enhance effective fiber intake. The diets were formulated using Cornell Net Carbohydrate and Protein System (version 6.1), and the low-protein diets were formulated to be deficient for rumen ammonia to create conditions that should enhance the demand for urea recycling. The high-protein diets were formulated to be positive for both rumen ammonia and metabolizable protein. Rumen fluid, urine, feces, and milk samples were collected before and after a 72-h continuous jugular infusion of (15)N(15)N-urea. Total urine and feces were collected during the urea infusions for N balance measurements. Milk yield and dry matter intake were improved in cows fed the higher level of dietary CP and by Rumensin. Ruminal ammonia and milk and plasma urea nitrogen concentrations corresponded to dietary CP concentration. As has been shown in vitro, Rumensin reduced rumen ammonia concentration by approximately 23% but did not affect urea entry rate or gastrointestinal entry rate. Urea entry rate averaged approximately 57% of total N intake for cattle with and without Rumensin, and gastrointestinal rate was similar at 43 and 42% of N intake for cattle fed and not fed Rumensin, respectively. The cattle fed the high-protein diet had a 25% increase in urea entry rate and no effect of starch level was observed for any recycling parameters. Contrary to our hypothesis, Rumensin did not alter urea production and recycling. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Estimation of salivary sodium, potassium, calcium, phosphorus and urea in type II diabetic patients.

PubMed

Shirzaiy, Masoumeh; Heidari, Fatemeh; Dalirsani, Zohreh; Dehghan, Javid

2015-01-01

Diabetes mellitus is an endocrine disease due to insufficiency production of insulin that is associated with altered quantity and quality in salivary secretion. Alteration in saliva can reflect the changes in patients' blood. The collection of saliva is easy therefore; the assessment of saliva is suitable for screening tests of large population. The study aimed at evaluate some elements in diabetic patients' saliva. A total of 25 diabetic patients and age-sex matched control group enrolled into the study. Absorbance spectrophotometer technique was used for assessment of some salivary elements. The assessment of saliva showed that diabetics had unstimulated salivary flow rate of 0.18 ± 0.14 mL/min compared to 0.30 ± 0.12 mL/min for healthy individuals (P<0.01). Secretion of potassium and urea to saliva was significantly higher in diabetics compared to healthy group (P<0.05). In contrast calcium, sodium and phosphorus concentration was not significantly different in two groups. The level of salivary urea, potassium and phosphorus was significantly elevated in diabetic males compared to healthy males and the level of salivary calcium in diabetic females was significantly reduced compared to healthy females (P<0.05). There was not any significant difference in salivary sodium of healthy and diabetic persons according to gender (P>0.05). The finding showed that there were some alterations in salivary elements in diabetic patients even in well-controlled subjects compared to healthy group. Moreover, some salivary elements concentrations were various in diabetic and healthy subjects regarding to the sex. Assessment of salivary composition could be beneficial in oral health evaluation. Copyright © 2013 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Altered nitrogen balance and decreased urea excretion in male rats fed cafeteria diet are related to arginine availability.

PubMed

Sabater, David; Agnelli, Silvia; Arriarán, Sofía; Fernández-López, José-Antonio; Romero, María del Mar; Alemany, Marià; Remesar, Xavier

2014-01-01

Hyperlipidic diets limit glucose oxidation and favor amino acid preservation, hampering the elimination of excess dietary nitrogen and the catabolic utilization of amino acids. We analyzed whether reduced urea excretion was a consequence of higher NO x ; (nitrite, nitrate, and other derivatives) availability caused by increased nitric oxide production in metabolic syndrome. Rats fed a cafeteria diet for 30 days had a higher intake and accumulation of amino acid nitrogen and lower urea excretion. There were no differences in plasma nitrate or nitrite. NO(x) and creatinine excretion accounted for only a small part of total nitrogen excretion. Rats fed a cafeteria diet had higher plasma levels of glutamine, serine, threonine, glycine, and ornithine when compared with controls, whereas arginine was lower. Liver carbamoyl-phosphate synthetase I activity was higher in cafeteria diet-fed rats, but arginase I was lower. The high carbamoyl-phosphate synthetase activity and ornithine levels suggest activation of the urea cycle in cafeteria diet-fed rats, but low arginine levels point to a block in the urea cycle between ornithine and arginine, thereby preventing the elimination of excess nitrogen as urea. The ultimate consequence of this paradoxical block in the urea cycle seems to be the limitation of arginine production and/or availability.

The effects of crude protein concentration and slow release urea on nitrogen metabolism in Holstein steers.

PubMed

Holder, Vaughn B; El-Kadi, Samer W; Tricarico, Juan M; Vanzant, Eric S; McLeod, Kyle R; Harmon, David L

2013-04-01

This experiment was conducted to determine the effects of slow release urea (SRU) and its interaction with crude protein (CP) level in the diet on N metabolism in Holstein steers. Eight rumen-cannulated Holstein steers (body weight 265 ± 18 kg) were used in a replicated 4 × 4 Latin square design with a 2 × 2 factorial treatment structure. Treatment factors were the CP level in the diet, 10.9% versus 12.1% CP, and the non-protein nitrogen source used, urea versus SRU. Total collection of urine and faeces for 7 days allowed the estimation of N retention and diet digestibility. In addition, blood and rumen sampling allowed estimation of rumen fermentation and blood N profiles. Decreasing CP intake from 12.1% to 10.9% reduced urinary N output, but also reduced diet digestibility and N retention. When compared to urea, SRU did not alter N retention, but reduced ruminal ammonia and plasma urea concentrations. Although SRU did not improve N retention at either CP level, rumen ammonia and plasma urea concentrations were reduced, which may indicate that SRU may carry a lower risk for toxicity when compared to urea when fed at higher dietary concentrations.

Altered Nitrogen Balance and Decreased Urea Excretion in Male Rats Fed Cafeteria Diet Are Related to Arginine Availability

PubMed Central

Sabater, David; Arriarán, Sofía; Fernández-López, José-Antonio; Romero, María del Mar; Remesar, Xavier

2014-01-01

Hyperlipidic diets limit glucose oxidation and favor amino acid preservation, hampering the elimination of excess dietary nitrogen and the catabolic utilization of amino acids. We analyzed whether reduced urea excretion was a consequence of higher NOx; (nitrite, nitrate, and other derivatives) availability caused by increased nitric oxide production in metabolic syndrome. Rats fed a cafeteria diet for 30 days had a higher intake and accumulation of amino acid nitrogen and lower urea excretion. There were no differences in plasma nitrate or nitrite. NOx and creatinine excretion accounted for only a small part of total nitrogen excretion. Rats fed a cafeteria diet had higher plasma levels of glutamine, serine, threonine, glycine, and ornithine when compared with controls, whereas arginine was lower. Liver carbamoyl-phosphate synthetase I activity was higher in cafeteria diet-fed rats, but arginase I was lower. The high carbamoyl-phosphate synthetase activity and ornithine levels suggest activation of the urea cycle in cafeteria diet-fed rats, but low arginine levels point to a block in the urea cycle between ornithine and arginine, thereby preventing the elimination of excess nitrogen as urea. The ultimate consequence of this paradoxical block in the urea cycle seems to be the limitation of arginine production and/or availability. PMID:24707502

Increased plasma citrulline in mice marks diet-induced obesity and may predict the development of the metabolic syndrome.

PubMed

Sailer, Manuela; Dahlhoff, Christoph; Giesbertz, Pieter; Eidens, Mena K; de Wit, Nicole; Rubio-Aliaga, Isabel; Boekschoten, Mark V; Müller, Michael; Daniel, Hannelore

2013-01-01

In humans, plasma amino acid concentrations of branched-chain amino acids (BCAA) and aromatic amino acids (AAA) increase in states of obesity, insulin resistance and diabetes. We here assessed whether these putative biomarkers can also be identified in two different obesity and diabetic mouse models. C57BL/6 mice with diet-induced obesity (DIO) mimic the metabolic impairments of obesity in humans characterized by hyperglycemia, hyperinsulinemia and hepatic triglyceride accumulation. Mice treated with streptozotocin (STZ) to induce insulin deficiency were used as a type 1 diabetes model. Plasma amino acid profiling of two high fat (HF) feeding trials revealed that citrulline and ornithine concentrations are elevated in obese mice, while systemic arginine bioavailability (ratio of plasma arginine to ornithine + citrulline) is reduced. In skeletal muscle, HF feeding induced a reduction of arginine levels while citrulline levels were elevated. However, arginine or citrulline remained unchanged in their key metabolic organs, intestine and kidney. Moreover, the intestinal conversion of labeled arginine to ornithine and citrulline in vitro remained unaffected by HF feeding excluding the intestine as prime site of these alterations. In liver, citrulline is mainly derived from ornithine in the urea cycle and DIO mice displayed reduced hepatic ornithine levels. Since both amino acids share an antiport mechanism for mitochondrial import and export, elevated plasma citrulline may indicate impaired hepatic amino acid handling in DIO mice. In the insulin deficient mice, plasma citrulline and ornithine levels also increased and additionally these animals displayed elevated BCAA and AAA levels like insulin resistant and diabetic patients. Therefore, type 1 diabetic mice but not DIO mice show the "diabetic fingerprint" of plasma amino acid changes observed in humans. Additionally, citrulline may serve as an early indicator of the obesity-dependent metabolic impairments.

Infrared spectroscopic monitoring of urea addition to oriented strandboard resins

Treesearch

Chi-Leung So; Thomas L. Eberhardt; Ernest Hsu; Brian K. Via; Chung Y. Hse

2007-01-01

One of the variables in phenol formaldehyde adhesive resin formulation is the addition of urea, which allows the resin manufacturer to manipulate both product functionality and cost. Nitrogen content can be used as a measure of the level of urea addition because most of the nitrogen present is derived from urea added at the end of the preparation process. Nitrogen...

Mechanical Insight into Resistance of Betaine to Urea-Induced Protein Denaturation.

PubMed

Chen, Jiantao; Gong, Xiangjun; Zeng, Chaoxi; Wang, Yonghua; Zhang, Guangzhao

2016-12-08

It is known that urea can induce protein denaturation that can be inhibited by osmolytes. Yet, experimental explorations on this mechanism at the molecular level are still lacking. We have investigated the resistance of betaine to the urea-induced denaturation of lysozyme in aqueous solutions using low-field NMR. Our study demonstrates that urea molecules directly interact with lysozyme, leading to denaturation. However, betaine molecules interacting with urea more strongly than lysozyme can pull the bound urea molecules from lysozyme so that the protein is protected from denaturation. The number of urea molecules bound to a betaine molecule is given under different conditions. Proton NMR spectroscopy ( 1 H-NMR) and Fourier transform infrared spectroscopy reveal that the interaction between betaine and urea is through hydrogen bonding.

Exposure to acute severe hypoxia leads to increased urea loss and disruptions in acid-base and ionoregulatory balance in dogfish sharks (Squalus acanthias).

PubMed

Zimmer, Alex M; Wood, Chris M

2014-01-01

The effects of acute moderate (20% air O2 saturation; 6-h exposure) and severe (5% air O2 saturation; 4-h exposure) hypoxia on N-waste, acid-base, and ion balance in dogfish sharks (Squalus acanthias suckleyi) were evaluated. We predicted that the synthesis and/or retention of urea, which are active processes, would be inhibited by hypoxia. Exposure to moderate hypoxia had negligible effects on N-waste fluxes or systemic physiology, except for a modest rise in plasma lactate. Exposure to severe hypoxia led to a significant increase in urea excretion (Jurea), while plasma, liver, and muscle urea concentrations were unchanged, suggesting a loss of urea retention. Ammonia excretion (Jamm) was elevated during normoxic recovery. Moreover, severe hypoxia led to disruptions in acid-base balance, indicated by a large increase in plasma [lactate] and substantial decreases in arterial pHa and plasma [Formula: see text], as well as loss of ionic homeostasis, indicated by increases in plasma [Mg(2+)], [Ca(2+)], and [Na(+)]. We suggest that severe hypoxia in dogfish sharks leads to a reduction in active gill homeostatic processes, such as urea retention, acid-base regulation and ionoregulation, and/or an osmoregulatory compromise due to increased functional gill surface area. Overall, the results provide a comprehensive picture of the physiological responses to a severe degree of hypoxia in an ancient fish species.

Prolonged continuous intravenous infusion of the dipeptide L-alanine- L-glutamine significantly increases plasma glutamine and alanine without elevating brain glutamate in patients with severe traumatic brain injury

PubMed Central

2014-01-01

Introduction Low plasma glutamine levels are associated with worse clinical outcome. Intravenous glutamine infusion dose- dependently increases plasma glutamine levels, thereby correcting hypoglutaminemia. Glutamine may be transformed to glutamate which might limit its application at a higher dose in patients with severe traumatic brain injury (TBI). To date, the optimal glutamine dose required to normalize plasma glutamine levels without increasing plasma and cerebral glutamate has not yet been defined. Methods Changes in plasma and cerebral glutamine, alanine, and glutamate as well as indirect signs of metabolic impairment reflected by increased intracranial pressure (ICP), lactate, lactate-to-pyruvate ratio, electroencephalogram (EEG) activity were determined before, during, and after continuous intravenous infusion of 0.75 g L-alanine-L-glutamine which was given either for 24 hours (group 1, n = 6) or 5 days (group 2, n = 6) in addition to regular enteral nutrition. Lab values including nitrogen balance, urea and ammonia were determined daily. Results Continuous L-alanine-L-glutamine infusion significantly increased plasma and cerebral glutamine as well as alanine levels, being mostly sustained during the 5 day infusion phase (plasma glutamine: from 295 ± 62 to 500 ± 145 μmol/ l; brain glutamine: from 183 ± 188 to 549 ± 120 μmol/ l; plasma alanine: from 327 ± 91 to 622 ± 182 μmol/ l; brain alanine: from 48 ± 55 to 89 ± 129 μmol/ l; p < 0.05, ANOVA, post hoc Dunn’s test). Plasma glutamate remained unchanged and cerebral glutamate was decreased without any signs of cerebral impairment. Urea and ammonia were significantly increased within normal limits without signs of organ dysfunction (urea: from 2.7 ± 1.6 to 5.5 ± 1.5 mmol/ l; ammonia: from 12 ± 6.3 to 26 ± 8.3 μmol/ l; p < 0.05, ANOVA, post hoc Dunn’s test). Conclusions High dose L-alanine-L-glutamine infusion (0.75 g/ kg/ d up to 5 days) increased plasma and brain glutamine and alanine levels. This was not associated with elevated glutamate or signs of potential glutamate-mediated cerebral injury. The increased nitrogen load should be considered in patients with renal and hepatic dysfunction. Trial registration Clinicaltrials.gov NCT02130674. Registered 5 April 2014 PMID:24992948

Ornithine transcarbamylase and arginase I deficiency are responsible for diminished urea cycle function in the human hepatoblastoma cell line HepG2.

PubMed

Mavri-Damelin, Demetra; Eaton, Simon; Damelin, Leonard H; Rees, Myrddin; Hodgson, Humphrey J F; Selden, Clare

2007-01-01

A possible cell source for a bio-artificial liver is the human hepatblastoma-derived cell line HepG2 as it confers many hepatocyte functions, however, the urea cycle is not maintained resulting in the lack of ammonia detoxification via this cycle. We investigated urea cycle activity in HepG2 cells at both a molecular and biochemical level to determine the causes for the lack of urea cycle expression, and subsequently addressed reinstatement of the cycle by gene transfer. Metabolic labelling studies showed that urea production from 15N-ammonium chloride was not detectable in HepG2 conditioned medium, nor could 14C-labelled urea cycle intermediates be detected. Gene expression data from HepG2 cells revealed that although expression of three urea cycle genes Carbamoyl Phosphate Synthase I, Arginosuccinate Synthetase and Arginosuccinate Lyase was evident, Ornithine Transcarbamylase and Arginase I expression were completely absent. These results were confirmed by Western blot for arginase I, where no protein was detected. Radiolabelled enzyme assays showed that Ornithine Transcarbamylase functional activity was missing but that Carbamoyl Phosphate Synthase I, Arginosuccinate Synthetase and Arginosuccinate Lyase were functionally expressed at levels comparable to cultured primary human hepatocytes. To restore the urea cycle, HepG2 cells were transfected with full length Ornithine Transcarbamylase and Arginase I cDNA constructs under a CMV promoter. Co-transfected HepG2 cells displayed complete urea cycle activity, producing both labelled urea and urea cycle intermediates. This strategy could provide a cell source capable of urea synthesis, and hence ammonia detoxificatory function, which would be useful in a bio-artificial liver.

Salivary levels of phosphorus and urea as indices of their plasma levels in nephropathic patients.

PubMed

Bilancio, Giancarlo; Cavallo, Pierpaolo; Lombardi, Cinzia; Guarino, Ermanno; Cozza, Vincenzo; Giordano, Francesco; Palladino, Giuseppe; Cirillo, Massimo

2018-03-30

Phosphorus and urea are measurable in saliva. Measurements of saliva phosphorus (S-Pho) and saliva urea (S-Urea) could be useful because of low invasivity. Data are limited to saliva tests methodology and to correlations between plasma and saliva compositions. S-Pho and S-Urea were investigated focusing on blind duplicates, differences between collection sites, differences between collection times, freezing-thawing effects, and plasma-saliva correlations. Tests were performed using fresh saliva collected by synthetic swap early morning after overnight fast (standard). Methodology was investigated in fifteen healthy volunteers. Plasma-saliva correlations were investigated in thirty nephropathic outpatients. S-Pho and S-Urea in all measurements ranged above detection limits (0.3 mmol/L). In healthy volunteers, S-Pho and S-Urea were similar in duplicates (results for S-Pho and S-Urea: % difference between samples ≤ 4.85%; R between samples ≥ .976, P < .001), in samples from different mouth sites (≤4.24%; R ≥ .887, P < .001), and in samples of different days (≤5.61%; R ≥ .606, P < .01) but, compared to standard, were substantially lower in after-breakfast samples (-28.0% and -21.3%; R ≥ .786, P < .001) and slightly lower in frozen-thawed samples (-12.4% and -5.92%; R ≥ .742, P < .001). In nephropathic patients, S-Pho was higher than but correlated with plasma phosphorus (saliva/plasma ratio 4.80; R = .686, P < .001), whereas S-Urea and plasma urea were similar and correlated with each other (saliva/plasma ratio 0.96; R = .944, P < .001). Post-dialysis changes in S-Pho and S-Urea paralleled post-dialysis changes in plasma phosphorus and urea. S-Pho and S-Urea reflect plasma phosphorus and plasma urea. Early morning fasting fresh samples are advisable because collection time and freezing-thawing affect saliva tests. © 2018 Wiley Periodicals, Inc.

Persistent Low Level of Osterix Accelerates Interleukin-6 Production and Impairs Regeneration after Tissue Injury

PubMed Central

Baek, Wook-Young; Park, Seung-Yoon; Kim, Yeo Hyang; Lee, Min-A; Kwon, Tae-Hwan; Park, Kwon-Moo; de Crombrugghe, Benoit; Kim, Jung-Eun

2013-01-01

Osterix (Osx) is an essential transcription factor for osteoblast differentiation and bone formation. Osx knockout show a complete absence of bone formation, whereas Osx conditional knockout in osteoblasts produce an osteopenic phenotype after birth. Here, we questioned whether Osx has a potential role in regulating physiological homeostasis. In Osx heterozygotes expressing low levels of Osx in bones, the expression levels of pro-inflammatory cytokines were significantly elevated, indicating that reduced Osx expression may reflect an inflammatory-prone state. In particular, the expression of interleukin-6, a key mediator of chronic inflammation, was increased in Osx heterozygotes and decreased in Osx overexpressing osteoblasts, and transcriptionally down-regulated by Osx. Although no significant differences were revealed in renal morphology and function between Osx heterozygotes and wild-type under normoxic conditions, recovery of kidneys after ischemic damage was remarkably delayed in Osx heterozygotes, as indicated by elevated blood urea nitrogen and creatinine levels, and by morphological alterations consistent with acute tubular necrosis. Eventually, protracted low Osx expression level caused an inflammatory-prone state in the body, resulting in the enhanced susceptibility to renal injury and the delayed renal repair after ischemia/reperfusion. This study suggests that the maintenance of Osx expression in bone is important in terms of preventing the onset of an inflammatory-prone state. PMID:23922826

Milk urea testing as a tool to monitor reproductive performance in Ontario dairy herds.

PubMed

Godden, S M; Kelton, D F; Lissemore, K D; Walton, J S; Leslie, K E; Lumsden, J H

2001-06-01

Dairy herd improvement test-day data, including milk urea concentrations measured using infrared test method, were collected from 60 commercial Ontario Holstein dairy herds for a 13-mo period between December 1, 1995, and December 31, 1996. The objective of the study was to describe, at the cow and the group level, the relationship between DHI milk urea concentrations and reproductive performance in commercial dairy herds. When interpreted at the cow level, there was no association between milk urea and the risk for pregnancy from an insemination occurring within the 45-d period preceding test day. However, a negative curvilinear relationship existed between milk urea and the risk for pregnancy from a first, second, or third insemination event occurring within the 45-d period following test day, with the odds for pregnancy being highest when the milk urea on the test day preceding the insemination was either below 4.5 mmol/L or greater than 6.49 mmol/L, compared with a concentration between 4.5 and 6.49 mmol/L. When interpreted at the group level, there was no association between group mean milk urea for cows between 50 and 180 DIM, and the group conception rate for cows receiving a first, second, or third insemination event in the 45-d period either preceding or following test day. Thus, while DHI milk urea measurements may be useful as a management tool to improve the efficiency of production or reduce nitrogen excretion, through helping to optimize the efficiency of protein utilization, they may have limited utility as a monitoring or diagnostic tool for reproductive performance. The results of this study suggest that good fertility may be achieved across a broad range of milk urea concentrations.

Transgenic Restoration of Urea Transporter A1 Confers Maximal Urinary Concentration in the Absence of Urea Transporter A3.

PubMed

Klein, Janet D; Wang, Yanhua; Mistry, Abinash; LaRocque, Lauren M; Molina, Patrick A; Rogers, Richard T; Blount, Mitsi A; Sands, Jeff M

2016-05-01

Urea has a critical role in urinary concentration. Mice lacking the inner medullary collecting duct (IMCD) urea transporter A1 (UT-A1) and urea transporter A3 (UT-A3) have very low levels of urea permeability and are unable to concentrate urine. To investigate the role of UT-A1 in the concentration of urine, we transgenically expressed UT-A1 in knockout mice lacking UT-A1 and UT-A3 using a construct with a UT-A1 gene that cannot be spliced to produce UT-A3. This construct was inserted behind the original UT-A promoter to yield a mouse expressing only UT-A1 (UT-A1(+/+)/UT-A3(-/-)). Western blot analysis demonstrated UT-A1 in the inner medulla of UT-A1(+/+)/UT-A3(-/-) and wild-type mice, but not in UT-A1/UT-A3 knockout mice, and an absence of UT-A3 in UT-A1(+/+)/UT-A3(-/-) and UT-A1/UT-A3 knockout mice. Immunohistochemistry in UT-A1(+/+)/UT-A3(-/-) mice also showed negative UT-A3 staining in kidney and other tissues and positive UT-A1 staining only in the IMCD. Urea permeability in isolated perfused IMCDs showed basal permeability in the UT-A1(+/+)/UT-A3(-/-) mice was similar to levels in wild-type mice, but vasopressin stimulation of urea permeability in wild-type mice was significantly greater (100% increase) than in UT-A1(+/+)/UT-A3(-/-) mice (8% increase). Notably, basal urine osmolalities in both wild-type and UT-A1(+/+)/UT-A3(-/-) mice increased upon overnight water restriction. We conclude that transgenic expression of UT-A1 restores basal urea permeability to the level in wild-type mice but does not restore vasopressin-stimulated levels of urea permeability. This information suggests that transgenic expression of UT-A1 alone in mice lacking UT-A1 and UT-A3 is sufficient to restore urine-concentrating ability. Copyright © 2016 by the American Society of Nephrology.

Transgenic Restoration of Urea Transporter A1 Confers Maximal Urinary Concentration in the Absence of Urea Transporter A3

PubMed Central

Wang, Yanhua; Mistry, Abinash; LaRocque, Lauren M.; Molina, Patrick A.; Rogers, Richard T.; Blount, Mitsi A.; Sands, Jeff M.

2016-01-01

Urea has a critical role in urinary concentration. Mice lacking the inner medullary collecting duct (IMCD) urea transporter A1 (UT-A1) and urea transporter A3 (UT-A3) have very low levels of urea permeability and are unable to concentrate urine. To investigate the role of UT-A1 in the concentration of urine, we transgenically expressed UT-A1 in knockout mice lacking UT-A1 and UT-A3 using a construct with a UT-A1 gene that cannot be spliced to produce UT-A3. This construct was inserted behind the original UT-A promoter to yield a mouse expressing only UT-A1 (UT-A1+/+/UT-A3−/−). Western blot analysis demonstrated UT-A1 in the inner medulla of UT-A1+/+/UT-A3−/− and wild-type mice, but not in UT-A1/UT-A3 knockout mice, and an absence of UT-A3 in UT-A1+/+/UT-A3−/− and UT-A1/UT-A3 knockout mice. Immunohistochemistry in UT-A1+/+/UT-A3−/− mice also showed negative UT-A3 staining in kidney and other tissues and positive UT-A1 staining only in the IMCD. Urea permeability in isolated perfused IMCDs showed basal permeability in the UT-A1+/+/UT-A3−/− mice was similar to levels in wild-type mice, but vasopressin stimulation of urea permeability in wild-type mice was significantly greater (100% increase) than in UT-A1+/+/UT-A3−/− mice (8% increase). Notably, basal urine osmolalities in both wild-type and UT-A1+/+/UT-A3−/− mice increased upon overnight water restriction. We conclude that transgenic expression of UT-A1 restores basal urea permeability to the level in wild-type mice but does not restore vasopressin-stimulated levels of urea permeability. This information suggests that transgenic expression of UT-A1 alone in mice lacking UT-A1 and UT-A3 is sufficient to restore urine-concentrating ability. PMID:26407594

Does Amia Calva aestivate?

PubMed

McKenzie, D J; Randall, D J

1990-03-01

During gradual air exposure, Amia calva show no reduction in oxygen consumption, no increase in plasma urea levels or in urea excretion. Blood pH remains constant, and plasma total CO2, PCO 2, HCO3 (-). total ammonia and NH3 concentrations all rise significantly. Exposure to 923 μmol/l NH4Cl does not elicit an increase in urea production or airbreathing. Aquatic hypoxia without access to air does not cause a reduction in aerobic metabolism, and moderate levels result in death. These results suggest that Amia are incapable of aestivation, due to an inability to detoxify ammonia to urea and reduce metabolism, and die following three to five days of air exposure.

α-Ketoglutaramate: An overlooked metabolite of glutamine and a biomarker for hepatic encephalopathy and inborn errors of the urea cycle

PubMed Central

Cooper, Arthur J. L.; Kuhara, Tomiko

2013-01-01

Glutamine metabolism is generally regarded as proceeding via glutaminase-catalyzed hydrolysis to glutamate and ammonia, followed by conversion of glutamate to α-ketoglutarate catalyzed by glutamate dehydrogenase or by a glutamate-linked aminotransferase (transaminase). However, another pathway exists for the conversion of glutamine to α-ketoglutarate that is often overlooked, but is widely distributed in nature. This pathway, referred to as the glutaminase II pathway, consists of a glutamine transaminase coupled to ω-amidase. Transamination of glutamine results in formation of the corresponding α-keto acid, namely, α-ketoglutaramate (KGM). KGM is hydrolyzed by ω-amidase to α-ketoglutarate and ammonia. The net glutaminase II reaction is: L-Glutamine + α-keto acid + H2O → α-ketoglutarate + L-amino acid + ammonia. In this mini-review the biochemical importance of the glutaminase II pathway is summarized, with emphasis on the key component KGM. Forty years ago it was noted that the concentration of KGM is increased in the cerebrospinal fluid (CSF) of patients with hepatic encephalopathy (HE) and that the level of KGM in the CSF correlates well with the degree of encephalopathy. In more recent work, we have shown that KGM is markedly elevated in the urine of patients with inborn errors of the urea cycle. It is suggested that KGM may be a useful biomarker for many hyperammonemic diseases including hepatic encephalopathy, inborn errors of the urea cycle, citrin deficiency and lysinuric protein intolerance. PMID:24234505

Fatal coma in a young adult due to late-onset urea cycle deficiency presenting with a prolonged seizure: a case report.

PubMed

Alameri, Majid; Shakra, Mustafa; Alsaadi, Taoufik

2015-11-23

Unexplained hyperammonemic coma in adults can be a medical dilemma in the absence of triggering factors and known comorbidities. Ornithine transcarbamylase deficiency presents most commonly with hyperammonemic coma. Although a rare disorder, ornithine transcarbamylase deficiency is the most common of the urea cycle disorders, which can occur both in children, and less commonly, in adults. The urea cycle disorder is usually acquired as an X-linked trait, and very rarely, similar to our reported case, may be acquired as a "new" mutation. Mutations that lead to later-onset presentations may lead to life-threatening disease and may be unrecognized, particularly when the first clinical symptoms occur in adulthood. We report the case of a previously healthy 17-year-old white man who developed a prolonged seizure and a rapid decline in mental status leading to coma over a 3-day period. Analysis of the OTC gene showed a 119G variant, which was identified in exon 2 of the OTC gene by sequencing. A diagnosis of ornithine transcarbamylase deficiency should be considered in adult patients who present with unexplained hyperammonemic coma and for all adult patients presenting with cryptogenic new-onset seizure and laboratory finding of elevated blood ammonia levels. This reported case highlights the importance of early recognition of this potentially reversible cause of life-threatening encephalopathy, as timely recognition and appropriate treatment can be lifesaving.

The Effect of Cisplatin on Blood Ammonia Elevation by Alanyl-Glutamine Supplementation.

PubMed

Obayashi, Yoko; Kajiwara, Kenta; Nakamura, Eiji

2018-01-01

Although there are many clinical studies in which the beneficial effect of glutamine formulation on mucositis induced by chemo/radiotherapy was evaluated, the results are sometimes conflicting with the report of clinical deterioration. Then, we hypothesized that chemotherapy may increase the incidence of hyperammonemia without comparable change of major parameters of hepatic/renal disorder. To verify our hypothesis, we examined the increase in blood ammonia level with 1-h intravenous infusion of alanyl-glutamine on day 1-4 after cisplatin (CDDP) administration in rats and assessed the correlation with hepatic/renal parameters. Hepatic parameters (glutamate-oxaloacetic transaminase [GOT] and glutamic-pyruvic transaminase [GPT]) with CDDP did not change until day 3 and only GOT increased on day 4. Renal parameters (plasma creatinine, blood urea nitrogen) with CDDP continuously increased up to day 4. Alanyl-glutamine infusion significantly elevated blood ammonia level of CDDP rats with the peak on day 3, although the same dose did not change that of control rats. These results indicates that CDDP enhances the increase in blood ammonia level by glutamine supplementation without correlating with primary parameters for hepatic/renal dysfunction. © 2018 S. Karger AG, Basel.

Selenium nanoparticles involve HSP-70 and SIRT1 in preventing the progression of type 1 diabetic nephropathy.

PubMed

Kumar, Goru Santosh; Kulkarni, Apoorva; Khurana, Amit; Kaur, Jasmine; Tikoo, Kulbhushan

2014-11-05

The present study was undertaken to examine the protective effect of selenium nanoparticles (SeNPs) in the progression of diabetic nephropathy (DN). Diabetes was induced in male Sprague Dawley (SD) rats by injecting streptozotocin (STZ) (55mg/kg, i.p). DN was then assessed by measuring blood urea nitrogen (BUN), creatinine, albumin, fibronectin and collagen. Changes in the expression of cytoprotective and apoptotic proteins in the kidney of rats were also examined. Herein we show that SeNPs effectively lowered the levels of BUN, creatinine, fibronectin and collagen and elevated the levels of albumin in diabetic rats. Histological observation corroborated with the above protective effects of SeNPs. Interestingly, SeNPs elevated the levels of heat shock protein (HSP-70), longevity protein SIRT 1 and also modulated apoptotic proteins Bax and Bcl-2 in diabetic kidney. Our data represents a paradigm shift in our understanding about the therapeutic potential of SeNPs in preventing DN by not only quenching oxidative stress but also by activating cyto-protective protein HSP70 and longevity protein SIRT1. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Economic value of urea-treated straw fed to lactating buffaloes during the dry season in Nepal.

PubMed

Chemjong, P B

1991-08-01

An experiment was conducted to study the effects of feeding urea-treated rice straw to lactating buffaloes in the Koshi Hills. Six pairs of similar buffaloes on farms were selected. All were given a conventional diet based on rice straw for four weeks, then one of each pair was given 15 to 20 kg/day of urea-treated rice straw for a period of four weeks while the control group received untreated rice straw. In the final four week period all animals were given the conventional diet. Feeding straw treated with 4% urea increased the voluntary intake of straw by 25% and increased milk yield by 1.6 litres/day compared with buffaloes fed the conventional diet containing untreated straw. Milk production remained elevated after the four-week treatment period had finished. The results show that buffalo cows fed urea-treated straw achieved better weight gain, and milk yield increased significantly (P less than 0.01) compared with the control animals. During the treatment period the net benefit was 4.0 (i.e. US$1.16) Nepalese currency rupees (NCRs) per day and the incremental rate of return was 46 per cent. Moreover, in the four weeks following the treatment period the net benefit was 10.0 NCRs (i.e. US$0.40) per day. Ensiling rice straw with 4% urea can be recommended as a safe, economical and suitable method for improving the nutritional value of rice straw on small farms in Nepal thus increasing milk production and liveweight of lactating buffaloes. The practice of feeding urea-treated straw is economic for farmers during the dry season from January to April.(ABSTRACT TRUNCATED AT 250 WORDS)

Ethyl Carbamate Formation Regulated by Lactic Acid Bacteria and Nonconventional Yeasts in Solid-State Fermentation of Chinese Moutai-Flavor Liquor.

PubMed

Du, Hai; Song, Zhewei; Xu, Yan

2018-01-10

This study aimed to identify specific microorganisms related to the formation of precursors of EC (ethyl carbamate) in the solid-state fermentation of Chinese Moutai-flavor liquor. The EC content was significantly correlated with the urea content during the fermentation process (R 2 = 0.772, P < 0.01). Differences in urea production and degradation were found at both species and functional gene levels by metatranscriptomic sequencing and culture-dependent analysis. Lactobacillus spp. could competitively degrade arginine through the arginine deiminase pathway with yeasts, and most Lactobacillus species were capable of degrading urea. Some dominant nonconventional yeasts, such as Pichia, Schizosaccharomyces, and Zygosaccharomyces species, were shown to produce low amounts of urea relative to Saccharomyces cerevisiae. Moreover, unusual urea degradation pathways (urea carboxylase, allophanate hydrolase, and ATP-independent urease) were identified. Our results indicate that EC precursor levels in the solid-state fermentation can be controlled using lactic acid bacteria and nonconventional yeasts.

Use of urea and creatinine levels in vaginal fluid for the diagnosis of preterm premature rupture of membranes and delivery interval after membrane rupture.

PubMed

Gezer, Cenk; Ekin, Atalay; Golbasi, Ceren; Kocahakimoglu, Ceysu; Bozkurt, Umit; Dogan, Askin; Solmaz, Ulaş; Golbasi, Hakan; Taner, Cuneyt Eftal

2017-04-01

To determine whether urea and creatinine measurements in vaginal fluid could be used to diagnose preterm premature rupture of membranes (PPROM) and predict delivery interval after PPROM. A prospective study conducted with 100 pregnant women with PPROM and 100 healthy pregnant women between 24 + 0 and 36 + 6 gestational weeks. All patients underwent sampling for urea and creatinine concentrations in vaginal fluid at the time of admission. Receiver operator curve analysis was used to determine the cutoff values for the presence of PPROM and delivery within 48 h after PPROM. In multivariate logistic regression analysis, vaginal fluid urea and creatinine levels were found to be significant predictors of PPROM (p < 0.001 and p < 0.001, respectively) and delivery within 48 h after PPROM (p = 0.012 and p = 0.017, respectively). The optimal cutoff values for the diagnosis of PPROM were >6.7 mg/dl for urea and >0.12 mg/dl for creatinine. The optimal cutoff values for the detection of delivery within 48 h were >19.4 mg/dl for urea and >0.23 mg/dl for creatinine. Measurement of urea and creatinine levels in vaginal fluid is a rapid and reliable test for diagnosing and also for predicting delivery interval after PPROM.

Responses to dehydration in the one-humped camel and effects of blocking the renin-angiotensin system.

PubMed

Ali, Mahmoud Alhaj; Adem, Abdu; Chandranath, Irwin S; Benedict, Sheela; Pathan, Javed Y; Nagelkerke, Nicolas; Nyberg, Fred; Lewis, Lynley K; Yandle, Tim G; Nicholls, Gary M; Frampton, Chris M; Kazzam, Elsadig

2012-01-01

Our objectives were to compare the levels of circulating electrolytes, hormones, and renal function during 20 days of dehydration in camels versus the level in non-dehydrated camels and to record the effect of blocking angiotensin II AT1 receptors with losartan during dehydration. Dehydration induced significant increments in serum sodium, creatinine, urea, a substantial fall in body weight, and a doubling in plasma arginine vasopressin (AVP) levels. Plasma aldosterone, however, was unaltered compared with time-matched controls. Losartan significantly enhanced the effect of dehydration to reduce body weight and increase serum levels of creatinine and urea, whilst also impairing the rise in plasma AVP and reducing aldosterone levels. We conclude that dehydration in the camel induces substantial increments in serum sodium, creatinine, urea and AVP levels; that aldosterone levels are altered little by dehydration; that blockade of angiotensin II type 1 receptors enhances the dehydration-induced fall in body weight and increase in serum creatinine and urea levels whilst reducing aldosterone and attenuating the rise in plasma AVP.

Responses to Dehydration in the One-Humped Camel and Effects of Blocking the Renin-Angiotensin System

PubMed Central

Ali, Mahmoud Alhaj; Adem, Abdu; Chandranath, Irwin S.; Benedict, Sheela; Pathan, Javed Y.; Nagelkerke, Nicolas; Nyberg, Fred; Lewis, Lynley K.; Yandle, Tim G.; Nicholls, Gary M.; Frampton, Chris M.; Kazzam, Elsadig

2012-01-01

Our objectives were to compare the levels of circulating electrolytes, hormones, and renal function during 20 days of dehydration in camels versus the level in non-dehydrated camels and to record the effect of blocking angiotensin II AT1 receptors with losartan during dehydration. Dehydration induced significant increments in serum sodium, creatinine, urea, a substantial fall in body weight, and a doubling in plasma arginine vasopressin (AVP) levels. Plasma aldosterone, however, was unaltered compared with time-matched controls. Losartan significantly enhanced the effect of dehydration to reduce body weight and increase serum levels of creatinine and urea, whilst also impairing the rise in plasma AVP and reducing aldosterone levels. We conclude that dehydration in the camel induces substantial increments in serum sodium, creatinine, urea and AVP levels; that aldosterone levels are altered little by dehydration; that blockade of angiotensin II type 1 receptors enhances the dehydration-induced fall in body weight and increase in serum creatinine and urea levels whilst reducing aldosterone and attenuating the rise in plasma AVP. PMID:22624009

[Pathogenetic mechanisms of action of tarry substances and Mycobacterium tuberculosis in guinea pigs and rats].

PubMed

Pavlov, V A; Sabadash, E V; Fadina, O V; Mironova, A L

2002-01-01

Harmful environmental agents [polycyclic aromatic hydrocarbons (PAH)] have been ascertained to greatly stimulate the biosynthesis of arginine and urea and reduce the amount of sulfur-containing metabolites in the liver of experimental animals by increasing the level of sulfur sulfate. Against this background, contamination with Mycobacteria tuberculosis (MBT) inhibits the activity of arginine and drastically decreases its amount by elevating the concentration of sulfur-containing metabolites. The supplementary administration of sodium glutamate to animals receiving PAH and MBT potentiates a decrease in nitrogen-rich metabolites and increases the level of sulfur-containing metabolites guinea pigs, tuberculosis resistance being on the rise. Under the influence of a combined action of PAH and MBT, the mutagenic effect of the former lowered in rats.

Urea retranslocation from senescing Arabidopsis leaves is promoted by DUR3-mediated urea retrieval from leaf apoplast

PubMed Central

Bohner, Anne; Kojima, Soichi; Hajirezaei, Mohammad; Melzer, Michael; von Wirén, Nicolaus

2015-01-01

In plants, urea derives either from root uptake or protein degradation. Although large quantities of urea are released during senescence, urea is mainly seen as a short-lived nitrogen (N) catabolite serving urease-mediated hydrolysis to ammonium. Here, we investigated the roles of DUR3 and of urea in N remobilization. During natural leaf senescence urea concentrations and DUR3 transcript levels showed a parallel increase with senescence markers like ORE1 in a plant age- and leaf age-dependent manner. Deletion of DUR3 decreased urea accumulation in leaves, whereas the fraction of urea lost to the leaf apoplast was enhanced. Under natural and N deficiency-induced senescence DUR3 promoter activity was highest in the vasculature, but was also found in surrounding bundle sheath and mesophyll cells. An analysis of petiole exudates from wild-type leaves revealed that N from urea accounted for >13% of amino acid N. Urea export from senescent leaves further increased in ureG-2 deletion mutants lacking urease activity. In the dur3 ureG double insertion line the absence of DUR3 reduced urea export from leaf petioles. These results indicate that urea can serve as an early metabolic marker for leaf senescence, and that DUR3-mediated urea retrieval contributes to the retranslocation of N from urea during leaf senescence. PMID:25440717

INCREASED SERUM LEVELS OF UREA AND CREATININE ARE SURROGATE MARKERS FOR DISRUPTION OF RETINAL PHOTORECEPTOR EXTERNAL LIMITING MEMBRANE AND INNER SEGMENT ELLIPSOID ZONE IN TYPE 2 DIABETES MELLITUS.

PubMed

Saxena, Sandeep; Ruia, Surabhi; Prasad, Senthamizh; Jain, Astha; Mishra, Nibha; Natu, Shankar M; Meyer, Carsten H; Gilhotra, Jagjit S; Kruzliak, Peter; Akduman, Levent

2017-02-01

To evaluate the role of serum urea and creatinine as surrogate markers for disruption of retinal photoreceptor external limiting membrane (ELM) and inner segment ellipsoid zone (EZ) in Type 2 diabetic retinopathy (DR) using spectral-domain optical coherence tomography, for the first time. One hundred and seventeen consecutive cases of Type 2 diabetes mellitus (diabetes without retinopathy [No DR; n = 39], nonproliferative diabetic retinopathy [NPDR; n = 39], proliferative diabetic retinopathy [PDR; n = 39]) and 40 healthy control subjects were included. Serum levels of urea and creatinine were assessed using standard protocol. Spectral-domain optical coherence tomography was used to grade the disruption of ELM and EZ as follows: Grade 0, no disruption of ELM and EZ; Grade 1, ELM disrupted, EZ intact; Grade 2, ELM and EZ disrupted. Data were analyzed statistically. Increase in serum levels of urea (F = 22.93) and creatinine (F = 15.82) and increased grades of disruption of ELM and EZ (γ = 116.3) were observed with increased severity of DR (P < 0.001). Increase in serum levels of urea (F = 10.45) and creatinine (F = 6.89) was observed with increased grades of disruption of ELM and EZ (P = 0.001). Serum levels of urea and creatinine are surrogate markers for disruption of retinal photoreceptor ELM and EZ on spectral-domain optical coherence tomography in DR.

Distributional shift of urea production site from the extraembryonic yolk sac membrane to the embryonic liver during the development of cloudy catshark (Scyliorhinus torazame).

PubMed

Takagi, Wataru; Kajimura, Makiko; Tanaka, Hironori; Hasegawa, Kumi; Ogawa, Shuntaro; Hyodo, Susumu

2017-09-01

Urea is an essential osmolyte for marine cartilaginous fishes. Adult elasmobranchs and holocephalans are known to actively produce urea in the liver, muscle and other extrahepatic organs; however, osmoregulatory mechanisms in the developing cartilaginous fish embryo with an undeveloped urea-producing organ are poorly understood. We recently described the contribution of extraembryonic yolk sac membranes (YSM) to embryonic urea synthesis during the early developmental period of the oviparous holocephalan elephant fish (Callorhinchus milii). In the present study, to test whether urea production in the YSM is a general phenomenon among oviparous Chondrichthyes, we investigated gene expression and activities of ornithine urea cycle (OUC) enzymes together with urea concentrations in embryos of the elasmobranch cloudy catshark (Scyliorhinus torazame). The intracapsular fluid, in which the catshark embryo develops, had a similar osmolality to seawater, and embryos maintained a high concentration of urea at levels similar to that of adult plasma throughout development. Relative mRNA expressions and activities of catshark OUC enzymes were significantly higher in YSM than in embryos until stage 32. Concomitant with the development of the embryonic liver, the expression levels and activities of OUC enzymes were markedly increased in the embryo from stage 33, while those of the YSM decreased from stage 32. The present study provides further evidence that the YSM contributes to embryonic urea homeostasis until the liver and other extrahepatic organs become fully functional, and that urea-producing tissue shifts from the YSM to the embryonic liver in the late developmental period of oviparous marine cartilaginous fishes. Copyright © 2017 Elsevier Inc. All rights reserved.

Investigation of hypoglycemic, hypolipidemic and antioxidant activities of aqueous extract of Terminalia paniculata bark in diabetic rats

PubMed Central

Ramachandran, Subramaniam; Rajasekaran, Aiyalu; Manisenthilkumar, KT

2012-01-01

Objective To investigate the hypoglycemic, hypolipidemic and antioxidant activities of aqueous extract of Terminalia paniculata bark (AETPB) in streptozotocin (STZ)-induced diabetic rats. Methods Acute toxicity was studied in rats after the oral administration of AETPB to determine the dose to assess hypoglycemic activity. In rats, diabetes was induced by injection of STZ (60 mg/kg, i.p.) and diabetes was confirmed 72 h after induction, and then allowed for 14 days to stabilize blood glucose level. In diabetic rats, AETPB was orally given for 28 days and its effect on blood glucose and body weight was determined on a weekly basis. At the end of the experimental day, fasting blood sample was collected to estimate the haemoglobin (Hb), glycosylated haemoglobin (HbA1c), serum creatinine, urea, serum glutamate-pyruvate transaminase (SGPT), serum glutamate-oxaloacetate transaminase (SGOT) and insulin levels. The liver and kidney were collected to determine antioxidants levels in diabetic rats. Results Oral administration of AETPB did not exhibit toxicity and death at a dose of 2 000 mg/kg. AETPB treated diabetic rats significantly (P<0.001, P<0.01 and P<0.05) reduced elevated blood glucose, HbA1c, creatinine, urea, SGPT and SGOT levels when compared with diabetic control rats. The body weight, Hb, insulin and total protein levels were significantly (P<0.001, P<0.01 and P<0.05) increased in diabetic rats treated with AETPB compared to diabetic control rats. In diabetic rats, AETPB treatment significantly reversed abnormal status of antioxidants and lipid profile levels towards near normal levels compared to diabetic control rats. Conclusions Present study results confirm that AETPB possesses significant hypoglycemic, hypolipidemic and antioxidant activities in diabetic condition. PMID:23569911

Effects of supplemental energy and protein on forage digestion and urea kinetics in growing beef cattle.

PubMed

Bailey, E A; Titgemeyer, E C; Olson, K C; Brake, D W; Jones, M L; Anderson, D E

2012-10-01

Effects of supplemental energy sources on nutrient digestion and urea kinetics at 2 levels of degradable intake protein were evaluated in cattle (Bos taurus). Six ruminally and duodenally cannulated steers (208 ± 17 kg) were used in a 6 × 6 Latin square with treatments arranged as a 3 × 2 factorial. Energy treatments included a control, 600 g glucose dosed ruminally once daily, and 480 g VFA infused ruminally over 8 h daily. Casein (120 or 240 g) was dosed ruminally once daily. Steers had ad libitum access to prairie hay (5.8% CP). Jugular infusion of (15)N(15)N-urea with measurement of enrichment in urine was used to measure urea kinetics. Infusing VFA decreased (P < 0.01) forage intake by 27%. Supplementing glucose decreased (P < 0.01) total tract NDF digestibility and tended to decrease ruminal NDF digestibility; depressions in response to glucose tended to be greater at the lower level of casein. Increasing casein decreased (P < 0.02) ruminal pH. Infusing VFA decreased pH only during infusions, whereas glucose decreased pH 2 h after dosing. Ruminal concentrations of NH(3), acetate, and propionate decreased and butyrate concentration increased when glucose was supplemented. Increasing casein supplementation increased (P < 0.01) ruminal concentrations of NH(3), acetate, and propionate. Supplemental energy decreased (P = 0.03) plasma urea-N concentration, but casein level did not affect it (P = 0.16). Microbial N flow was greater (P < 0.04) for 240 than for 120 g/d casein but was not affected by supplemental energy (P = 0.23). Urea-N entry rate and gut entry of urea-N were not affected (P ≥ 0.12) by supplemental energy or casein, but the proportion of urea production that was recycled to the gut was less (P = 0.01) when 240 g/d rather than 120 g/d casein was provided. Compared with VFA, glucose tended (P = 0.07) to increase the proportion of urea-N entry rate that was recycled to the gut. Supplementation with glucose led to more (P = 0.01) microbial uptake of recycled urea than did supplementation with VFA. Urea recycling did not differ greatly among treatments despite impacts on ruminal pH and NH(3) and on plasma urea-N that were expected to alter urea transport across ruminal epithelium. Lack of treatment effects on urea production indicate that the complete diets did not provide excessive amounts of N and that increases of intestinally available AA were used efficiently by cattle for protein deposition.

Urea and ammonia excretion into gastric juice in regularly dialyzed patients and patients after renal transplantation. I. Dialyzed patients.

PubMed

Skála, I; Marecková, O; Růzicková, J; Bláha, J; Straková, M; Reneltová, I; Jirka, J; Kocandrle, V; Zvolánková, K

1978-01-01

In regularly dialyzed patients in basal gastric juice and after stimulation with pentagastrin the volume of titrable acidity, urea and ammonia were assessed. It was revealed that in relation to the plasma urea concentration in basal juice the mean urea and ammonia concentration is roughly half and in stimulation juice roughly one third. The urea concentration in gastric juice is negatively correlated to the ammonia concentration. Urea excretion into the stomach depends on the plasma urea level and on the secretory gastric activity. The decisive factor of gastric secretion is probably parietal cell secretion. From the results ensues that gastric juice of dialyzed patients contains a quantitatively significant amount of urea and ammonia. Ammonia due to its neutralizing action distorts the examination of gastric acidity assessed by titration. The findings call for a revision of hitherto known data concerning gastric secretion of uraemic patients.

Extracellular vesicles from human liver stem cells restore argininosuccinate synthase deficiency.

PubMed

Herrera Sanchez, Maria Beatriz; Previdi, Sara; Bruno, Stefania; Fonsato, Valentina; Deregibus, Maria Chiara; Kholia, Sharad; Petrillo, Sara; Tolosano, Emanuela; Critelli, Rossana; Spada, Marco; Romagnoli, Renato; Salizzoni, Mauro; Tetta, Ciro; Camussi, Giovanni

2017-07-27

Argininosuccinate synthase (ASS)1 is a urea cycle enzyme that catalyzes the conversion of citrulline and aspartate to argininosuccinate. Mutations in the ASS1 gene cause citrullinemia type I, a rare autosomal recessive disorder characterized by neonatal hyperammonemia, elevated citrulline levels, and early neonatal death. Treatment for this disease is currently restricted to liver transplantation; however, due to limited organ availability, substitute therapies are required. Recently, extracellular vesicles (EVs) have been reported to act as intercellular transporters carrying genetic information responsible for cell reprogramming. In previous studies, we isolated a population of stem cell-like cells known as human liver stem cells (HLSCs) from healthy liver tissue. Moreover, EVs derived from HLSCs were reported to exhibit regenerative effects on the liver parenchyma in models of acute liver injury. The aim of this study was to evaluate whether EVs derived from normal HLSCs restored ASS1 enzymatic activity and urea production in hepatocytes differentiated from HLSCs derived from a patient with type I citrullinemia. HLSCs were isolated from the liver of a patient with type I citrullinemia (ASS1-HLSCs) and characterized by fluorescence-activated cell sorting (FACS), immunofluorescence, and DNA sequencing analysis. Furthermore, their differentiation capabilities in vitro were also assessed. Hepatocytes differentiated from ASS1-HLSCs were evaluated by the production of urea and ASS enzymatic activity. EVs derived from normal HLSCs were purified by differential ultracentrifugation followed by floating density gradient. The EV content was analyzed to identify the presence of ASS1 protein, mRNA, and ASS1 gene. In order to obtain ASS1-depleted EVs, a knockdown of the ASS1 gene in HLSCs was performed followed by EV isolation from these cells. Treating ASS1-HLSCs with EVs from HLSCs restored both ASS1 activity and urea production mainly through the transfer of ASS1 enzyme and mRNA. In fact, EVs from ASS1-knockdown HLSCs contained low amounts of ASS1 mRNA and protein, and were unable to restore urea production in hepatocytes differentiated from ASS1-HLSCs. Collectively, these results suggest that EVs derived from normal HLSCs may compensate the loss of ASS1 enzyme activity in hepatocytes differentiated from ASS1-HLSCs.

Serum sodium concentration, blood urea nitrogen, and outcomes in patients hospitalized for acute decompensated heart failure.

PubMed

Kajimoto, Katsuya; Minami, Yuichiro; Sato, Naoki; Takano, Teruo

2016-11-01

This study investigated the association of a low serum sodium and elevated blood urea nitrogen (BUN) with outcomes in acute decompensated heart failure (HF) patients. Of the 4842 patients enrolled in the Acute Decompensated Heart Failure Syndromes (ATTEND) registry, 4438 patients discharged after hospitalization for acute decompensated HF were investigated to assess the association of a low serum sodium and/or elevated BUN at discharge with all-cause mortality. The patients were divided into four groups based on serum sodium (>136 or ≤136mEq/l) and BUN (<25 or ≥25mg/dl) at discharge. The median follow-up period after discharge was 517 (381-776) days. According to multivariate analysis, a low serum sodium (≤136mEq/l) or an elevated BUN (≥25mg/dl) was significantly associated with a higher risk of all-cause death compared with patients who had neither (hazard ratio [HR], 1.53; 95% confidence interval [CI], 1.22 to 1.94; P<0.001 and HR, 1.44; 95% CI, 1.19 to 1.73; P<0.001, respectively). Patients with both low serum sodium and elevated BUN had a higher risk of all-cause death relative to patients with neither (HR, 2.64; 95% CI, 2.17 to 3.20; P<0.001) and also relative to patients with either low serum sodium alone or elevated BUN alone (HR, 1.72; 95% CI, 1.36 to 2.18; P<0.001 and HR, 1.84; 95% CI, 1.53 to 2.21; P<0.001, respectively). These findings demonstrated that a low serum sodium and an elevated BUN may be additive risk factors for postdischarge mortality in acute decompensated HF patients. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Hematologic and biochemical characteristics of stranded green sea turtles.

PubMed

March, Duane T; Vinette-Herrin, Kimberly; Peters, Andrew; Ariel, Ellen; Blyde, David; Hayward, Doug; Christidis, Les; Kelaher, Brendan P

2018-05-01

To improve understanding of pathophysiologic processes occurring in green sea turtles ( Chelonia mydas) stranded along the east coast of Australia, we retrospectively examined the hematologic and biochemical blood parameters of 127 green turtles admitted to 2 rehabilitation facilities, Dolphin Marine Magic (DMM) and Taronga Zoo (TZ), between 2002 and 2016. The predominant size class presented was small immature animals (SIM), comprising 88% and 69% of admissions to DMM and TZ, respectively. Significant differences in blood profiles were noted between facility, size, and outcome. Elevated levels of aspartate aminotransferase (AST) and heterophils were poor prognostic indicators in animals from TZ, but not DMM. SIM animals at both institutions had lower protein levels than large older (LO) animals. SIM animals at DMM also had lower hematocrit and monocyte concentration; SIM animals at TZ had lower heterophil counts. Urea was measured for 27 SIM animals from TZ, but the urea-to-uric acid ratio was not prognostically useful. Strong correlations were seen between AST and glutamate dehydrogenase (GDH; r = 0.68) and uric acid and bile acids ( r = 0.72) in the 45 SIM animals from DMM in which additional analytes were measured. χ 2 contingency tests showed that the most recently published reference intervals were not prognostically useful. A paired t-test showed that protein levels rose and heterophil numbers fell in the 15 SIM animals from TZ during the rehabilitation process. Our results indicate that further work is required to identify reliable prognostic biomarkers for green turtles.

Renoprotective effect of the isoflavonoid biochanin A against cisplatin induced acute kidney injury in mice: Effect on inflammatory burden and p53 apoptosis.

PubMed

Suliman, Faiha A; Khodeer, Dina M; Ibrahiem, Afaf; Mehanna, Eman T; El-Kherbetawy, Mohamed K; Mohammad, Hala M F; Zaitone, Sawsan A; Moustafa, Yasser M

2018-05-21

Cisplatin is a potent widely-used chemotherapeutics; however, its clinical use is associated with nephrotoxicity. Renoprotective approaches are being discovered to halt the tubular cell death due to inflammatory and apoptotic burdens. In the present study, the renoprotective effects of different doses of biochanin A (10, 20 or 40 mg/kg) in mice treated with a single injection of cisplatin (10 mg/kg) were reported. Cisplatin administration resulted in marked increases in serum creatinine and blood urea nitrogen. Further, renal homogenates showed increased level of inflammatory cytokines and upregulation of the expression of p53 up-regulated modulator of apoptosis (PUMA), p53 and caspase 3 but downregulation in Nrf2 expression. Furthermore, cisplatin group showed marked necrosis and degenerated tubular lining epithelial cells with frequently detected apoptotic bodies. Mice treated with biochanin A (10, 20 or 40 mg/kg) for 14 days prior to cisplatin abrogated cisplatin-mediated damage. Furthermore, the elevated serum creatinine and urea levels were lessened by some doses of biochanin A, indicating protection against renal injury. Similarly, the changes in apoptosis and inflammatory markers have ameliorated to significant levels (P < 0.05). The results suggest biochanin A as a nephroprotective agent against cisplatin toxicity. Overall, this nephroprotective effect of biochanin A involved anti-inflammatory and antiapoptotic activities. Copyright © 2018 Elsevier B.V. All rights reserved.

Resistance to acetohydroxamate acquired by slow adaptive increases in urease in cultured tobacco cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yamaya, T.; Filner, P.

1981-06-01

Urease activity of tobacco XD cells (1U cells) had undergone a 4-fold increase (4U cells) during a year of growth on urea. A clone of 4U cells gave rise to 12U cells during another year of growth on urea. The doubling time of 12U cells on urea is 2.2 days, compared to about 4 days for 1U cells, while 1U and 12U cells double in 2 days on nitrate. Acetohydroxamic acid (AHA), a specific inhibitor/reversible inactivator of jack bean urease, affects tobacco cells urease similarly. Fifty per cent inhibition of growth by AHA occurred at 20 micromolar in 1U cellsmore » growing on urea and at 165 micromolar in 12U cells growing on urea, but at 600 micromolar for either 1U or 12U cells growing on nitrate. When 12U cells were grown on urea with 100 micromolar AHA, extractable urease activity decreased 80% within 2.5 hours and remained at this level for 2 weeks; the doubling time increased to 3.7 days, and intracellular urea rose 2-fold, compared to 12U cells grown on urea without AHA. Urease of 12U cells inactivated by AHA in vivo could be reactivated to its pre-AHA level by incubation at 30 C after extraction and separation from free AHA. AHA inhibited incorporation of /sup 15/N from (/sup 15/N) urea into Kjeldahl nitrogen in the cells, in spite of the increased intracellular urea. These results indicate that AHA acts primarily by inhibiting urease action, rather than by inhibition of formation of urease protein or of uptake of urea. Because 12U cells are 8 times more tolerant of AHA than 1U cells, it is likely that growth on urea in the presence of AHA should select strongly for cells with high urease.« less

Dynamics of a pasture soil microbial community after deposition of cattle urine amended with [13C]urea.

PubMed

Petersen, Søren O; Roslev, Peter; Bol, Roland

2004-11-01

Within grazed pastures, urine patches are hot spots of nitrogen turnover, since dietary N surpluses are excreted mainly as urea in the urine. This short-term experiment investigated 13C uptake in microbial lipids after simulated deposition of cattle urine at 10.0 and 17.1 g of urea C m(-2). Confined field plots without or with cattle urine amendment were sampled after 4 and 14 days, and soil from 0- to 5-cm and 10- to 20-cm depths was analyzed for content and composition of phospholipid fatty acids (PLFAs) and for the distribution of urea-derived 13C among individual PLFAs. Carbon dioxide emissions were quantified, and the contributions derived from urea were assessed. Initial changes in PLFA composition were greater at the lower level of urea, as revealed by a principal-component analysis. At the higher urea level, osmotic stress was indicated by the dynamics of cyclopropane fatty acids and branched-chain fatty acids. Incorporation of 13C from [13C]urea was low but significant, and the largest amounts of urea-derived C were found in common fatty acids (i.e., 16:0, 16:1omega7c, and 18:1omega7) that would be consistent with growth of typical NH4(+)-oxidizing (Nitrosomonas) and NO2(-)-oxidizing (Nitrobacter) bacteria. Surprisingly, a 20 per thousand depletion of 13C in the cyclopropane fatty acid cy17:0 was observed after 4 days, which was replaced by a 10 to 20 per thousand depletion of that in cy19:0 after 14 days. Possible reasons for this pattern are discussed. Autotrophic nitrifiers could not be implicated in urea hydrolysis to any large extent, but PLFA dynamics and the incorporation of urea-derived 13C in PLFAs indicated a response of nitrifiers which differed between the two urea concentrations.

Dynamics of a Pasture Soil Microbial Community after Deposition of Cattle Urine Amended with [13C]Urea

PubMed Central

Petersen, Søren O.; Roslev, Peter; Bol, Roland

2004-01-01

Within grazed pastures, urine patches are hot spots of nitrogen turnover, since dietary N surpluses are excreted mainly as urea in the urine. This short-term experiment investigated 13C uptake in microbial lipids after simulated deposition of cattle urine at 10.0 and 17.1 g of urea C m−2. Confined field plots without or with cattle urine amendment were sampled after 4 and 14 days, and soil from 0- to 5-cm and 10- to 20-cm depths was analyzed for content and composition of phospholipid fatty acids (PLFAs) and for the distribution of urea-derived 13C among individual PLFAs. Carbon dioxide emissions were quantified, and the contributions derived from urea were assessed. Initial changes in PLFA composition were greater at the lower level of urea, as revealed by a principal-component analysis. At the higher urea level, osmotic stress was indicated by the dynamics of cyclopropane fatty acids and branched-chain fatty acids. Incorporation of 13C from [13C]urea was low but significant, and the largest amounts of urea-derived C were found in common fatty acids (i.e., 16:0, 16:1ω7c, and 18:1ω7) that would be consistent with growth of typical NH4+-oxidizing (Nitrosomonas) and NO2−-oxidizing (Nitrobacter) bacteria. Surprisingly, a 20‰ depletion of 13C in the cyclopropane fatty acid cy17:0 was observed after 4 days, which was replaced by a 10 to 20‰ depletion of that in cy19:0 after 14 days. Possible reasons for this pattern are discussed. Autotrophic nitrifiers could not be implicated in urea hydrolysis to any large extent, but PLFA dynamics and the incorporation of urea-derived 13C in PLFAs indicated a response of nitrifiers which differed between the two urea concentrations. PMID:15528493

Kidney function and plasma copeptin levels in healthy kidney donors and autosomal dominant polycystic kidney disease patients.

PubMed

Zittema, Debbie; van den Berg, Else; Meijer, Esther; Boertien, Wendy E; Muller Kobold, Anneke C; Franssen, Casper F M; de Jong, Paul E; Bakker, Stephan J L; Navis, Gerjan; Gansevoort, Ron T

2014-09-05

Plasma copeptin, a marker of arginine vasopressin, is elevated in patients with autosomal dominant polycystic kidney disease and predicts disease progression. It is unknown whether elevated copeptin levels result from decreased kidney clearance or as compensation for impaired concentrating capacity. Data from patients with autosomal dominant polycystic kidney disease and healthy kidney donors before and after donation were used, because after donation, overall GFR decreases with a functionally normal kidney. Data were obtained between October of 2008 and January of 2012 from healthy kidney donors who visited the institution for routine measurements predonation and postdonation and patients with autosomal dominant polycystic kidney disease who visited the institution for kidney function measurement. Plasma copeptin levels were measured using a sandwich immunoassay, GFR was measured as (125)I-iothalamate clearance, and urine concentrating capacity was measured as urine-to-plasma ratio of urea. In patients with autosomal dominant polycystic kidney disease, total kidney volume was measured with magnetic resonance imaging. Patients with autosomal dominant polycystic kidney disease (n=122, age=40 years, men=56%) had significantly higher copeptin levels (median=6.8 pmol/L; interquartile range=3.4-15.7 pmol/L) compared with donors (n=134, age=52 years, men=49%) both predonation and postdonation (median=3.8 pmol/L; interquartile range=2.8-6.3 pmol/L; P<0.001; median=4.4 pmol/L; interquartile range=3.6-6.1 pmol/L; P<0.001). In donors, copeptin levels did not change after donation, despite a significant fall in GFR (from 105 ± 17 to 66 ± 10; P<0.001). Copeptin and GFR were significantly associated in patients with autosomal dominant polycystic kidney disease (β=-0.45, P<0.001) but not in donors. In patients with autosomal dominant polycystic kidney disease, GFR and total kidney volume were both associated significantly with urine-to-plasma ratio of urea (β=0.84, P<0.001; β=-0.51, P<0.001, respectively). On the basis of the finding in donors that kidney clearance is not a main determinant of plasma copeptin levels, it was hypothesized that, in patients with autosomal dominant polycystic kidney disease, kidney damage and associated impaired urine concentration capacity determine copeptin levels. Copyright © 2014 by the American Society of Nephrology.

Renal Response to Chronic Centrifugation in Rats

NASA Technical Reports Server (NTRS)

Ortiz, Rudy M.; Wang, T. J.; Corbin, B. J.; Wade, C. E.; Hargens, Alan R. (Technical Monitor)

1996-01-01

Previously reported effects of chronic centrifugation on renal function in mammals are contradictory. The present study was conducted as an effort to provide a comprehensive analysis of renal response to chronic centrifugation (12 days at +2 Gz). Sixteen male Sprague-Dawley rats (210-230 g) were used: eight centrifuged (EC) and eight off centrifuge controls (OCC). During centrifugation EC had lower body weight and food consumption. EC showed a decrease (72%) in water intake for the first two days (T1 and T2) followed by significant increases from T4-T6. EC urine output increased two-fold over the first four days, returning to baseline by T9. EC urea excretion was elevated on T3 through T5. Creatinine, Na(+), K(+), and osmolar excretion were lower than OCC over the last four days of the study. Assuming constant plasma osmolarity and creatinine levels, EC free water clearance (C(sub H2O)) was elevated significantly on T4 when the peak urine output was exhibited. EC also had a greater C(sub H2O) over the last four days, associated with a significantly lower osmolar clearance and GFR. The initial diuresis exhibited during centrifugation can be attributed to a reduced water resorption and increased urea excretion. This diuresis was mediated independent of changes in GFR over the first eight days. However, differences in excretion seen after eight days of centrifugation are probably GFR mediated which would imply animals established a new homeostatic setpoint by that time. Centrifugation elicites an acute alteration in fluid homeostasis followed by adaptation within a week.

Urea uptake enhances barrier function and antimicrobial defense in humans by regulating epidermal gene expression

PubMed Central

Grether-Beck, Susanne; Felsner, Ingo; Brenden, Heidi; Kohne, Zippora; Majora, Marc; Marini, Alessandra; Jaenicke, Thomas; Rodriguez-Martin, Marina; Trullas, Carles; Hupe, Melanie; Elias, Peter M.; Krutmann, Jean

2012-01-01

Urea is an endogenous metabolite, known to enhance stratum corneum hydration. Yet, topical urea anecdotally also improves permeability barrier function, and it appears to exhibit antimicrobial activity. Hence, we hypothesized that urea is not merely a passive metabolite, but a small-molecule regulator of epidermal structure and function. In 21 human volunteers, topical urea improved barrier function in parallel with enhanced antimicrobial peptide (LL-37 and β-defensin-2) expression. Urea both stimulates expression of, and is transported into keratinocytes by two urea transporters, UT-A1 and UT-A2, and by aquaporin 3, 7 and 9. Inhibitors of these urea transporters block the downstream biological effects of urea, which include increased mRNA and protein levels for: (i) transglutaminase-1, involucrin, loricrin and filaggrin; (ii) epidermal lipid synthetic enzymes, and (iii) cathelicidin/LL-37 and β-defensin-2. Finally, we explored the potential clinical utility of urea, showing that topical urea applications normalized both barrier function and antimicrobial peptide expression in a murine model of atopic dermatitis (AD). Together, these results show that urea is a small-molecule regulator of epidermal permeability barrier function and antimicrobial peptide expression after transporter uptake, followed by gene regulatory activity in normal epidermis, with potential therapeutic applications in diseased skin. PMID:22418868

Hepatic and renal effects of low concentrations of methoxyflurane in exposed delivery ward personnel

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dahlgren, B.E.

1980-12-01

During five alternating three-week periods either methoxyflurane-nitrous oxide or nitrous oxide alone was used for obstetrical analgesia. Delivery ward personnel were followed by venous blood samples once a week. Analyses of blood urea nitrogen, serum uric acid, SGOT and SGPT showed significantly elevated levels three days after exposure to methoxyflurane. This study demonstrates the importance of the scavenging of anesthetic gases to reduce the exposure of personnel to inhalational agents used in delivery suites. Since definite alterations in the indices of both hepatic and renal functions were recognized in obstetrical personnel following exposure, a re-evaluation of the use of methoxyfluranemore » for obstetrical analgesia is suggested.« less

Temperature dependent Raman spectroscopy of melamine and structural analogs in milk powder

USDA-ARS?s Scientific Manuscript database

Hyperspectral Raman imaging has the potential for rapid screening of solid-phase samples for potential adulterants. We found that the Raman spectra of melamine analogs changed dramatically and uniquely as a function of elevated temperature. Raman spectra were acquired for urea, biuret, cyanuric acid...

Effect of alternative pathway therapy on branched chain amino acid metabolism in urea cycle disorder patients.

PubMed

Scaglia, Fernando; Carter, Susan; O'Brien, William E; Lee, Brendan

2004-04-01

Urea cycle disorders (UCDs) are a group of inborn errors of hepatic metabolism caused by the loss of enzymatic activities that mediate the transfer of nitrogen from ammonia to urea. These disorders often result in life-threatening hyperammonemia and hyperglutaminemia. A combination of sodium phenylbutyrate and sodium phenylacetate/benzoate is used in the clinical management of children with urea cycle defects as a glutamine trap, diverting nitrogen from urea synthesis to alternatives routes of excretion. We have observed that patients treated with these compounds have selective branched chain amino acid (BCAA) deficiency despite adequate dietary protein intake. However, the direct effect of alternative therapy on the steady state levels of plasma branched chain amino acids has not been well characterized. We have measured steady state plasma branched chain and other essential non-branched chain amino acids in control subjects, untreated ornithine transcarbamylase deficiency females and treated null activity urea cycle disorder patients in the fed steady state during the course of stable isotope studies. Steady-state leucine levels were noted to be significantly lower in treated urea cycle disorder patients when compared to either untreated ornithine transcarbamylase deficiency females or control subjects (P<0.0001). This effect was reproduced in control subjects who had depressed leucine levels when treated with sodium phenylacetate/benzoate (P<0.0001). Our studies suggest that this therapeutic modality has a substantial impact on the metabolism of branched chain amino acids in urea cycle disorder patients. These findings suggest that better titration of protein restriction could be achieved with branched chain amino acid supplementation in patients with UCDs who are on alternative route therapy.

Alternative channels for urea in the inner medulla of the rat kidney.

PubMed

Nawata, C Michele; Dantzler, William H; Pannabecker, Thomas L

2015-12-01

The ascending thin limbs (ATLs) and lower descending thin limbs (DTLs) of Henle's loop in the inner medulla of the rat are highly permeable to urea, and yet no urea transporters have been identified in these sections. We hypothesized that novel, yet-unidentified transporters in these tubule segments could explain the high urea permeability. cDNAs encoding for Na(+)-glucose transporter 1a (SGLT1a), Na(+)-glucose transporter 1 (NaGLT1), urea transporter (UT)-A2c, and UT-A2d were isolated and cloned from the Munich-Wistar rat inner medulla. SGLT1a is a novel NH2-terminal truncated variant of SGLT1. NaGLT1 is a Na(+)-dependent glucose transporter primarily located in the proximal tubules and not previously described in the thin limbs. UT-A2c and UT-A2d are novel variants of UT-A2. UT-A2c is truncated at the COOH terminus, and UT-A2d has one exon skipped. When rats underwent water restriction for 72 h, mRNA levels of SGLT1a increased in ATLs, NaGLT1 levels increased in both ATLs and DTLs, and UT-A2c increased in ATLs. [(14)C]urea uptake assays performed on Xenopus oocytes heterologously expressing these proteins revealed that despite having structural differences from their full-length versions, SGLT1a, UT-A2c, and UT-A2d enhanced urea uptake. NaGLT1 also facilitated urea uptake. Uptakes were Na(+) independent and inhibitable by phloretin and/or phloridzin. Our data indicate that there are several alternative channels for urea in the rat inner medulla that could potentially contribute to the high urea permeabilities in thin limb segments. Copyright © 2015 the American Physiological Society.

Alternative channels for urea in the inner medulla of the rat kidney

PubMed Central

Dantzler, William H.; Pannabecker, Thomas L.

2015-01-01

The ascending thin limbs (ATLs) and lower descending thin limbs (DTLs) of Henle's loop in the inner medulla of the rat are highly permeable to urea, and yet no urea transporters have been identified in these sections. We hypothesized that novel, yet-unidentified transporters in these tubule segments could explain the high urea permeability. cDNAs encoding for Na+-glucose transporter 1a (SGLT1a), Na+-glucose transporter 1 (NaGLT1), urea transporter (UT)-A2c, and UT-A2d were isolated and cloned from the Munich-Wistar rat inner medulla. SGLT1a is a novel NH2-terminal truncated variant of SGLT1. NaGLT1 is a Na+-dependent glucose transporter primarily located in the proximal tubules and not previously described in the thin limbs. UT-A2c and UT-A2d are novel variants of UT-A2. UT-A2c is truncated at the COOH terminus, and UT-A2d has one exon skipped. When rats underwent water restriction for 72 h, mRNA levels of SGLT1a increased in ATLs, NaGLT1 levels increased in both ATLs and DTLs, and UT-A2c increased in ATLs. [14C]urea uptake assays performed on Xenopus oocytes heterologously expressing these proteins revealed that despite having structural differences from their full-length versions, SGLT1a, UT-A2c, and UT-A2d enhanced urea uptake. NaGLT1 also facilitated urea uptake. Uptakes were Na+ independent and inhibitable by phloretin and/or phloridzin. Our data indicate that there are several alternative channels for urea in the rat inner medulla that could potentially contribute to the high urea permeabilities in thin limb segments. PMID:26423860

Calcitriol decreases TGF-β1 and angiotensin II production and protects against chlorhexide digluconate-induced liver peritoneal fibrosis in rats.

PubMed

Lee, Chung-Jen; Subeq, Yi-Maun; Lee, Ru-Ping; Liou, Hung-Hsiang; Hsu, Bang-Gee

2014-01-01

Peritoneal fibrosis is a major complication of peritoneal dialysis that can lead to ultrafiltration failure. This study investigates the protective effects of calcitriol on chlorhexidine digluconate-induced peritoneal fibrosis in rats. Peritoneal fibrosis was induced in Sprague-Dawley rats by daily administration of 0.5mL 0.1% chlorhexidine digluconate in normal saline via peritoneal dialysis for 1week. Rats received daily intravenous injections of calcitriol (low-dose, 10ng/kg; or high-dose, 100ng/kg) for 1week. After 7days, conventional 4.25% Dianeal (30mL) was administered via peritoneal dialysis over 4h. Peritoneal solute transport was calculated from the dialysate concentration relative to its concentration in the initial infused dialysis solution (D4/D0 glucose) for glucose, and the dialysate-to-plasma concentration ratio (D4/P4 urea) at 4h for urea. Rats were then sacrificed and the liver peritoneum was harvested for immunohistochemical analysis via microscopy. After dialysis, the D4/P4 Urea level was reduced; increases were observed in the D4/D0 glucose level and the levels of active transforming growth factor-β1 and angiotensin II in serum and dialysate; the liver peritoneum and muscle peritoneum was markedly thickened, and the expression of α-SMA, fibronectin, collagen, vascular endothelial growth factor, angiotensin II, transforming growth factor-β1, and phosphorylated Smad2/3 (P-Smad2/3)-positive cells in the liver peritoneum was elevated in the peritoneal fibrosis group compared with the vehicle group. Calcitriol decreased the serum and dialysate active transforming growth factor-β1 and angiotensin II level, decreased the thickness of the liver peritoneum and muscle peritoneum, and decreased the expression of α-SMA, fibronectin, collagen, vascular endothelial growth factor, angiotensin II, transforming growth factor-β1, and P-Smad2/3-positive cells in liver peritoneum cells. High-dose calcitriol exhibited better protective effects against peritoneal fibrosis than did the lower dose. Calcitriol protected against chlorhexidine digluconate-induced peritoneal fibrosis in rats by decreasing transforming growth factor-β1 and angiotensin II production. Copyright © 2013 Elsevier Ltd. All rights reserved.

Some amino acids levels: glutamine,glutamate, and homocysteine, in plasma of children with chronic kidney disease.

PubMed

Fadel, Fatina I; Elshamaa, Manal F; Essam, Rascha G; Elghoroury, Eman A; El-Saeed, Gamila S M; El-Toukhy, Safinaz E; Ibrahim, Mona Hamed

2014-03-01

The high prevalence of protein-energy malnutrition is a critical issue for patients with chronic kidney disease (CKD). Serum albumin is the most commonly used nutritional marker. Another index is plasma amino acid (AA) profile. Of these, the plasma levels of glutamine, glutamate and homocysteine, correlate well with nutritional status. We measured some plasma AAs in children with different stages CKD to provide information in monitoring the therapeutic strategy, particularly in AA supplementary therapy or protein restriction. Three amino acids were evaluated along with albumin and high sensitivity C-reactive protein (hs-CRP) in 30 patients with advanced CKD stages 4 and 5. They were divided into two groups undergoing conservative treatment (CT) (n=15) or hemodialysis (HD) (n=15). An additional group of patients with nephrotic syndrome [CKD stage 2] was also studied to assess the alterations of plasma free amino acids with the early stage of CKD. Another 30 age- and sex-matched healthy children served as controls. A significant increase in plasma concentration of amino acid glutamine was observed in children with advanced CKD stages 4 and 5 when compared with controls (P=0.02).Plasma glutamine level was significantly higher in ESRD children on HD than in children with nephrotic syndrome (P=0.02). We did not find a significant difference between HD children and CT children as regard to glutamine level. Notable differences were in the plasma homocysteine level detected in the CKD groups patients, which was greater than that in controls (P=0.0001). Plasma homocysteine level was significantly higher in children on HD than in children with nephrotic syndrome (P=0.01). A significant differences was observed in hs-CRP levels between the CKD groups and the controls (P=0.04). Albumin levels were lower in CKD groups than in controls (p=0.01). Glutamine showed significant positive correlations with blood urea level (r=0.84, P=0.002) and blood ammonia level (r=0.72, P=0.0001). On multiple linear regression, urea was the only variable independently associated with an elevated plasma glutamine level (Beta=0.77, P=0.02). This study indicates that the advanced stages of CKD are associated with increased plasma concentrations of glutamine and homocysteine. Glutamine retained in the plasma of children with CRF, possibly producing higher levels of the waste products (urea and NH3). Dialysis alone is insufficient to redress completely the abnormalities in AA metabolism in ESRD children. Careful consideration of dialysis and dietary measures are necessary.

Counteraction of urea-induced protein denaturation by trimethylamine N-oxide: a chemical chaperone at atomic resolution.

PubMed

Bennion, Brian J; Daggett, Valerie

2004-04-27

Proteins are very sensitive to their solvent environments. Urea is a common chemical denaturant of proteins, yet some animals contain high concentrations of urea. These animals have evolved an interesting mechanism to counteract the effects of urea by using trimethylamine N-oxide (TMAO). The molecular basis for the ability of TMAO to act as a chemical chaperone remains unknown. Here, we describe molecular dynamics simulations of a small globular protein, chymotrypsin inhibitor 2, in 8 M urea and 4 M TMAO/8 M urea solutions, in addition to other control simulations, to investigate this effect at the atomic level. In 8 M urea, the protein unfolds, and urea acts in both a direct and indirect manner to achieve this effect. In contrast, introduction of 4 M TMAO counteracts the effect of urea and the protein remains well structured. TMAO makes few direct interactions with the protein. Instead, it prevents unfolding of the protein by structuring the solvent. In particular, TMAO orders the solvent and discourages it from competing with intraprotein H bonds and breaking up the hydrophobic core of the protein.

[Degradation of urea and ethyl carbamate in Chinese Rice wine by recombinant acid urease].

PubMed

Zhou, Jianli; Kang, Zhen; Liu, Qingtao; Du, Guocheng; Chen, Jian

2016-01-01

Ethyl carbamate (EC) as a potential carcinogen commonly exists in traditional fermented foods. It is important eliminate urea that is the precursors of EC in many fermented foods, including Chinese Rice wine. On the basis of achieving high-level overexpression of food-grade ethanol-resistant acid urease, we studied the hydrolysis of urea and EC with the recombinant acid urease. Recombinant acid urease showed degraded urea in both the simulated system with ethanol and Chinese Rice wine (60 mg/L of urea was completely degraded within 25 h), indicating that the recombinant enzyme is suitable for the elimination of urea in Chinese Rice wine. Although recombinant acid urease also has degradation catalytic activity on EC, no obvious degradation of EC was observed. Further investigation results showed that the Km value for urea and EC of the recombinant acid urease was 0.7147 mmol/L and 41.32 mmol/L, respectively. The results provided theoretical foundation for realizing simultaneous degradation of urea and EC.

Antitumour evaluation of di-(2-ethylhexyl) phthalate (DEHP) isolated from Calotropis gigantea L. flower.

PubMed

Habib, Muhammad Rowshanul; Karim, Muhammad Rezaul

2012-12-01

The objective of the study is to explore the anticancer activity of di-(2-ethylhexyl) phthalate (DEHP) isolated from Calotropis gigantea flower against Ehrlich ascites carcinoma cells (EAC) in Swiss albino mice. The activity of DEHP was evaluated at doses of 10, 20 and 40 mg kg-1 body mass applied intraperitoneally. DEHP showed a significant decrease in viable cell count (p < 0.05), mass gain (due to tumour burden) and elevated the life span of EAC cell bearing mice. Altered hematological profiles such as RBC, hemoglobin, WBC and differential count were reverted to normal levels in DEHP-treated mice. DEHP also brought back altered biochemical parameters (glucose, cholesterol, triglycerides, blood urea, SALP and SGOT) to normal level. Results of this study indicate that DEHP show potent dose dependent antitumour activity against EAC in vivo.

Metabolic organization of freshwater, euryhaline, and marine elasmobranchs: implications for the evolution of energy metabolism in sharks and rays.

PubMed

Speers-Roesch, B; Ip, Y K; Ballantyne, J S

2006-07-01

To test the hypothesis that the preference for ketone bodies rather than lipids as oxidative fuel in elasmobranchs evolved in response to the appearance of urea-based osmoregulation, we measured total non-esterified fatty acids (NEFA) in plasma as well as maximal activities of enzymes of intermediary metabolism in tissues from marine and freshwater elasmobranchs, including: the river stingray Potamotrygon motoro (<1 mmol l(-1) plasma urea); the marine stingray Taeniura lymma, and the marine shark Chiloscyllium punctatum (>300 mmol l(-1) plasma urea); and the euryhaline freshwater stingray Himantura signifer, which possesses intermediate levels of urea. H. signifer also were acclimated to half-strength seawater (15 per thousand) for 2 weeks to ascertain the metabolic effects of the higher urea level that results from salinity acclimation. Our results do not support the urea hypothesis. Enzyme activities and plasma NEFA in salinity-challenged H. signifer were largely unchanged from the freshwater controls, and the freshwater elasmobranchs did not show an enhanced capacity for extrahepatic lipid oxidation relative to the marine species. Importantly, and contrary to previous studies, extrahepatic lipid oxidation does occur in elasmobranchs, based on high carnitine palmitoyl transferase (CPT) activities in kidney and rectal gland. Heart CPT in the stingrays was detectable but low, indicating some capacity for lipid oxidation. CPT was undetectable in red muscle, and almost undetectable in heart, from C. punctatum as well as in white muscle from T. lymma. We propose a revised model of tissue-specific lipid oxidation in elasmobranchs, with high levels in liver, kidney and rectal gland, low or undetectable levels in heart, and none in red or white muscle. Plasma NEFA levels were low in all species, as previously noted in elasmobranchs. D-beta-hydroxybutyrate dehydrogenase (d-beta-HBDH) was high in most tissues confirming the importance of ketone bodies in elasmobranchs. However, very low d-beta-HBDH in kidney from T. lymma indicates that interspecific variability in ketone body utilization occurs. A negative relationship was observed across species between liver glutamate dehydrogenase activity and tissue or plasma urea levels, suggesting that glutamate is preferentially deaminated in freshwater elasmobranchs because it does not need to be shunted to urea production as in marine elasmobranchs.

Combination of Vildagliptin and Pioglitazone in Experimental Type 2 Diabetes in Male Rats.

PubMed

Refaat, Rowaida; Sakr, Ahmed; Salama, Mona; El Sarha, Ashgan

2016-09-01

Preclinical Research The majority of studies on vildagliptin and pioglitazone have focused on their combination in glycemic control. The aim of the present study was to investigate their effects in combination on (i) hyperglycemia-induced oxidative stress and inflammation and (ii) on organs involved in the pathophysiology of diabetes, pancreas, kidney and liver. Type 2 diabetes was induced using low-dose streptozotocin in male Wistar rats. Diabetic rats were treated for 4 weeks, with vildagliptin (10 mg/kg/day), pioglitazone (10 mg/kg/day) and their combination. Diabetic rats showed elevated fasting serum glucose, fasting serum insulin, serum transaminases together with a deleterious lipid profile and elevated serum creatinine and urea concentrations. Serum levels of the inflammatory markers tumor necrosis factor-α (TNF-α) and nitrite/nitrate were also elevated compared to normal rats. Oxidative stress was manifested by lowered hepatic reduced glutathione (GSH) and increased malondialdehyde (MDA) levels. Pancreatic sections from diabetic rats showed degenerated islets with poorly maintained architecture that was prevented by drug treatment. Pioglitazone was generally more effective than vildagliptin in the studied parameters except for the lipid profile where the effect of both drugs was comparable and for the liver enzymes and renal parameters where vildagliptin was more effective. The combination of vildagliptin and pioglitazone produced superior effects than either drug alone. Drug Dev Res 77 : 251-257, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Modeling of flux, binding and substitution of urea molecules in the urea transporter dvUT.

PubMed

Zhang, Hai-Tian; Wang, Zhe; Yu, Tao; Sang, Jian-Ping; Zou, Xian-Wu; Zou, Xiaoqin

2017-09-01

Urea transporters (UTs) are transmembrane proteins that transport urea molecules across cell membranes and play a crucial role in urea excretion and water balance. Modeling the functional characteristics of UTs helps us understand how their structures accomplish the functions at the atomic level, and facilitates future therapeutic design targeting the UTs. This study was based on the crystal structure of Desulfovibrio vulgaris urea transporter (dvUT). To model the binding behavior of urea molecules in dvUT, we constructed a cooperative binding model. To model the substitution of urea by the urea analogue N,N'-dimethylurea (DMU) in dvUT, we calculated the occupation probability of DMU along the urea pore and the ratio of the occupation probabilities of DMU at the external (S ext ) and internal (S int ) binding sites, and we established the mutual substitution rule for binding and substitution of urea and DMU. Based on these calculations and modelings, together with the use of the Monte Carlo (MC) method, we further modeled the urea flux in dvUT, equilibrium urea binding to dvUT, and the substitution of urea by DMU in the dvUT. Our modeling results are in good agreement with the existing experimental functional data. Furthermore, the modelings have discovered the microscopic process and mechanisms of those functional characteristics. The methods and the results would help our future understanding of the underlying mechanisms of the diseases associated with impaired UT functions and rational drug design for the treatment of these diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

Influence of salt intake, ANG II synthesis and SFO lesion on thirst and blood pressure during sodium depletion. Subfornical organ.

PubMed

Starbuck, E M; Fitts, D A

1998-12-01

Water intake was elevated in sodium-depleted rats during a daytime salt appetite test, but other rats drank a similar amount of water when saline was not available for drinking during the test. This water intake stimulated by sodium depletion was blocked by an inhibition of angiotensin (ANG) II synthesis with a high dose of captopril (100 mg/kg, sc). Captopril did not reduce water intake by causing hypotensive shock or uremia, because water and saline intakes were increased rather than decreased after a low dose of captopril (5 mg/kg) that also reduced blood pressure and elevated blood urea nitrogen. The water intake, but not salt appetite, induced by sodium depletion was greatly reduced by a lesion of the subfornical organ (SFO) in one-bottle tests, and this was not clearly related to any effects of the lesion on blood pressure. A physiological role for ANG II in water intake induced by sodium depletion has recently been disputed, but the simplest explanation for the data remains that elevated levels of circulating ANG II bind to receptors in the SFO to generate daytime water drinking during sodium depletion.

Na(+) regulation by combined nitrogen in Azolla pinnata-Anabaena azollae symbiotic association during salt toxicity.

PubMed

Singh, Satya S; Singh, Santosh K; Mishra, Arun K

2008-01-01

To study the regulation of Na(+) ion by combined-N sources in Azolla pinnata-Anabaena azollae, Na(+) influx, intracellular Na(+) and Na(+) efflux were investigated in the presence of different N-sources (N(2), NH(4)(+), NO(3)(-) and urea) and various NaCl concentrations. Sodium influx by Azolla pinnata fronds was minimum in the presence of NO(3)(-). Almost identical levels of intracellular sodium, although less than N(2) and NH(4)(+) incubated fronds were observed in the presence of NO(3)(-) and urea. Efflux of sodium was minimum in urea and NO(3)(-) grown fronds. A low residual sodium was observed in the fronds incubated in NO(3)(-) and urea supplemented media. Results suggest that nitrate and urea curtailed the entry of sodium, reduced salt toxicity maximally by maintaining the minimum level of sodium and also conserved energy due to slow influx and efflux of Na(+) within the fronds during salt shock and the process of adaptation.

Selective removal of organics for water reclamation

NASA Technical Reports Server (NTRS)

Murphy, Oliver J.; Hitchens, G. Duncan

1989-01-01

Electrolysis has been investigated as a means of purifying waste water. The feasibility of the direct electrochemical oxidation of urea has been demonstrated. Urea levels were reduced from 1200 ppm to 1 ppm forming the basis for a new approach to urine purification where the only consumable is electrical energy. Preliminary estimates of the energy requirements are 270 W/hr per liter of urine. Urea oxidation rates of around 350 mg urea/hr/m2 were observed. It is anticipated that a 1 m2 geometric area of electrode could treat urine for a crew of several persons. The low levels of organic contaminants resulting from this treatment indicate that the approach may have an impact as a post treatment process. Experiments are planned to investigate this later possibility.

Urea recycling contributes to nitrogen retention in calves fed milk replacer and low-protein solid feed.

PubMed

Berends, Harma; van den Borne, Joost J G C; Røjen, Betina A; van Baal, Jürgen; Gerrits, Walter J J

2014-07-01

Urea recycling, with urea originating from catabolism of amino acids and hepatic detoxification of ammonia, is particularly relevant for ruminant animals, in which microbial protein contributes substantially to the metabolizable protein supply. However, the quantitative contribution of urea recycling to protein anabolism in calves during the transition from preruminants (milk-fed calves) to ruminants [solid feed (SF)-fed calves] is unknown. The aim of this study was to quantify urea recycling in milk-fed calves when provided with low-protein SF. Forty-eight calves [164 ± 1.6 kg body weight (BW)] were assigned to 1 of 4 SF levels [0, 9, 18, and 27 g of dry matter (DM) SF · kg BW(-0.75) · d⁻¹] provided in addition to an identical amount of milk replacer. Urea recycling was quantified after a 24-h intravenous infusion of [¹⁵N₂]urea by analyzing urea isotopomers in 68-h fecal and urinary collections. Real-time qPCR was used to measure gene expression levels of bovine urea transporter B (bUTB) and aquaglyceroporin-3 and aquaglyceroporin-7 in rumen wall tissues. For every incremental gram of DM SF intake (g DM · kg(0.75)), nitrogen intake increased by 0.70 g, and nitrogen retention increased by 0.55 g (P < 0.01). Of this increase in nitrogen retention, 19% could be directly explained by urea recycling. Additionally, part of the observed increase in nitrogen retention could be explained by the extra protein provided by the SF and likely by a greater efficiency of postabsorptive use of nitrogen for gain. Ruminal bUTB abundance increased (P < 0.01) with SF provision. Aquaglyceroporin-3 expression increased (P < 0.01) with SF intake, but aquaglyceroporin-7 expression did not. We conclude that in addition to the increase in digested nitrogen, urea recycling contributes to the observed increase in nitrogen retention with increasing SF intake in milk-fed calves. Furthermore, ruminal bUTB and aquaglyceroporin-3 expression are upregulated with SF intake, which might be associated with urea recycling. © 2014 American Society for Nutrition.

Taste acuity, plasma zinc levels, and weight loss during radiotherapy: a study of relationships

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bolze, M.S.; Fosmire, G.J.; Stryker, J.A.

1982-07-01

Thirty-five patients who were to undergo radiotherapy and 13 normal subjects were evaluated with taste questionnaires, taste acuity tests, and plasma zinc analyses. The studies were repeated on the patients in the fifth week of radiotherapy. The mean taste thresholds for NaCl (salt), sucrose (sweet), HCl (sour), and urea (bitter) were elevated and the plasma zinc levels were lower (77.2 +/- 11.8 vs. 94.6 +/- 30.1 g/100 ml, p = 0.055) for the patients than for the controls. However, there was not a significant correlation between the taste thresholds and plasma zinc levels at any time. The mean weight lossmore » experienced by the 14 patients who reported subjective taste alteration in the fifth week was 3.1 kg versus 0.1 kg (p = 0.005) for those who did not report taste alteration. The data suggest that alterations in taste acuity, but not plasma zinc levels, are associated with weight loss during radiotherapy.« less

Taste acuity, plasma zinc levels, and weight loss during radiotherapy: a study of relationships

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bolze, M.S.; Fosmire, G.J.; Stryker, J.A.

1982-07-01

Thirty-five patients who were to undergo radiotherapy and 13 normal subjects were evaluated with taste questionnaires, taste acuity tests, and plasma zinc analyses. The studies were repeated on the patients in the fifth week of radiotherapy. The mean taste thresholds for NaCl (salt), sucrose (sweet), HCl (sour), and urea (bitter) were elevated and the plasma zinc levels were lower (77.2 +/- 11.8 vs. 94.6 +/- 30.1 g/100 ml, p . 0.055) for the patients than for the controls. However, there was not a significant correlation between the taste thresholds and plasma zinc levels at any time. The mean weight lossmore » experienced by the 14 patients who reported subjective taste alteration in the fifth week was 3.1 kg versus 0.1 kg (p . 0.005) for those who did not report taste alteration. The data suggest that alterations in taste acuity, but not plasma zinc levels, are associated with weight loss during radiotherapy.« less

The emerging physiological roles of the SLC14A family of urea transporters

PubMed Central

Stewart, Gavin

2011-01-01

In mammals, urea is the main nitrogenous breakdown product of protein catabolism and is produced in the liver. In certain tissues, the movement of urea across cell membranes is specifically mediated by a group of proteins known as the SLC14A family of facilitative urea transporters. These proteins are derived from two distinct genes, UT-A (SLC14A2) and UT-B (SLC14A1). Facilitative urea transporters play an important role in two major physiological processes – urinary concentration and urea nitrogen salvaging. Although UT-A and UT-B transporters both have a similar basic structure and mediate the transport of urea in a facilitative manner, there are a number of significant differences between them. UT-A transporters are mainly found in the kidney, are highly specific for urea, have relatively lower transport rates and are highly regulated at both gene expression and cellular localization levels. In contrast, UT-B transporters are more widespread in their tissue location, transport both urea and water, have a relatively high transport rate, are inhibited by mercurial compounds and currently appear to be less acutely regulated. This review details the fundamental research that has so far been performed to investigate the function and physiological significance of these two types of urea transporters. PMID:21449978

Urea cycle disorder misdiagnosed as multiple sclerosis: a case report and review of the literature.

PubMed

Algahtani, Hussein; Alameer, Seham; Marzouk, Yousef; Shirah, Bader

2018-04-01

Urea cycle disorders are a group of inborn errors of metabolism caused by dysfunction of any of the six enzymes or two transport proteins involved in urea biosynthesis. In this paper, we report a patient who presented with neurological dysfunction and coma in the immediate postpartum period. She was misdiagnosed for many years as a case of multiple sclerosis. The importance of reporting this case is to illustrate that the wrong diagnosis of patients as being affected with multiple sclerosis for many years due to magnetic resonance imaging abnormalities rather than the classic relapsing-remitting nature of the disease may lead to catastrophic consequences. The patient was treated with intravenous steroids several times, which is contraindicated in patients with urea cycle disorders as it may precipitate acute hyperammonemic attacks. In addition, the management of urea cycle disorder could have started earlier and avoided multiple admissions to the intensive care unit. We believe that the presence of symmetric hyperintense insular cortical changes are seen in multiple hyperammonemic processes, and in the context of the clinical presentation and high ammonia levels can be suggestive of a urea cycle disorder. For any patient presenting with atypical clinical features, images should be reviewed and discussed in detail with an experienced neuroradiologist. In addition, the ammonia levels should be checked if a urea cycle disorder is suspected.

Plasma pentosidine levels measured by a newly developed method using ELISA in patients with chronic renal failure.

PubMed

Sanaka, Tsutomu; Funaki, Takenori; Tanaka, Toshihisa; Hoshi, Sayako; Niwayama, Jyun; Taitoh, Takashi; Nishimura, Hideki; Higuchi, Chieko

2002-05-01

The plasma pentosidine levels in patients with renal disease were measured by a simple method which was established for plasma and urinary pentosidine determinations. The method, which can be completed within a few hours, involves pretreating plasma with proteolytic enzyme (pronase) and measuring the concentration of pentosidine in the sample by ELISA using antipentosidine antibodies. The prepared antibodies showed no cross-reaction with the raw materials for pentosidine synthesis or with compounds having similar structures. SDS-PAGE indicated that the antibodies had a high purity. The reaction of the antibodies and keyhole limpet hemocyanin-pentosidine in the competitive ELISA system was inhibited by free pentosidine. Excellent standard curves for pentosidine determination were obtained. In actual measurements of clinical samples from patients, a good correlation (r = 0.9356) was obtained between the values measured by ELISA and HPLC. The plasma pentosidine level in patients with renal disease correlated significantly with plasma creatinine, urea nitrogen, beta2-microglobulin, and creatinine clearance, indicating its usefulness in evaluating the severity of renal disease. A significant elevation in plasma pentosidine levels was observed in mild renal dysfunction, whereas no significant increases in creatinine and urea nitrogen levels were detected, suggesting that the plasma pentosidine level is useful in the early diagnosis of beginning renal failure. In patients with chronic renal failure, no difference in plasma pentosidine levels was observed between diabetic nephropathy and chronic glomerulonephritis, while a significant correlation was observed with phosphatidylcholine hydroperoxide, suggesting the possibility that the plasma pentosidine level reflects injury due to oxidation. From these results, the quantitative measurement method developed by us is judged to be a superior innovation for measuring pentosidine in body fluids. The plasma pentosidine level may be useful for the early diagnosis of mild renal failure and to estimate the degree of the severity of renal diseases. Copyright 2002 S. Karger AG, Basel

Effect of urea-supplemented diets on the ruminal bacterial and archaeal community composition of finishing bulls.

PubMed

Zhou, Zhenming; Meng, Qingxiang; Li, Shengli; Jiang, Lan; Wu, Hao

2017-08-01

In this study, we evaluated the effects of urea-supplemented diets on the ruminal bacterial and archaeal communities of finishing bulls using sequencing technology. Eighteen bulls were fed a total mixed ration based on maize silage and concentrate (40:60) and randomly allocated to one of three experimental diets: a basal diet with no urea (UC, 0%), a basal diet supplemented with low urea levels (UL, 0.8% dry matter (DM) basis), and a basal diet supplemented with high urea levels (UH, 2% DM basis). All treatments were iso-nitrogenous (14% crude protein, DM basis) and iso-metabolic energetic (ME = 11.3 MJ/kg, DM basis). After a 12-week feeding trial, DNA was isolated from ruminal samples and used for 16S rRNA gene amplicon sequencing. For bacteria, the most abundant phyla were Firmicutes (44.47%) and Bacteroidetes (41.83%), and the dominant genera were Prevotella (13.17%), Succiniclasticum (4.24%), Butyrivibrio (2.36%), and Ruminococcus (1.93%). Urea supplementation had no effect on most phyla (P > 0.05), while there was a decreasing tendency in phylum TM7 with increasing urea levels (P = 0.0914). Compared to UC, UH had lower abundance of genera Butyrivibrio and Coprococcus (P = 0.0092 and P = 0.0222, respectively). For archaea, the most abundant phylum was Euryarchaeota (99.81% of the sequence reads), and the most abundant genus was Methanobrevibacter (90.87% of the sequence reads). UH increased the abundance of genus Methanobrevibacter and Methanobacterium (P = 0.0299 and P = 0.0007, respectively) and decreased the abundance of vadinCA11 (P = 0.0151). These findings suggest that urea-supplemented diets were associated with a shift in archaeal biodiversity and changes in the bacterial community in the rumen.

How a protein can remain stable in a solvent with high content of urea: insights from molecular dynamics simulation of Candida antarctica lipase B in urea : choline chloride deep eutectic solvent.

PubMed

Monhemi, Hassan; Housaindokht, Mohammad Reza; Moosavi-Movahedi, Ali Akbar; Bozorgmehr, Mohammad Reza

2014-07-28

Deep eutectic solvents (DESs) are utilized as green and inexpensive alternatives to classical ionic liquids. It has been known that some of DESs can be used as solvent in the enzymatic reactions to obtain very green chemical processes. DESs are quite poorly understood at the molecular level. Moreover, we do not know much about the enzyme microstructure in such systems. For example, how some hydrolase can remain active and stable in a deep eutectic solvent including 9 M of urea? In this study, the molecular dynamics of DESs as a liquid was simulated at the molecular level. Urea : choline chloride as a well-known eutectic mixture was chosen as a model DES. The behavior of the lipase as a biocatalyst was studied in this system. For comparison, the enzyme structure was also simulated in 8M urea. The thermal stability of the enzyme was also evaluated in DESs, water, and 8M urea. The enzyme showed very good conformational stability in the urea : choline chloride mixture with about 66% urea (9 M) even at high temperatures. The results are in good agreement with recent experimental observations. In contrast, complete enzyme denaturation occurred in 8M urea with only 12% urea in water. It was found that urea molecules denature the enzyme by interrupting the intra-chain hydrogen bonds in a "direct denaturation mechanism". However, in a urea : choline chloride deep eutectic solvent, as a result of hydrogen bonding with choline and chloride ions, urea molecules have a low diffusion coefficient and cannot reach the protein domains. Interestingly, urea, choline, and chloride ions form hydrogen bonds with the surface residues of the enzyme which, instead of lipase denaturation, leads to greater enzyme stability. To the best of our knowledge, this is the first study in which the microstructural properties of a macromolecule are examined in a deep eutectic solvent.

Deceiving proteins! A case of lymphoma and high creatinine.

PubMed

Metraiah, El Hakem Abdelkarim; Regan, Helen; Louw, Johanna; Kidder, Dana

2017-01-23

Estimation of kidney function by measuring serum creatinine is one the commonest laboratory tests conducted in clinical practice. Enzymatic methods are often used to measure serum creatinine. Clinicians should be aware of the limitations of these methods, such as test interference with paraproteins.We present a case of falsely elevated serum creatinine in a patient referred for renal biopsy. The combination of fluctuating creatinine and normal blood urea level was unusual. Serum protein electrophoresis revealed the presence of an IgM paraprotein. Further investigations confirmed an underlying diagnosis of lymphoplasmacytoid lymphoma. This case highlights how IgM paraprotein can interfere with creatinine estimation by enzymatic assay and the utility of alternative methods of estimating serum creatinine. 2017 BMJ Publishing Group Ltd.

[A patient with high creatinine levels but no renal failure: reversed autodialysis in a patient with a ruptured bladder].

PubMed

Raeymaeckers, Steven; Tosi, Maurizio; Van Bael, Kobe; Brussaard, Carola; De Mey, Johan

2016-01-01

In case of a ruptured bladder with urine leakage into the peritoneal cavity 'reversed autodialysis' can occur, in which urea and creatinine diffuse back into the bloodstream via the peritoneum. This causes clinical signs of pseudorenal failure, with raised concentrations of creatinine and urea. The urea/creatinine ratio does not change. A 34-year-old female patient experienced increasing abdominal pain 3 days after laparoscopic myomectomy. Acute renal failure was suspected because of increased serum concentrations of creatinine and urea, but no cause could be found. There was a build-up of fluid in the abdominal cavity, which proved to be urine originating from an iatrogenic rupture of the bladder. Serum levels normalised following repair of the rupture. If serum creatinine levels rise rapidly following abdominal surgery or blunt abdominal trauma the bladder should be examined for possible perforation, particularly if the abdominal dimension increases. A ruptured bladder leading to pseudorenal failure is an indication for rapid surgical intervention.

Vitamin E mitigates cisplatin-induced nephrotoxicity due to reversal of oxidative/nitrosative stress, suppression of inflammation and reduction of total renal platinum accumulation.

PubMed

Darwish, Mostafa A; Abo-Youssef, Amira M; Khalaf, Marwa M; Abo-Saif, Ali A; Saleh, Ibrahim G; Abdelghany, Tamer M

2017-01-01

Cisplatin (CP) is one of the most effective chemotherapeutic agents. Unfortunately, CP-induced nephrotoxicity hampered its use. This study aims to investigate the effect of vitamin E (Vit E) on CP-induced nephrotoxicity. Male white albino rats were divided to four group's six rats each and received either, 1% tween 80 in normal saline or Vit E (75 mg/kg) per day for 14 consecutive days or a single injection of CP (6 mg/kg) alone or CP (6 mg/kg) together with Vit E (75 mg/kg per day for 14 consecutive days). Five days after the CP injection, rats were euthanized; blood samples were collected; kidneys were dissected; and biochemical, immunohistochemical, and histological examinations were performed. Our results revealed that CP treatment significantly increased serum levels of creatinine and urea. Moreover, reduced glutathione (GSH) content as well as superoxide dismutase (SOD) and catalase (CAT) activities were significantly reduced with concurrent increase in kidney malondialdehyde (MDA) content following CP treatment. Vit E successfully lowered serum levels of urea and creatinine, enhanced creatinine clearance and diuresis, and normalized relative kidney/body weight. Furthermore, Vit E successfully normalized renal MDA and nitrite concentrations, elevated GSH level, and restored CAT and SOD activities in renal tissues. Histopathological examination of rat kidney revealed that Vit E significantly mitigated CP-induced renal damage. Importantly, administration of Vit E reduced kidney total platinum concentration indicating a role of platinum renal accumulation on the ability of Vit E to protect against CP nephrotoxicity. © 2016 Wiley Periodicals, Inc.

Effects of chlorimuron-ethyl application with or without urea fertilization on soil ammonia-oxidizing bacteria and archaea.

PubMed

Tan, Huanbo; Xu, Mingkai; Li, Xinyu; Zhang, Huiwen; Zhang, Chenggang

2013-09-15

Chlorimuron-ethyl (CE) has been widely used in modern agriculture, but little is known regarding the influence of CE on ammonia-oxidizing bacteria (AOB) and archaea (AOA) populations in soils. In this study, microcosm incubation of aquic brown soil was conducted for 60 d. Associated changes in the population sizes of AOB and AOA in response to CE application with or without urea fertilization were examined via quantitative real-time PCR (qPCR) assays of the ammonia monooxygenase gene (amoA). The half-life of CE ranged from 11.80 d to 14.54 d in the tested soil. Compared to the untreated control, the application of CE alone had no strong effects on soil pH, and urea fertilization temporarily increased soil pH in the first 7 days. The abundance of the AOA amoA gene was greater than the abundance of the AOB amoA gene in all treatments, but both were significantly suppressed by CE application in a dose-dependent manner. Urea fertilization generally increased AOB and AOA amoA gene abundances, except that the AOA amoA gene level was slightly reduced at the early stage of the incubation period. AOB and AOA preferred different N levels for growth, with AOB only growing significantly at high NH4(+) levels and AOA growing substantially at low NH₄(+) levels. The stimulation effects of urea fertilization on AOA and AOB amoA gene abundances were strongly suppressed by the CE application. This study indicated that the CE application substantially suppressed soil nitrification via inhibiting the AOB and AOA population regardless of urea fertilization, which resulted in significant changes in the soil NH₄(+)-N and NO₃(-)-N levels. Furthermore, AOB and AOA inhabiting separate ecological niches with different NH₄(+) levels played various roles in N cycling. Copyright © 2013 Elsevier B.V. All rights reserved.

Cells for bioartificial liver devices: the human hepatoma-derived cell line C3A produces urea but does not detoxify ammonia.

PubMed

Mavri-Damelin, Demetra; Damelin, Leonard H; Eaton, Simon; Rees, Myrddin; Selden, Clare; Hodgson, Humphrey J F

2008-02-15

Extrahepatic bioartificial liver devices should provide an intact urea cycle to detoxify ammonia. The C3A cell line, a subclone of the hepatoma-derived HepG2 cell line, is currently used in this context as it produces urea, and this has been assumed to be reflective of ammonia detoxification via a functional urea cycle. However, based on our previous findings of perturbed urea-cycle function in the non-urea producing HepG2 cell line, we hypothesized that the urea produced by C3A cells was via a urea cycle-independent mechanism, namely, due to arginase II activity, and therefore would not detoxify ammonia. Urea was quantified using (15)N-ammonium chloride metabolic labelling with gas chromatography-mass spectrometry. Gene expression was determined by real-time reverse transcriptase-PCR, protein expression by western blotting, and functional activities with radiolabelling enzyme assays. Arginase inhibition studies used N(omega)-hydroxy-nor-L-arginine. Urea was detected in C3A conditioned medium; however, (15)N-ammonium chloride-labelling indicated that (15)N-ammonia was not incorporated into (15)N-labelled urea. Further, gene expression of two urea cycle genes, ornithine transcarbamylase and arginase I, were completely absent. In contrast, arginase II mRNA and protein was expressed at high levels in C3A cells and was inhibited by N(omega)-hydroxy-nor-L-arginine, which prevented urea production, thereby indicating a urea cycle-independent pathway. The urea cycle is non-functional in C3A cells, and their urea production is solely due to the presence of arginase II, which therefore cannot provide ammonia detoxification in a bioartificial liver system. This emphasizes the continued requirement for developing a component capable of a full repertoire of liver function. (c) 2007 Wiley Periodicals, Inc.

Efficiencies of Low-Level Laser Therapy (LLLT) and Gabapentin in the Management of Peripheral Neuropathy: Diabetic Neuropathy.

PubMed

Abdel-Wahhab, Khaled G; Daoud, Eitedal M; El Gendy, Aliaa; Mourad, Hagar H; Mannaa, Fathia A; Saber, Maha M

2018-03-12

Diabetic neuropathy (DN) is the highly occurred complication of diabetes mellitus; it has been defined as an event of peripheral nerve dysfunction characterized by pain, allodynia, hyperalgesia, and paraesthesia. The current study was conducted to evaluate the efficacy of low-level laser therapy (LLLT) in the management of neuropathy in diabetic rats. The used animals were divided into the following groups: negative control, streptozotocin-induced diabetic rats, and diabetic rats with peripheral neuropathy (DNP) and DNP treated with gabapentin or with LLLT. Behavioral tests were carried out through hotplate test for the determination of pain sensations and the Morris water maze test for spatial reference memory evaluation. Blood samples were collected at the end of treatment for biochemical determinations. In the current study, the latency of hind-paw lick decreased significantly when DNP are treated with gabapentin or LLLT. The Morris water maze test showed that LLLT treatment improved memory that deteriorated in DNP more than gabapentin do. The results of the biochemical study revealed that LLLT could not affect the level of beta-endorphin that decreased in DNP but significantly decreased S100B that rose in DNP. PGE2 and cytokines IL-1β, IL-10, and TNF-α showed significant increase in DNP compared with control group. The gabapentin administration or LLLT application significantly reversed the levels of the mentioned markers towards the normal values of the controls. Levels of serum MDA and nitric oxide increased significantly in the DNP but rGSH showed significant decrease. These markers were improved significantly when the DNP were treated with gabapentin or LLLT. The treatment with gabapentin or LLLT significantly decreased the raised level in total cholesterol in DNP but could not decrease the elevated level of triglycerides, while LDL cholesterol decreased significantly in DNP treated with gabapentin but not affected by LLLT. Values of serum alanine aminotransferase (ALAT), aspartate aminotransferase (ASAT), urea, and creatinine increased significantly in the DPN and diabetic rats without peripheral neuropathy (PN) compared with control group. The treatment of DNP with gabapentin induced significant increases in ALAT and ASAT activities but LLLT treatment induced significant decreases in ALAT and ASAT activities as compared with DNP group. Neither gabapentin nor LLLT could improve the elevated levels of serum urea and creatinine in the DNP. It could be concluded that LLLT is more safe and effective than gabapentin in the management of neuropathy in diabetic rats.

Comparative effects of vitamin E and kolaviron (a biflavonoid from Garcinia kola) on carbon tetrachloride-induced renal oxidative damage in mice.

PubMed

Adaramoye, O A

2009-08-15

It became evident in this study that carbon tetrachloride (CCl4), can induce renal oxidative damage. The hepatoprotective effects of vitamin E (Vit. E) and kolaviron (KV), a biflavonoid complex from the seeds of Garcinia kola are well documented. The present study was designed to investigate and compare the renal protective effects of Vit. E and KV in mice given CCl4 (1.2 g kg(-1)) intra-peritoneally thrice a week for two weeks. CCl4 caused a marked increase in serum and renal lipid peroxidation (LPO) by 106 and 225%, respectively. Treatment with KV at 100 and 200 mg kg(-1) and Vit. E at 100 mg kg(-1) significantly (p < 0.05) decreased the CCl4-mediated increase in LPO. Furthermore, CCl4-intoxication decreased the levels of renal reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) by 44, 56 and 43%, respectively. Treatment with KV and Vit. E significantly (p < 0.05) ameliorated the GSH and SOD levels. Specifically, KV at 100 and 200 mg kg(-1) increased GSH by 32 and 27% and SOD levels by 50 and 53%, respectively. Likewise, treatment with Vit. E increased GSH and SOD levels by 31 and 53%, respectively. Effects on markers of renal functions showed that CCl4-intoxication significantly (p < 0.05) elevated serum urea and creatinine by 287 and 186%, respectively. While treatment with Vit. E decreased serum urea and creatinine by 60 and 55%, respectively, KV produced insignificant (p > 0.05) effect on these parameters. This study found KV unable to protect against CCl4-induced renal damage but confirmed the potency of Vit. E to enhance recovery from renal oxidative damage.

Passive regeneration of glutathione: glutathione reductase regulation in the freeze-tolerant North American wood frog, Rana sylvatica.

PubMed

Dawson, Neal J; Storey, Kenneth B

2017-09-01

Wood frogs inhabit a broad range across North America, extending from the southern tip of the Appalachian Mountains to the northern boreal forest. Remarkably, they can survive the winter in a frozen state, where as much as 70% of their body water is converted into ice. Whilst in the frozen state, their hearts cease to pump blood, causing their cells to experience ischemia, which can dramatically increase the production of reactive oxygen species within the cell. To overcome this, wood frogs have elevated levels of glutathione, a primary antioxidant. We examined the regulation of glutathione reductase, the enzyme involved in recycling glutathione, in both the frozen and unfrozen (control) state. Glutathione reductase activity from both the control and frozen state showed a dramatic reduction in substrate specificity ( K m ) for oxidized glutathione (50%) when measured in the presence of glucose (300 mmol l -1 ) and a increase (157%) when measured in the presence of levels of urea (75 mmol l -1 ) encountered in the frozen state. However, when we tested the synergistic effect of urea and glucose simultaneously, we observed a substantial reduction in the K m for oxidized glutathione (43%) to a value similar to that with glucose alone. In fact, we found no observable differences in the kinetic and structural properties of glutathione reductase between the two states. Therefore, a significant increase in the affinity for oxidized glutathione in the presence of endogenous levels of glucose suggests that increased glutathione recycling may occur as a result of passive regulation of glutathione reductase by rising levels of glucose during freezing. © 2017. Published by The Company of Biologists Ltd.

Nitrogen metabolism of the intestine during digestion in a teleost fish, the plainfin midshipman (Porichthys notatus).

PubMed

Bucking, Carol; LeMoine, Christophe M R; Craig, Paul M; Walsh, Patrick J

2013-08-01

Digestion affects nitrogen metabolism in fish, as both exogenous and endogenous proteins and amino acids are catabolized, liberating ammonia in the process. Here we present a model of local detoxification of ammonia by the intestinal tissue of the plainfin midshipman (Porichthys notatus) during digestion, resulting in an increase in urea excretion of gastrointestinal origin. Corroborating evidence indicated whole-animal ammonia and urea excretion increased following feeding, and ammonia levels within the lumen of the midshipman intestine increased to high levels (1.8±0.4 μmol N g(-1)). We propose that this ammonia entered the enterocytes and was detoxified to urea via the ornithine-urea cycle (O-UC) enzymes, as evidenced by a 1.5- to 2.9-fold post-prandial increase in glutamine synthetase activity (0.14±0.05 and 0.28±0.02 μmol min(-1) g(-1) versus 0.41±0.03 μmol min(-1) g(-1)) and an 8.7-fold increase in carbamoyl phosphate synthetase III activity (0.3±1.2 versus 2.6±0.4 nmol min(-1) g(-1)). Furthermore, digestion increased urea production by isolated gastrointestinal tissue 1.7-fold, supporting our hypothesis that intestinal tissue synthesizes urea in response to feeding. We further propose that the intestinal urea may have been excreted into the intestinal lumen via an apical urea transporter as visualized using immunohistochemistry. A portion of the urea was then excreted to the environment along with the feces, resulting in the observed increase in urea excretion, while another portion may have been used by intestinal ureolytic bacteria. Overall, we propose that P. notatus produces urea within the enterocytes via a functional O-UC, which is then excreted into the intestinal lumen. Our model of intestinal nitrogen metabolism does not appear to be universal as we were unab le to activate the O-UC in the intestine of fed rainbow trout. However, literature values suggest that multiple fish species could follow this model.

Noncirrhotic Extrahepatic Portosystemic Shunt Causing Adult-Onset Encephalopathy Treated with Endovascular Closure

PubMed Central

Elnekave, Eldad; Belenky, Eugenia; Van der Veer, Lindsley

2015-01-01

A 54-year-old woman presented with a six-month history of episodic confusion and progressive ataxia. A comprehensive metabolic panel was notable for elevated values of alkaline phosphatase (161 U/L), total bilirubin (1.5 mg/dL), and serum ammonia of 300 umol/L (normal range 9–47). Hepatitis panel, relevant serological tests, tumor markers (CA-19-9, CEA), and urea cycle enzyme studies were unrevealing. Lactulose and rifaximin therapy failed to normalize serum ammonia levels. Imaging revealed a structural vascular abnormality communicating between an enlarged inferior mesenteric vein and the left renal vein, measuring 16 mm in greatest diameter. The diagnosis of congenital extrahepatic portosystemic shunt was made and endovascular shunt closure was performed using a 22 mm Amplatzer II vascular plug. Within a day, serum ammonia levels normalized. Lactulose and rifaximin were discontinued, and confusion and ataxia resolved. PMID:26199783

Exposure to ammonia and acute respiratory effects in a urea fertilizer factory.

PubMed

Rahman, Md Hamidur; Bråtveit, Magne; Moen, Bente E

2007-01-01

Personal exposures to ammonia and acute respiratory effects were determined in workers at a urea fertilizer factory in Bangladesh. Full-shift personal exposure to ammonia was measured using a PAC III direct reading instrument and Drager diffusion tubes. Respiratory symptoms were elicited by a questionnaire study (n = 113), and preshift and postshift lung function (FVC, FEV1, and PEFR) were tested using spirometry (n = 88). Urea plant workers had higher mean exposure to ammonia and prevalence of acute respiratory symptoms than did workers in the ammonia plant. The symptoms with highest prevalence in the urea plant were chest tightness (33%) and cough (28%). FVC and FEV1 decreased significantly across the work shift among urea plant workers. The higher level of exposure to ammonia in the urea plant was associated with an increased prevalence of respiratory symptoms and an acute decline in lung function.

Variables that affect the mechanism of drug release from osmotic pumps coated with acrylate/methacrylate copolymer latexes.

PubMed

Jensen, J L; Appel, L E; Clair, J H; Zentner, G M

1995-05-01

The feasibility of using modified Eudragit acrylic latexes as microporous coatings for osmotic devices was investigated. Potassium chloride tablets were coated with mixtures of Eudragit RS30D and RL30D acrylic latexes that also contained a plasticizer (triethyl citrate or acetyl tributyl citrate) and a pore-forming agent (urea). A 2(5-1) fractional factorial experimental design was employed to determine the effect of five formulation variables (RS30D:RL30D polymer ratio plasticizer type, plasticizer level, urea level, and cure) on the in vitro release rate of KCl in deionized water (di water), lag time, and coat burst strength. The RS30D:RL30D polymer ratio had the greatest effect on the release rate, and both lag time and burst strength were most affected by the urea level. Statistical optimization was performed, and a coat formulation with predicted desirable in vitro performance was prepared and tested. The in vitro release rate (di water), lag time, and coat burst strength agreed well with the prediction. Dissolutions were also performed in phosphate buffered saline (PBS; pH 7.4); several formulations released markedly slower in PBS than in di water. This discrepancy was dependent on the type of plasticizer and the amount of pore former. Only those coat formulations containing acetyl tributyl citrate as the plasticizer and a 100% urea [(g urea/g polymer solids) x 100] level exhibited similar release rates in di water and PBS. The mechanism of release from these devices was primarily osmotic, whereas the release from devices coated with a formulation containing triethyl citrate and 50% urea was not dependent on the osmotic pressure difference. Devices with an osmotic release mechanism behaved similarly in vivo and in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

Utilization of immobilized urease for waste water treatment

NASA Technical Reports Server (NTRS)

Husted, R. R.

1974-01-01

The feasibility of using immobilized urease for urea removal from waste water for space system applications is considered, specifically the elimination of the urea toxicity problem in a 30-day Orbiting Frog Otolith (OFO) flight experiment. Because urease catalyzes the hydrolysis of urea to ammonia and carbon dioxide, control of their concentrations within nontoxic limits was also determined. The results of this study led to the use of free urease in lieu of the immobilized urease for controlling urea concentrations. An ion exchange resin was used which reduced the NH3 level by 94% while reducing the sodium ion concentration only 10%.

Banding of urea increased ammonia volatilization in a dry acidic soil.

PubMed

Rochette, Philippe; Macdonald, J Douglas; Angers, Denis A; Chantigny, Martin H; Gasser, Marc-Olivier; Bertrand, Normand

2009-01-01

Volatilization of ammonia following application of urea contributes to smog formation and degradation of natural ecosystems. The objective of this study was to evaluate the impact of (i) incorporation and banding of urea and (ii) surface broadcast of slow-release urea types on NH(3) volatilization in a dry acidic soil. Volatilization was measured using wind tunnels for 25 d after standard urea (140 kg N ha(-1)) was broadcast, broadcast and incorporated (0-5 cm), or incorporated in shallow bands (3-5 cm) to a conventionally tilled silty loam soil. Urea supplemented with a urease inhibitor or coated with a polymer was also broadcast at the soil surface. Little N diffused out of the polymer-coated granules and ammonia losses were low (4% of applied N). Use of a urease inhibitor also resulted in a low NH(3) loss (5% of applied N) while maintaining soil mineral N at levels similar to plots where untreated urea was broadcast. The rate of hydrolysis of urea broadcast at the soil surface was slowed by the lack of moisture and NH(3) loss (9% applied N) was the lowest of all treatments with standard urea. Incorporation of broadcast urea increased emissions (16% applied N) by increasing urea hydrolysis relative to surface application. Furthermore, incorporation in band also increased emissions (27% applied N) due to a localized increase in soil pH from 6.0 to 8.7. We conclude that incorporating urea in bands in a dry acidic soil can increase NH(3) volatilization compared to broadcast application followed by incorporation.

Treatment of the syndrome of inappropriate secretion of antidiuretic hormone by urea.

PubMed

Decaux, G; Brimioulle, S; Genette, F; Mockel, J

1980-07-01

Recent data have shown the role of urea in the urinary concentrating mechanism. We studied the effects of exogenous urea administration in hyponatremia associated with the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). In 20 patients with SIADH, we observed a positive correlation between serum sodium and blood urea levels (r = 0.65; p less than 0.01). In one patient with an oat cell carcinoma and SIADH-induced hyponatremia, we observed the same positive correlation (r = 0.80; p less than 0.01) but also a negative one between the excreted fraction of filtered sodium and urinary urea (r = -0.67; p less than 0.001). The short-term administration of low doses of urea (4 to 10 g) resulted in correcting the "salt-losing" tendency of this patient. Longer term administration of high doses of urea (30 g/day) was attempted with the same patient as well as with a healthy volunteer subject with Pitressin-induced SIADH. in both patients, urea treatment lowered urinary sodium excretion as long as hyponatremia was significant (less than 130 meq/liter). Urea treatment also induced a persistent osmotic diuresis, allowing a normal daily intake of water despite SIADH. This was clearly shown during the long-term treatment of a third patient with SIADH who was taking 30 g urea/day during 11 weeks. It is concluded that urea is a good alternative in the treatment of patients with SIADH who presented with persistent hyponatremia despite the restriction of water intake.

Understanding Strategy of Nitrate and Urea Assimilation in a Chinese Strain of Aureococcus anophagefferens through RNA-Seq Analysis

PubMed Central

Dong, Hong-Po; Huang, Kai-Xuan; Wang, Hua-Long; Lu, Song-Hui; Cen, Jing-Yi; Dong, Yue-Lei

2014-01-01

Aureococcus anophagefferens is a harmful alga that dominates plankton communities during brown tides in North America, Africa, and Asia. Here, RNA-seq technology was used to profile the transcriptome of a Chinese strain of A. anophagefferens that was grown on urea, nitrate, and a mixture of urea and nitrate, and that was under N-replete, limited and recovery conditions to understand the molecular mechanisms that underlie nitrate and urea utilization. The number of differentially expressed genes between urea-grown and mixture N-grown cells were much less than those between urea-grown and nitrate-grown cells. Compared with nitrate-grown cells, mixture N-grown cells contained much lower levels of transcripts encoding proteins that are involved in nitrate transport and assimilation. Together with profiles of nutrient changes in media, these results suggest that A. anophagefferens primarily feeds on urea instead of nitrate when urea and nitrate co-exist. Furthermore, we noted that transcripts upregulated by nitrate and N-limitation included those encoding proteins involved in amino acid and nucleotide transport, degradation of amides and cyanates, and nitrate assimilation pathway. The data suggest that A. anophagefferens possesses an ability to utilize a variety of dissolved organic nitrogen. Moreover, transcripts for synthesis of proteins, glutamate-derived amino acids, spermines and sterols were upregulated by urea. Transcripts encoding key enzymes that are involved in the ornithine-urea and TCA cycles were differentially regulated by urea and nitrogen concentration, which suggests that the OUC may be linked to the TCA cycle and involved in reallocation of intracellular carbon and nitrogen. These genes regulated by urea may be crucial for the rapid proliferation of A. anophagefferens when urea is provided as the N source. PMID:25338000

Effect of different ammonia sources on aceticlastic and hydrogenotrophic methanogens.

PubMed

Tian, Hailin; Fotidis, Ioannis A; Kissas, Konstantinos; Angelidaki, Irini

2018-02-01

Ammonium chloride (NH 4 Cl) was usually used as a model ammonia source to simulate ammonia inhibition during anaerobic digestion (AD) of nitrogen-rich feedstocks. However, ammonia in AD originates mainly from degradation of proteins, urea and nucleic acids, which is distinct from NH 4 Cl. Thus, in this study, the inhibitory effect of a "natural" ammonia source (urea) and NH 4 Cl, on four pure methanogenic strains (aceticlastic: Methanosarcina thermophila, Methanosarcina barkeri; hydrogenotrophic: Methanoculleus bourgensis, Methanoculleus thermophilus), was assessed under mesophilic (37 °C) and thermophilic (55 °C) conditions. The results showed that urea hydrolysis increased pH significantly to unsuitable levels for methanogenic growth, while NH 4 Cl had a negligible effect on pH. After adjusting initial pH to 7 and 8, urea was significantly stronger inhibitor with longer lag phases to methanogenesis compared to NH 4 Cl. Overall, urea seems to be more toxic on both aceticlastic and hydrogenotrophic methanogens compared to NH 4 Cl under the same total and free ammonia levels. Copyright © 2017 Elsevier Ltd. All rights reserved.

Synergism effects of pioglitazone and Urtica dioica extract in streptozotocin-induced nephropathy via attenuation of oxidative stress.

PubMed

Shokrzadeh, Mohammad; Sadat-Hosseini, Sara; Fallah, Marjan; Shaki, Fatemeh

2017-05-01

Hyperglycemia promotes oxidative stress that plays a crucial role in the pathogenesis of Diabetic nephropathy (DN). In this study, we investigated the synergism effects of hydroalcoholic extract of Urtica dioica and pioglitazone (PIO) on the prevention of DN in streptozotocin induced-diabetic mice. Forty-two mice were divided into six groups as follows: non-diabetic control group, DMSO group (as solvent), diabetic group and four treatment groups which received U. dioica , pioglitazone, U. dioica plus pioglitazone and vitE. Diabetes was induced by a single dose of streptozotocin (STZ) (200 mg/kg body wt, IP) diluted in citrate buffer (pH= 4.6). After 4 weeks treatment, all animals were anaesthetized and blood was collected for serum urea and creatinine levels assessment in plasma and kidney tissue were excised for evaluation of oxidative stress markers. Treatment with U. dioica significantly inhibited increase in serum urea and creatinine in plasma that were observed in diabetic mice. Furthermore, the elevated level of oxidative stress markers (glutathione oxidation, lipid peroxidation (LPO), protein carbonyl) in renal supernatant of diabetic mice was inhibited by U. dioica treatment. Interestingly, U. dioica promoted beneficial effects of PIO in reducing STZ-induced hyperglycemia, renal damage and oxidative stress markers. Our findings showed that PIO plus U. dioica have synergism protective effects against STZ-induced nephropathy that can be a candidate as a therapeutic approach in order to treatment of DN.

Synergism effects of pioglitazone and Urtica dioica extract in streptozotocin-induced nephropathy via attenuation of oxidative stress

PubMed Central

Shokrzadeh, Mohammad; Sadat-hosseini, Sara; Fallah, Marjan; Shaki, Fatemeh

2017-01-01

Objective(s): Hyperglycemia promotes oxidative stress that plays a crucial role in the pathogenesis of Diabetic nephropathy (DN). In this study, we investigated the synergism effects of hydroalcoholic extract of Urtica dioica and pioglitazone (PIO) on the prevention of DN in streptozotocin induced-diabetic mice. Materials and Methods: Forty-two mice were divided into six groups as follows: non-diabetic control group, DMSO group (as solvent), diabetic group and four treatment groups which received U. dioica, pioglitazone, U. dioica plus pioglitazone and vitE. Diabetes was induced by a single dose of streptozotocin (STZ) (200 mg/kg body wt, IP) diluted in citrate buffer (pH= 4.6). After 4 weeks treatment, all animals were anaesthetized and blood was collected for serum urea and creatinine levels assessment in plasma and kidney tissue were excised for evaluation of oxidative stress markers. Results: Treatment with U. dioica significantly inhibited increase in serum urea and creatinine in plasma that were observed in diabetic mice. Furthermore, the elevated level of oxidative stress markers (glutathione oxidation, lipid peroxidation (LPO), protein carbonyl) in renal supernatant of diabetic mice was inhibited by U. dioica treatment. Interestingly, U. dioica promoted beneficial effects of PIO in reducing STZ-induced hyperglycemia, renal damage and oxidative stress markers. Conclusion: Our findings showed that PIO plus U. dioica have synergism protective effects against STZ-induced nephropathy that can be a candidate as a therapeutic approach in order to treatment of DN. PMID:28656084

Local (gut) and systemic metabolism of rats is altered by consumption of raw bean (Phaseolus vulgaris L var athropurpurea).

PubMed

Santidrián, Santiago; de Moya, Carmen Cavallé; Grant, George; Frühbeck, Gema; Urdaneta, Elena; García, María; Marzo, Florencio

2003-03-01

The composition of the raw legume Phaseolus vulgaris L. var. athropurpurea (PhVa) and its effects on the metabolism of young growing rats have been evaluated. The levels of protein, unsaturated fatty acids, carbohydrate, fibre and bioactive factors present in PhVa were comparable with those in other Phaseolus vulgaris varieties. However, the lectins of PhVa were predominantly of the leucoagglutinating type, and concentrated in the albumin protein fraction. Rats fed a diet (110 g total protein, 16.0 MJ/kg) in which PhVa meal provided about half of the protein excreted high levels of N in faeces and urine, and grew more slowly, than rats fed a high-quality control diet (ad libitum or pair-fed). Small intestine, large intestine and pancreas weights were increased (by almost 100 %, P<0.05), whilst skeletal muscle, thymus and spleen weights were reduced. Blood insulin (16.20 v. 0.50 mU/l, P<0.05, thyroxine, glucose, protein (60.5 v. 48.3 g/l, P<0.05) and LDL-cholesterol were lowered, whilst glucagon (155.3 v. 185.4 ng/l, P<0.05), triiodothyronine and urea were elevated, as were urinary urea, creatinine and glucose. These changes in the local (gut) and systemic metabolism of rats were probably mediated primarily by lectins in PhVa, which were concentrated in the albumin protein fraction, whereas in many other Phaseolus vulgaris lines they are distributed across the globulin and albumin fractions.

Edwardsiella ictaluri Encodes an Acid-Activated Urease That Is Required for Intracellular Replication in Channel Catfish (Ictalurus punctatus) Macrophages▿

PubMed Central

Booth, Natha J.; Beekman, Judith B.; Thune, Ronald L.

2009-01-01

Genomic analysis indicated that Edwardsiella ictaluri encodes a putative urease pathogenicity island containing the products of nine open reading frames, including urea and ammonium transporters. In vitro studies with wild-type E. ictaluri and a ureG::kan urease mutant strain indicated that E. ictaluri is significantly tolerant of acid conditions (pH 3.0) but that urease activity is not required for acid tolerance. Growth studies demonstrated that E. ictaluri is unable to grow at pH 5 in the absence of urea but is able to elevate the environmental pH from pH 5 to pH 7 and grow when exogenous urea is available. Substantial production of ammonia was observed for wild-type E. ictaluri in vitro in the presence of urea at low pH, and optimal activity occurred at pH 2 to 3. No ammonia production was detected for the urease mutant. Proteomic analysis with two-dimensional gel electrophoresis indicated that urease proteins are expressed at both pH 5 and pH 7, although urease activity is detectable only at pH 5. Urease was not required for initial invasion of catfish but was required for subsequent proliferation and virulence. Urease was not required for initial uptake or survival in head kidney-derived macrophages but was required for intracellular replication. Intracellular replication of wild-type E. ictaluri was significantly enhanced when urea was present, indicating that urease plays an important role in intracellular survival and replication, possibly through neutralization of the acidic environment of the phagosome. PMID:19749068

Elevated urinary urea by high-protein diet could be one of the inducements of bladder disorders.

PubMed

Liu, Ming; Li, Min; Liu, Jiangfeng; Wang, Hongkai; Zhong, Dandan; Zhou, Hong; Yang, Baoxue

2016-02-16

Previous work found that urea accumulation in urothelial cells caused by urea transporter B knockout led to DNA damage and apoptosis that contributed to the carcinogenesis. The purpose of this study is to explore the potential connection between high urinary urea concentration and the bladder disorders. A high protein diet rat model was conducted by feeding with 40 % protein diet. In-silico modeling and algorithm, based on the results of microarray and proteomics from the bladder urothelium, were used for the reconstruction of accurate cellular networks and the identification of novel master regulators in the high-protein diet rat model. Pathway and biological process enrichment analysis were used to characterize predicted targets of candidate mRNAs/proteins. The expression pattern of the most significant master regulators was evaluated by qPCR and immunohistochemistry. Based on the analysis of different expressed mRNAs/proteins, 15 significant ones (CRP, MCPT2, MCPT9, EPXH2, SERPING1, SRGN, CDKN1C, CDK6, CCNB1, PCNA, BAX, MAGEB16, SERPINE1, HSPA2, FOS) were highly identified and verified by qPCR and immunohistochemistry. They were involved in immune and inflammatory response, cell cycle arrest, apoptosis and pathways in cancer. These abnormally activated processes caused the bladder interstitial congestion and inflammatory infiltrates under the thinner urothelium, cell desquamation, cytoplasm vacuolization, nucleus swelling and malformation in the high-protein diet group. We provided evidences that high urinary urea concentration caused by high-protein diet might be a potential carcinogenic factor in bladder.

Nanoengineered optical urea biosensor for estimating hemodialysis parameters in spent dialysate.

PubMed

Swati, M; Hase, N K; Srivastava, Rohit

2010-08-31

An optical biosensing scheme based on urease encapsulated calcium alginate microspheres which are coated with polyelectrolyte nanofilms predominantly composed of cresol red (CR) dye is demonstrated in this paper. The dye molecules within the nanofilms are deposited via the layer-by-layer (LbL) self-assembly technique on the microspheres and used as the optical transducer. A flow through cell constructed using a cuvette attached to a fiber optic spectrometer was used to determine the response of the biosensor to standard urea solutions of different concentrations. The change in pH and the absorbance ratio was monitored with time and these results were used for measurements of urea concentrations in the spent dialysate fluid. The biological parameters controlling hemodialysis such as dialyzer clearance or Kt/V and percent removed urea (PRU) have also been reported. The results demonstrate that the urea biosensor is pH reversible with a sensitivity of 0.09 pH units/min and is able to detect a change of 0.005 ratio units in urea concentration ranging 0.1-60 mg dL(-1). The response time of the sensor was calculated as 8 min while the detection range of urea covered the levels that are present in the spent dialysate fluid. The results obtained in the analysis of biological samples were in good agreement with those obtained by a reference method, showing no significant differences at a confidence level of 95%. 2010 Elsevier B.V. All rights reserved.

The structural basis of urea-induced protein unfolding in β-catenin

PubMed Central

Wang, Chao; Chen, Zhongzhou; Hong, Xia; Ning, Fangkun; Liu, Haolin; Zang, Jianye; Yan, Xiaoxue; Kemp, Jennifer; Musselman, Catherine A.; Kutateladze, Tatinna G.; Zhao, Rui; Jiang, Chengyu; Zhang, Gongyi

2014-01-01

Although urea and guanidine hydrochloride are commonly used to denature proteins, the molecular underpinnings of this process have remained unclear for a century. To address this question, crystal structures of β-catenin were determined at various urea concentrations. These structures contained at least 105 unique positions that were occupied by urea molecules, each of which interacted with the protein primarily via hydrogen bonds. Hydrogen-bond competition experiments showed that the denaturing effects of urea were neutralized when polyethylene glycol was added to the solution. These data suggest that urea primarily causes proteins to unfold by competing and disrupting hydrogen bonds in proteins. Moreover, circular-dichroism spectra and nuclear magnetic resonance (NMR) analysis revealed that a similar mechanism caused protein denaturation in the absence of urea at pH levels greater than 12. Taken together, the results led to the conclusion that the disruption of hydrogen bonds is a general mechanism of unfolding induced by urea, high pH and potentially other denaturing agents such as guanidine hydrochloride. Traditionally, the disruption of hydrophobic inter­actions instead of hydrogen bonds has been thought to be the most important cause of protein denaturation. PMID:25372676

The structural basis of urea-induced protein unfolding in β-catenin.

PubMed

Wang, Chao; Chen, Zhongzhou; Hong, Xia; Ning, Fangkun; Liu, Haolin; Zang, Jianye; Yan, Xiaoxue; Kemp, Jennifer; Musselman, Catherine A; Kutateladze, Tatinna G; Zhao, Rui; Jiang, Chengyu; Zhang, Gongyi

2014-11-01

Although urea and guanidine hydrochloride are commonly used to denature proteins, the molecular underpinnings of this process have remained unclear for a century. To address this question, crystal structures of β-catenin were determined at various urea concentrations. These structures contained at least 105 unique positions that were occupied by urea molecules, each of which interacted with the protein primarily via hydrogen bonds. Hydrogen-bond competition experiments showed that the denaturing effects of urea were neutralized when polyethylene glycol was added to the solution. These data suggest that urea primarily causes proteins to unfold by competing and disrupting hydrogen bonds in proteins. Moreover, circular-dichroism spectra and nuclear magnetic resonance (NMR) analysis revealed that a similar mechanism caused protein denaturation in the absence of urea at pH levels greater than 12. Taken together, the results led to the conclusion that the disruption of hydrogen bonds is a general mechanism of unfolding induced by urea, high pH and potentially other denaturing agents such as guanidine hydrochloride. Traditionally, the disruption of hydrophobic interactions instead of hydrogen bonds has been thought to be the most important cause of protein denaturation.

Protective effects of silymarin against acetaminophen-induced hepatotoxicity and nephrotoxicity in mice.

PubMed

Bektur, Nuriye Ezgi; Sahin, Erhan; Baycu, Cengiz; Unver, Gonul

2016-04-01

This study was designed to estimate protective effects of silymarin on acetaminophen (N-acetyl-p-aminophenol, paracetamol; APAP)-induced hepatotoxicity and nephrotoxicity in mice. Treatment of mice with overdose of APAP resulted in the elevation of aspartate aminotransferase (AST), alanine transaminase (ALT), blood urea nitrogen (BUN), and serum creatinine (SCr) levels in serum, liver, and kidney nitric oxide (NO) levels and significant histological changes including decreased body weight, swelling of hepatocytes, cell infiltration, dilatation and congestion, necrosis and apoptosis in liver, and dilatation of Bowman's capsular space and glomerular capillaries, pale-stained tubules epithelium, cell infiltration, and apoptosis in kidney. Posttreatment with silymarin 1 h after APAP injection for 7 days, however, significantly normalized the body weight, histological damage, serum ALT, AST, BUN, SCr, and tissue NO levels. Our observation suggested that silymarin ameliorated the toxic effects of APAP-induced hepatotoxicity and nephrotoxicity in mice. The protective role of silymarin against APAP-induced damages might result from its antioxidative and anti-inflammatory effects. © The Author(s) 2013.

N-acetylcysteine normalizes the urea cycle and DNA repair in cells from patients with Batten disease.

PubMed

Kim, June-Bum; Lim, Nary; Kim, Sung-Jo; Heo, Tae-Hwe

2012-12-01

Batten disease is an inherited disorder characterized by early onset neurodegeneration due to the mutation of the CLN3 gene. The function of the CLN3 protein is not clear, but an association with oxidative stress has been proposed. Oxidative stress and DNA damage play critical roles in the pathogenesis of neurodegenerative diseases. Antioxidants are of interest because of their therapeutic potential for treating neurodegenerative diseases. We tested whether N-acetylcysteine (NAC), a well-known antioxidant, improves the pathology of cells from patients with Batten disease. At first, the expression levels of urea cycle components and DNA repair enzymes were compared between Batten disease cells and normal cells. We used both mRNA expression levels and Western blot analysis. We found that carbamoyl phosphate synthetase 1, an enzyme involved in the urea cycle, 8-oxoguanine DNA glycosylase 1 and DNA polymerase beta, enzymes involved in DNA repair, were expressed at higher levels in Batten disease cells than in normal cells. The treatment of Batten disease cells with NAC for 48 h attenuated activities of the urea cycle and of DNA repair, as indicated by the substantially decreased expression levels of carbamoyl phosphate synthetase 1, 8-oxoguanine DNA glycosylase 1 and DNA polymerase beta proteins compared with untreated Batten cells. NAC may serve in alleviating the burden of urea cycle and DNA repair processes in Batten disease cells. We propose that NAC may have beneficial effects in patients with Batten disease. Copyright © 2012 John Wiley & Sons, Ltd.

Biochemical and immunological changes on oral glutamate feeding in male albino rats

NASA Astrophysics Data System (ADS)

Kumar, D.; Bansal, Anju; Thomas, Pauline; Sairam, M.; Sharma, S. K.; Mongia, S. S.; Singh, R.; Selvamurthy, W.

High altitude stress leads to lipid peroxidation and free radical formation which results in cell membrane damage in organs and tissues, and associated mountain diseases. This paper discusses the changes in biochemical parameters and antibody response on feeding glutamate to male albino Sprague Dawley rats under hypoxic stress. Exposure of rats to simulated hypoxia at 7576 m, for 6 h daily for 5 consecutive days, in an animal decompression chamber at 32+/-2° C resulted in an increase in plasma malondialdehyde level with a concomitant decrease in blood glutathione (reduced) level. Supplementation of glutamate orally at an optimal dose (27 mg/kg body weight) in male albino rats under hypoxia enhanced glutathione level and decreased malondialdehyde concentration significantly. Glutamate feeding improved total plasma protein and glucose levels under hypoxia. The activities of serum glutamate oxaloacetate transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) and the urea level remained elevated on glutamate supplementation under hypoxia. Glutamate supplementation increased the humoral response against sheep red blood cells (antibody titre). These results indicate a possible utility of glutamate in the amelioration of hypoxia-induced oxidative stress.

Elevated levels of plasma uric acid and its relation to hypertension in arsenic-endemic human individuals in Bangladesh

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huda, Nazmul; Department of Medicine, Rajshahi Medical College, Rajshahi 6000; Hossain, Shakhawoat

Blood uric acid has been recognized as a putative marker for cardiovascular diseases (CVDs). CVDs are the major causes of arsenic-related morbidity and mortality. However, the association of arsenic exposure with plasma uric acid (PUA) levels in relation to CVDs has not yet been explored. This study for the first time demonstrated the associations of arsenic exposure with PUA levels and its relationship with hypertension. A total of 483 subjects, 322 from arsenic-endemic and 161 from non-endemic areas in Bangladesh were recruited as study subjects. Arsenic concentrations in the drinking water, hair and nails of the study subjects were measuredmore » by inductively coupled plasma mass spectroscopy. PUA levels were measured using a colorimetric method. We found that PUA levels were significantly (p < 0.001) higher in males and females living in arsenic-endemic areas than those in non-endemic area. Arsenic exposure (water, hair and nail arsenic) levels showed significant positive correlations with PUA levels. In multiple regression analyses, arsenic exposure levels were found to be the most significant contributors on PUA levels among the other variables that included age, body mass index, blood urea nitrogen, and smoking. There were dose–response relationships between arsenic exposure and PUA levels. Furthermore, diastolic and systolic blood pressure showed significant positive correlations with PUA levels. Finally, the average PUA levels were significantly higher in the hypertensive group than those in the normotensive group in both males and females living in arsenic-endemic areas. These results suggest that arsenic exposure-related elevation of PUA levels may be implicated in arsenic-induced CVDs. - Highlights: • PUA levels were higher in arsenic-endemic subjects than in non-endemic subjects. • Drinking water, hair and nail arsenic showed significant associations with PUA levels. • Drinking water, hair and nail arsenic showed dose–response relationships with PUA. • Arsenic-endemic hypertensive study subjects had elevated levels of PUA. • Increased PUA levels may be implicated in arsenic-induced CVDs.« less

Validation of the salivary urea and creatinine tests as screening methods of chronic kidney disease in Vietnamese patients.

PubMed

Pham, Thuy Anh Vu

2017-11-01

The aims of this case control study were to correlate the serum and salivary urea as well as creatinine levels; and to evaluate salivary urea and creatinine as noninvasive alternatives to serum for creatinine estimation in chronic kidney disease (CKD) patients. Blood and saliva samples were collected from 112 CKD patients and 108 subjects without CKD for quantitative analysis of urea and creatinine. Spearman's correlation coefficients between salivary and serum urea as well as creatinine were obtained. Receiver operating characteristic analysis was done to assess the diagnostic tests of salivary urea and creatinine. Cut-off values were determined based on the best trade-off between the sensitivity and specificity for both salivary urea and creatinine. Salivary urea and creatinine concentrations were significantly higher in CKD patients than those in control subjects; and increased by the stages of the severity of the disease. The positive correlation was significantly found between salivary and serum creatinine (r  =  0.90) and between salivary and serum urea (r  =  0.73). Area under the curve for salivary urea was 0.76 and a cut-off value of 14.25 mmol/L gave a sensitivity of 82.9% and specificity of 57.8%. Area under the curve for salivary creatinine was 0.92 and a cut-off value of 0.24 mg/dL gave a sensitivity of 86.5% and specificity of 87.2%. Both salivary urea and creatinine have a high capacity for serum creatinine estimation. Salivary urea and creatinine tests can be used as low-cost, easily accessible and noninvasive tools for screening, diagnosing, monitoring treatment outcomes and ascertaining prognosis of chronic kidney disease.

Interactions of S-peptide analogue in aqueous urea and trimethylamine-N-oxide solutions: A molecular dynamics simulation study

NASA Astrophysics Data System (ADS)

Sarma, Rahul; Paul, Sandip

2013-07-01

The ability of the osmolyte, trimethylamine-N-oxide (TMAO), to protect proteins from deleterious effect of urea, another commonly available osmolyte, is well-established. However, the molecular mechanism of this counteraction is not understood yet. To provide a molecular level understanding of how TMAO protects proteins in highly concentrated urea solution, we report here molecular dynamics simulation results of a 15-residue model peptide in two different conformations: helix and extended. For both conformations, simulations are carried out in pure water as well as in binary and ternary aqueous solutions of urea and TMAO. Analysis of solvation characteristics reveals direct interactions of urea and TMAO with peptide residues. However, the number of TMAO molecules that enter in the first solvation shell of the peptide is significantly lower than that of urea, and, unlike water and urea, TMAO shows its inability to form hydrogen bond with backbone oxygen and negatively charged sidechains. Preferential accumulation of urea near the peptide surface and preferential exclusion of TMAO from the peptide surface are observed. Inclusion of osmolytes in the peptide solvation shell leads to dehydration of the peptide in binary and ternary solutions of urea and TMAO. Solvation of peptide residues are investigated more closely by calculating the number of hydrogen bonds between the peptide and solution species. It is found that number of hydrogen bonds formed by the peptide with solution species increases in binary urea solution (relative to pure water) and this relative enhancement in hydrogen bond number reduces upon addition of TMAO. Our simulation results also suggest that, in the ternary solution, the peptide solvation layer is better mixed in terms of water and urea as compared to binary urea solution. Implications of the results for counteraction mechanism of TMAO are discussed.

Antagonism at combined effects of chemical fertilizers and carbamate insecticides on the rice-field N2-fixing cyanobacterium Cylindrospermum sp. in vitro

PubMed Central

Nayak, Nabakishore; Rath, Shakti

2014-01-01

Effects of chemical fertilizers (urea, super phosphate and potash) on toxicities of two carbamate insecticides, carbaryl and carbofuran, individually to the N2-fixing cyanobacterium, Cylindrospermum sp. were studied in vitro at partially lethal levels (below highest permissive concentrations) of each insecticide. The average number of vegetative cells between two polar heterocysts was 16.3 in control cultures, while the mean value of filament length increased in the presence of chemical fertilizers, individually. Urea at the 10 ppm level was growth stimulatory and at the 50 ppm level it was growth inhibitory in control cultures, while at 100 ppm it was antagonistic, i.e. toxicity-enhancing along with carbaryl, individually to the cyanobacterium, antagonism was recorded. Urea at 50 ppm had toxicity reducing effect with carbaryl or carbofuran. At 100 and 250 ppm carbofuran levels, 50 ppm urea only had a progressive growth enhancing effect, which was marked well at 250 ppm carbofuran level, a situation of synergism. Super phosphate at the 10 ppm level only was growth promoting in control cultures, but it was antagonistic at its higher levels (50 and 100 ppm) along with both insecticides, individually. Potash (100, 200, 300 and 400 ppm) reduced toxicity due to carbaryl 20 and carbofuran 250 ppm levels, but potash was antagonistic at the other insecticide levels. The data clearly showed that the chemical fertilizers used were antagonistic with both the insecticides during toxicity to Cylindrospermum sp. PMID:26038669

Neurological implications of urea cycle disorders

PubMed Central

Summar, M.; Leonard, J. V.

2013-01-01

Summary The urea cycle disorders constitute a group of rare congenital disorders caused by a deficiency of the enzymes or transport proteins required to remove ammonia from the body. Via a series of biochemical steps, nitrogen, the waste product of protein metabolism, is removed from the blood and converted into urea. A consequence of these disorders is hyperammonaemia, resulting in central nervous system dysfunction with mental status changes, brain oedema, seizures, coma, and potentially death. Both acute and chronic hyperammonaemia result in alterations of neurotransmitter systems. In acute hyperammonaemia, activation of the NMDA receptor leads to excitotoxic cell death, changes in energy metabolism and alterations in protein expression of the astrocyte that affect volume regulation and contribute to oedema. Neuropathological evaluation demonstrates alterations in the astrocyte morphology. Imaging studies, in particular 1H MRS, can reveal markers of impaired metabolism such as elevations of glutamine and reduction of myoinositol. In contrast, chronic hyperammonaemia leads to adaptive responses in the NMDA receptor and impairments in the glutamate–nitric oxide–cGMP pathway, leading to alterations in cognition and learning. Therapy of acute hyperammonaemia has relied on ammonia-lowering agents but in recent years there has been considerable interest in neuroprotective strategies. Recent studies have suggested restoration of learning abilities by pharmacological manipulation of brain cGMP with phosphodiesterase inhibitors. Thus, both strategies are intriguing areas for potential investigation in human urea cycle disorders. PMID:18038189

The diuretic effect of urea analog dimethylthiourea in female Wistar rats.

PubMed

Cil, O; Ertunc, M; Onur, R

2012-10-01

Urea plays an important role in the urinary concentrating mechanism in the kidney by contributing greatly in the generation of hyperosmolar medulla due to the presence of urea transporters, which mediate facilitated transport of urea. In this study, we investigated the possible diuretic effect of urea analog and urea transporter inhibitor, dimethylthiourea (DMTU), in rats. Female Wistar rats were divided into two groups, group 1 (control group, n = 7) rats were injected with saline intraperitoneally (i.p.), while group 2 (DMTU group, n = 7) rats were injected with 500 mg/kg DMTU (i.p.) and an additional dose of 125 mg/kg DMTU after 8 h. DMTU administration induced an approximately three times increase in daily urine volume (p < 0.001) and decreased urine osmolality to approximately 35% of controls (p < 0.0001). DMTU also increased free water clearance (p < 0.0001) without a significant change in osmolar clearance. DMTU treatment caused an increase in urea clearance (p < 0.05) and fractional excretion of urea (p < 0.05) with a decrease in serum urea concentration (p < 0.001). DMTU had no effect on creatinine clearance or serum electrolytes, creatinine levels and osmolality. With these findings, we report for the first time that DMTU has a prominent diuretic effect with increased urea excretion, which may be explained by the inhibitory effect of the drug on urea transporters. Our findings suggest that DMTU may be used as a diuretic agent and also could be used as a lead compound for the development of novel diuretics.

Newborn screening for proximal urea cycle disorders: Current evidence supporting recommendations for newborn screening.

PubMed

Merritt, J Lawrence; Brody, Linnea L; Pino, Gisele; Rinaldo, Piero

2018-04-20

Current newborn screening (NBS) for urea cycle disorders (UCD) is incomplete as only distal UCDs are included in most NBS programs by measuring elevated amino acid concentrations. NBS for the proximal UCDs involves the detection in NBS spots of low citrulline values, a finding which is often overlooked because it is considered to be inadequate. We retrospectively analyzed NBS blood spots from known UCD patients comparing the utility of the Region 4 Stork (R4S) interpretive tools to conventional cutoff based interpretation. This study shows the utility of R4S tools in detecting all UCDs, and provides evidence to support the nomination to add proximal UCDs to the recommended uniform screening panel. Copyright © 2018 Elsevier Inc. All rights reserved.

Daily rhythm of salivary and serum urea concentration in sheep

PubMed Central

Piccione, Giuseppe; Foà, Augusto; Bertolucci, Cristiano; Caola, Giovanni

2006-01-01

Background In domestic animals many biochemical and physiological processes exhibit daily rhythmicity. The aim of the present study was to investigate the rhythmic pattern of salivary and serum urea concentrations in sheep. Methods Six 3-year-old female sheep kept in the same environmental conditions were used. Sheep were sampled at 4 hour intervals for 48 consecutive hours starting at 08:00 of the first day and finishing at 04:00 of the second day. Blood samples were collected via intravenous cannulae inserted into the jugular vein; saliva samples were collected through a specific tube, the "Salivette". Salivary and serum urea concentrations were assayed by means of UV spectrophotometer. ANOVA was used to determine significant differences. The single Cosinor procedure was applied to the results showing significant differences over time. Results ANOVA showed a significant effect of time on salivary and serum urea concentrations. Serum and salivary urea peaked during the light phase. In the dark phase serum and salivary urea concentrations decreased, and the diurnal trough occurred at midnight. Cosinor analysis showed diurnal acrophases for salivary and serum urea concentrations. Daily mean levels were significantly higher in the serum than in the saliva. Conclusion In sheep both salivary and serum urea concentrations showed daily fluctuations. Urea is synthesized in the liver and its production is strongly influenced by food intake. Future investigation should clarify whether daily urea rhythms in sheep are endogenous or are simply the result of the temporal administration of food. PMID:17123442

Aggravation of cyclophosphamide-induced acute neurological disorders under conditions of artificial acidification of chyme in rats.

PubMed

Schaefer, T V; Rejuniuk, V L; Malakhovsky, V N; Ivnitsky, Ju Ju

2012-10-01

The effect of artificial acidification of the intestinal content on neurological manifestations of acute severe cyclophosphamide intoxication was studied in rats. The animals were gavaged with 20 ml/kg sulfuric (0.05 M), hydrochloric, boric, or lactic acids (0.1 M) 3 h before intraperitoneal injections of the cytostatic in doses of 0, 200, 600, or 1000 mg/kg. The decrease in pH (by.0) and ammonia-producing activity of the cecal chyme developed within 3 h after administration of acids. Cyclophosphamide caused hyperammonemia; glutamine/ammonia and urea/ammonia ratios in the blood decreased. These changes augmented after administration of acids (boric acid produced maximum and lactic acid minimum effects). Acid treatment resulted in greatest elevation of ammonia level in the portal venous blood and a lesser elevation in the vena cava posterior blood. Acid treatment promoted manifestation of cyclophosphamide neurotoxic effect and animal death. Hence, acidification of the chyme inhibited the formation of ammonia in it, while ammonia release from the gastrointestinal tract into the blood increased; the treatment augmented hyperammonemia and aggravated the neurological manifestations of cyclophosphamide intoxication.

Nitrogen digestion and urea recycling in Hokkaido native horses fed hay-based diets.

PubMed

Obitsu, Taketo; Hata, Hiroshi; Taniguchi, Kohzo

2015-02-01

Nitrogen (N) digestion and urea-N metabolism in Hokkaido native horses fed roughage-based diets containing different types and levels of protein sources were studied. Horses (173 ± 4.8 kg) fitted with an ileum cannula were fed four diets consisting of 100% timothy hay (TH), 88% TH and 12% soybean meal (SBM), 79% TH and 21% SBM, and 51% TH and 49% alfalfa hay at 2.2% of body weight. Dietary protein content varied from 5% to 15% of dry matter. Apparent N digestibilities in the pre-cecum and total tract for the TH diet were lower than those for other diets. However, the proportion of post-ileum N digestion to N intake was not affected by the diets. Urea-N production was linearly related to N intake, but gut urea-N entry was not affected by the diets. The proportion of gut urea-N entry to urea-N production tended to be higher for the TH diet (57%) than the two SBM diets (39%). Anabolic use of urea-N entering the gut was not affected by the diets (20-36% of gut urea-N entry). These results indicate that urea-N recycling provides additional N sources for microbial fermentation in the hindgut of Hokkaido native horses fed low-quality roughages. © 2014 Japanese Society of Animal Science.

Prevalence of Helicobacter Pylori in Gastric Fluid in the Surgical Patient

DTIC Science & Technology

1998-01-01

of five percent. This percentage closely matches the oxygen level found in the stomach’s mucous layer . It has an electropositive internal milieu which...amounts of urease which cleaves urea into ammonia and carbon dioxide. The presence of urease is one of the biochemical markers used to help identify...in acidic gastric juice where small amounts of urea are present. Helicobacter pylorl produces urease which breaks down the urea and produces ammonia

Suppression of nitrification and N2O emission by karanjin--a nitrification inhibitor prepared from karanja (Pongamia glabra Vent.).

PubMed

Majumdar, Deepanjan

2002-06-01

A laboratory incubation study was undertaken to study nitirification and N2O emission in an alluvial, sandy loam soil (typic ustochrept), fertilized with urea and urea combined with different levels of two nitrification inhibitors viz. karanjin and dicyandiamide (DCD). Karanjin [a furanoflavonoid, obtained from karanja (Pongamia glabra Vent.) seeds] and DCD were incorporated at the rate of 5%, 10%, 15%, 20% and 25% of applied urea-N (100 mg kg(-1) soil), to the soil (100 g) adjusted to field capacity moisture content. Mean N2O flux was appreciably reduced on addition of the inhibitors with urea. Amounts of nitrified N (i.e. (NO3- + NO2-)-N) in total inorganic N (i.e. (NO3 + NO2- + NH4+)-N) in soil were found to be much lower on the addition of karanjin with urea (2-8%) as compared to urea plus DCD (14-66%) during incubation, indicating that karanjin was much more potent nitrification inhibitor than DCD. Nitrification inhibition was appreciable on the application of different levels of karanjin (62-75%) and DCD (9-42%). Cumulative N2O-N loss was found to be in the range of 0.5-80% of the nitrified N at different stages of incubation. Application of karanjin resulted in higher mitigation of total N2O-N emission (92-96%) when compared with DCD (60-71%).

Absolute and Relative Carnitine Deficiency in Patients on Hemodialysis and Peritoneal Dialysis.

PubMed

Naseri, Mitra; Mottaghi Moghadam Shahri, Hasan; Horri, Mohsen; Esmaeeli, Mohammad; Ghaneh Sherbaf, Fatemeh; Jahanshahi, Shohre; Moeenolroayaa, Giti; Rasoli, Zahra; Salemian, Farzaneh; Pour Hasan, Maryam

2016-01-01

Carnitine deficiency is commonly seen in dialysis patients. This study assessed the association dialysis and pediatric patients' characteristics with plasma carnitines levels. Plasma carnitine concentrations were measured by tandem mass spectrometry in 46 children on hemodialysis or peritoneal dialysis. The total carnitine, free carnitine (FC), and L-acyl carnitine (AC) levels of 40 µmol/L and less, less than 7 µmol/L, and less than 15 µmol/L were defined low, respectively. An FC less than 20 µmol/L and an AC/FC ratio greater than 0.4 were considered as absolute and relative carnitine deficiencies. The correlation between carnitines levels and AC/FC ratio and age, duration of dialysis, characteristics of dialysis, and blood urea nitrogen and serum albumin concentrations were assessed. Absolute carnitine deficiency, low total carnitine, and low AC concentrations were found in 66.7%, 82.6%, and 51% of the patients, respectively. All of the patients had relative carnitine deficiency. Carnitine measurements were not significantly different between the hemodialysis and peritoneal dialysis groups. More severe relative carnitine deficiency was found in those with lower blood urea nitrogen levels and those on peritoneal dialysis. No linear correlation was found between carnitine levels and age, duration of dialysis, characteristics of dialysis, serum albumin level, or blood urea nitrogen level. Absolute and relative carnitine deficiencies are common among children on dialysis. Patients with lower blood urea nitrogen levels and peritoneal dialysis patients are more prone to severe relative carnitine deficiency.

Nitrogen metabolism, acid-base regulation, and molecular responses to ammonia and acid infusions in the spiny dogfish shark (Squalus acanthias).

PubMed

Nawata, C Michele; Walsh, Patrick J; Wood, Chris M

2015-07-01

Although they are ureotelic, marine elasmobranchs express Rh glycoproteins, putative ammonia channels. To address questions raised by a recent study on high environmental ammonia (HEA) exposure, dogfish were intravascularly infused for 24 h at 3 ml kg(-1) h(-1) with isosmotic NaCl (500 mmol l(-1), control), NH4HCO3 (500 mmol l(-1)), NH4Cl (500 mmol l(-1)), or HCl (as 125 mmol l(-1) HCl + 375 mmol l(-1) NaCl). While NaCl had no effect on arterial acid-base status, NH4HCO3 caused mild alkalosis, NH4Cl caused strong acidosis, and HCl caused lesser acidosis, all predominantly metabolic in nature. Total plasma ammonia (T(Amm)) and excretion rates of ammonia (J(Amm)) and urea-N (J(Urea-N)) were unaffected by NaCl or HCl. However, despite equal loading rates, plasma T(Amm) increased to a greater extent with NH4Cl, while J(Amm) increased to a greater extent with NH4HCO3 due to much greater increases in blood-to-water PNH3 gradients. As with HEA, both treatments caused large (90%) elevations of J(Urea-N), indicating that urea-N synthesis by the ornithine-urea cycle (OUC) is driven primarily by ammonia rather than HCO3(-). Branchial mRNA expressions of Rhbg and Rhp2 were unaffected by NH4HCO3 or NH4Cl, but v-type H(+)-ATPase was down-regulated by both treatments, and Rhbg and Na(+)/H(+) exchanger NHE2 were up-regulated by HCl. In the kidney, Rhbg was unresponsive to all treatments, but Rhp2 was up-regulated by HCl, and the urea transporter UT was up-regulated by HCl and NH4Cl. These responses are discussed in the context of current ideas about branchial, renal, and OUC function in this nitrogen-limited predator.

Effect of perfusate hematocrit on urea permeability-surface area in isolated dog lung

DOE Office of Scientific and Technical Information (OSTI.GOV)

Parker, R.E.; Roselli, R.J.; Haselton, F.R.

1986-10-01

Seven dog lower left lung lobes were statically inflated and perfused at a constant rate for each lobe with a perfusate in which the hematocrit was altered over a wide range. The permeability-surface area of urea was calculated from multiple indicator dilution curves using two separate injectates for each hematocrit level. One injectate contained only /sup 125/I-albumin as the vascular reference tracer and the other contained both /sup 51/Cr-erythrocytes and /sup 125/I-albumin as the vascular reference tracers; both contained (/sup 14/C)urea as the permeating tracer. The results strongly indicate that the phenomenon of erythrocyte trapping of urea does not affectmore » the calculation of urea permeability-surface area product provided the appropriate albumin-erythrocyte composite reference tracer is utilized in its calculation.« less

Monitoring of urea and potassium by reverse iontophoresis in vitro.

PubMed

Wascotte, Valentine; Delgado-Charro, M Begoña; Rozet, Eric; Wallemacq, Pierre; Hubert, Philippe; Guy, Richard H; Préat, Véronique

2007-06-01

Reverse iontophoresis is an alternative to blood sampling for the monitoring of endogenous molecules. Here, the potential of the technique to measure urea and potassium levels non-invasively, and to track their concentrations during hemodialysis, has been examined. In vitro experiments were performed to test (a) a series of subdermal urea and potassium concentrations typical of the pathophysiologic range, and (b) a decreasing profile of urea and potassium subdermal concentrations to mimic those which are observed during hemodialysis. (a) After 60-120 min of iontophoresis, linear relationships (p < 0.05) were established between both urea and potassium fluxes and their respective subdermal concentrations. The determination coefficients were above 0.9 after 1 h of current passage using sodium as an internal standard. (b) Reverse iontophoretic fluxes of urea and K(+) closely paralleled the decay of the respective concentrations in the subdermal compartment, as would occur during a hemodialysis session. These in vitro experiments demonstrate that urea and potassium can be quantitatively and proportionately extracted by reverse iontophoresis, even when the subdermal concentrations of the analytes are varying with time. These results suggest the non-invasive monitoring of urea and potassium to diagnose renal failure and during hemodialysis is feasible, and that in vivo measurements are warranted.

The ygeW encoded protein from Escherichia coli is a knotted ancestral catabolic transcarbamylase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Yongdong; Jin, Zhongmin; Yu, Xiaolin

Purine degradation plays an essential role in nitrogen metabolism in most organisms. Uric acid is the final product of purine catabolism in humans, anthropoid apes, birds, uricotelic reptiles, and almost all insects. Elevated levels of uric acid in blood (hyperuricemia) cause human diseases such as gout, kidney stones, and renal failure. Although no enzyme has been identified that further degrades uric acid in humans, it can be oxidized to produce allantoin by free-radical attack. Indeed, elevated levels of allantoin are found in patients with rheumatoid arthritis, chronic lung disease, bacterial meningitis, and noninsulin-dependent diabetes mellitus. In other mammals, some insectsmore » and gastropods, uric acid is enzymatically degraded to the more soluble allantoin through the sequential action of three enzymes: urate oxidase, 5-hydroxyisourate (HIU) hydrolase and 2-oxo-4-hydroxy-4-carboxy-5-ureidoimidazoline (OHCU) decarboxylase. Therefore, an elective treatment for acute hyperuricemia is the administration of urate oxidase. Many organisms, including plants, some fungi and several bacteria, are able to catabolize allantoin to release nitrogen, carbon, and energy. In Arabidopsis thaliana and Eschrichia coli, S-allantoin has recently been shown to be degraded to glycolate and urea by four enzymes: allantoinase, allantoate amidohydrolase, ureidoglycine aminohydrolase, and ureidoglycolate amidohydrolase.« less

Plasma circulating fibrinogen stability and moderate beer consumption.

PubMed

Gorinstein, Shela; Caspi, Abraham; Zemser, Marina; Libman, Imanuel; Goshev, Ivan; Trakhtenberg, Simon

2003-12-01

MODERATE BEER CONSUMPTION (MBC) IS CARDIOPROTECTIVE: it positively influences plasma lipid levels and plasma antioxidant activity in beer-consuming individuals. The connection between MBC and blood coagulation is not clearly defined. Forty-two volunteers were equally divided into experimental (EG) and control (CG) groups following coronary bypass surgery. For 30 consecutive days, only patients of the EG consumed 330 mL of beer per day (about 20 g of alcohol). A comprehensive clinical investigation of 42 patients was done. Blood samples were collected before and after the investigation for a wide range of laboratory tests. The plasma fibrinogen was denatured with 8 M urea and intrinsic fluorescence (IF), hydrophobicity and differential scanning calorimetry (DSC) were used to reveal possible qualitative changes. After 30 days of moderate beer consumption, positive changes in the plasma lipid levels, plasma anticoagulant and plasma antioxidant activities were registered in patients of the EG group. In 17 out of 21 patients of the same group, differences in plasma circulating fibrinogen's (PCF), secondary and tertiary structures were found. The stability of fibrinogen, expressed in thermodynamic parameters, has shown that the loosening of the structure takes place under ethanol and urea denaturation. Also fluorescence stability of PCF was decreased. No changes in the lipid levels, anticoagulant and antioxidant activity or changes in PCF were detected in patients of CG. In conclusion, for the first time after a short term of moderate beer consumption some qualitative changes in the plasma circulating fibrinogen were detected: differences in the emission peak response, fluorescence intensity and all thermodynamic data. Together, with the decrease in the PCF concentration it may lead to an elevation of the blood anticoagulant activity.

Dapagliflozin Aggravates Renal Injury via Promoting Gluconeogenesis in db/db Mice.

PubMed

Jia, Yingli; He, Jinzhao; Wang, Liang; Su, Limin; Lei, Lei; Huang, Wei; Geng, Xiaoqiang; Zhang, Shun; Meng, Xiaolu; Zhou, Hong; Yang, Baoxue

2018-01-01

A sodium-glucose co-transporter-2 inhibitor dapagliflozin is widely used for lowering blood glucose and its usage is limited in type 2 diabetes mellitus patients with moderate renal impairment. As its effect on kidney function is discrepant and complicated, the aim of this study is to determine the effect of dapagliflozin on the progression of diabetic nephropathy and related mechanisms. Twelve-week-old male C57BL/6 wild-type and db/db mice were treated with vehicle or 1 mg/kg dapagliflozin for 12 weeks. Body weight, blood glucose, insulin tolerance, glucose tolerance, pyruvate tolerance and 24-hour urine were measured every 4 weeks. At 24 weeks of age, renal function was evaluated by blood urea nitrogen level, creatinine clearance, urine output, urinary albumin excretion, Periodic Acid-Schiff staining, Masson's trichrome staining and electron microscopy. Changes in insulin signaling and gluconeogenic key regulatory enzymes were detected using Western blot analysis. Dapagliflozin did not alleviate but instead aggravated diabetic nephropathy manifesting as increased levels of microalbuminuria, blood urea nitrogen, and glomerular and tubular damage in db/db mice. Despite adequate glycemic control by dapagliflozin, urinary glucose excretion increased after administration before 24 weeks of age and was likely associated with renal impairment. Increased urinary glucose excretion was mainly derived from the disturbance of glucose homeostasis with elevated hepatic and renal gluconeogenesis induced by dapagliflozin. Although it had no effect on insulin sensitivity and glucose tolerance, dapagliflozin further induced the expression of gluconeogenic key rate-limiting enzymes through increasing the expression levels of FoxO1 in the kidney and liver. These experimental results indicate that dapagliflozin aggravates diabetes mellitus-induced kidney injury, mostly through increasing gluconeogenesis. © 2018 The Author(s). Published by S. Karger AG, Basel.

Cloning and characterization of aquaglyceroporin genes from rainbow smelt (Osmerus mordax) and transcript expression in response to cold temperature.

PubMed

Hall, Jennifer R; Clow, Kathy A; Rise, Matthew L; Driedzic, William R

2015-09-01

Aquaglyceroporins (GLPs) are integral membrane proteins that facilitate passive movement of water, glycerol and urea across cellular membranes. In this study, GLP-encoding genes were characterized in rainbow smelt (Osmerus mordax mordax), an anadromous teleost that accumulates high glycerol and modest urea levels in plasma and tissues as an adaptive cryoprotectant mechanism in sub-zero temperatures. We report the gene and promoter sequences for two aqp10b paralogs (aqp10ba, aqp10bb) that are 82% identical at the predicted amino acid level, and aqp9b. Aqp10bb and aqp9b have the 6 exon structure common to vertebrate GLPs. Aqp10ba has 8 exons; there are two additional exons at the 5' end, and the promoter sequence is different from aqp10bb. Molecular phylogenetic analysis suggests that the aqp10b paralogs arose from a gene duplication event specific to the smelt lineage. Smelt GLP transcripts are ubiquitously expressed; however, aqp10ba transcripts were highest in kidney, aqp10bb transcripts were highest in kidney, intestine, pyloric caeca and brain, and aqp9b transcripts were highest in spleen, liver, red blood cells and kidney. In cold-temperature challenge experiments, plasma glycerol and urea levels were significantly higher in cold- compared to warm-acclimated smelt; however, GLP transcript levels were generally either significantly lower or remained constant. The exception was significantly higher aqp10ba transcript levels in kidney. High aqp10ba transcripts in smelt kidney that increase significantly in response to cold temperature in congruence with plasma urea suggest that this gene duplicate may have evolved to allow the re-absorption of urea to concomitantly conserve nitrogen and prevent freezing. Copyright © 2015 Elsevier Inc. All rights reserved.

Response to fasting in an unnaturally obese carnivore, the captive European polecat Mustela putorius.

PubMed

Mustonen, Anne-Mari; Puukka, Matti; Rouvinen-Watt, Kirsti; Aho, Jari; Asikainen, Juha; Nieminen, Petteri

2009-11-01

The European polecat (Mustela putorius) is a naturally lean carnivore prone to excessive weight gain in captivity. This study assessed its suitability to investigate the natural history of the obese phenotype displayed in overweight humans, domestic animals, and seasonally obese wild mammals. Ten farm-bred polecats were subjected to a 5-day fast with 10 controls. Obesity (40% body fat) was associated with an unfavorable plasma lipid profile and high glucose and insulin concentrations. The polecats were in phase II of fasting with normoglycemia, low liver carbohydrate stores, and decreased plasma concentrations of urea and most amino acids. Although the plasma nonesterified fatty acid (NEFA) levels were elevated, the adipose tissue lipase activities suggested a blunted lipolytic response. Lipid mobilization was more efficient from intraabdominal fat. The animals developed hepatic lipidosis with elevated NEFA influx into the liver and losses of n-3 polyunsaturated fatty acids and arginine as hypothetical etiological factors. The plasma leptin, insulin, and triiodothyronine levels decreased but were not accompanied by reduced sex steroid or increased stress hormone concentrations. The blunted lipolytic response often encountered in obesity suggests that the organism is trying to defend the obese phenotype. Liver lipidosis and decreased insulin and triiodothyronine levels seem to be among the most consistent responses to fasting manifested in diverse mammalian orders and different levels of body fatness. The polecat could be recommended as an easily accessible carnivorean model to study the natural history of the obese phenotype and its comorbidities.

In vivo monitoring of urea cycle activity with (13)C-acetate as a tracer of ureagenesis.

PubMed

Opladen, Thomas; Lindner, Martin; Das, Anibh M; Marquardt, Thorsten; Khan, Aneal; Emre, Sukru H; Burton, Barbara K; Barshop, Bruce A; Böhm, Thea; Meyburg, Jochen; Zangerl, Kathrin; Mayorandan, Sebene; Burgard, Peter; Dürr, Ulrich H N; Rosenkranz, Bernd; Rennecke, Jörg; Derbinski, Jens; Yudkoff, Marc; Hoffmann, Georg F

2016-01-01

The hepatic urea cycle is the main metabolic pathway for detoxification of ammonia. Inborn errors of urea cycle function present with severe hyperammonemia and a high case fatality rate. Long-term prognosis depends on the residual activity of the defective enzyme. A reliable method to estimate urea cycle activity in-vivo does not exist yet. The aim of this study was to evaluate a practical method to quantify (13)C-urea production as a marker for urea cycle function in healthy subjects, patients with confirmed urea cycle defect (UCD) and asymptomatic carriers of UCD mutations. (13)C-labeled sodium acetate was applied orally in a single dose to 47 subjects (10 healthy subjects, 28 symptomatic patients, 9 asymptomatic carriers). The oral (13)C-ureagenesis assay is a safe method. While healthy subjects and asymptomatic carriers did not differ with regards to kinetic variables for urea cycle flux, symptomatic patients had lower (13)C-plasma urea levels. Although the (13)C-ureagenesis assay revealed no significant differences between individual urea cycle enzyme defects, it reflected the heterogeneity between different clinical subgroups, including male neonatal onset ornithine carbamoyltransferase deficiency. Applying the (13)C-urea area under the curve can differentiate between severe from more mildly affected neonates. Late onset patients differ significantly from neonates, carriers and healthy subjects. This study evaluated the oral (13)C-ureagenesis assay as a sensitive in-vivo measure for ureagenesis capacity. The assay has the potential to become a reliable tool to differentiate UCD patient subgroups, follow changes in ureagenesis capacity and could be helpful in monitoring novel therapies of UCD. Copyright © 2015 Elsevier Inc. All rights reserved.

[Effects of thiourea on pH and availability of metal ions in acid red soil].

PubMed

Yang, Bo; Wang, Wen; Zeng, Qing-Ru; Zhou, Xi-Hong

2014-03-01

Through the simulation research, the effects of application of thiourea and urea on pH and availability of metal ions in acid red soil were studied, and the results showed that after applying urea, the soil pH increased in the first experimental stage and then reduced gradually to a low level, however, decreased trends of soil pH values were inhibited by the application of thiourea, especially when the concentration of thiourea reached to 5.0 mmol x kg(-1) dry soil, the soil pH was stable at high level, which exceeded to 6.0. It proved that the application of thiourea could inhibit the soil acidification due to urea application. After applying urea with different concentrations of thiourea, the available contents of Zn and Al decreased with the increasing concentration of thiourea, nevertheless, when the concentration of thiourea reached to 5.0 mmol x kg(-1), the available content of Mn was stable at high level which was over 110 mg x kg(-1). In addition, the results showed a highly significant negative correlation between the soil pH and the available content of Cu, Zn and Al, but for Mn, no discipline was found between the soil pH and the availability after applying thiourea. Moreover, the soil pH became higher after applying urea with thiourea compared to add urea only, which led to the decreasing of available content of Al, and it was benefited for the control of the phytotoxic effect of Al. The available content of Mn in the soil not only depended on soil pH but also the content of thiourea due to its redox and complexing reaction with Mn.

Plasma chemistry in booted eagle (Hieraaetus pennatus) during breeding season.

PubMed

Casado, Eva; Balbontin, Javier; Ferrer, Miguel

2002-02-01

Most studies that have examined raptor plasma chemistry have been conducted on birds living in captivity. In this study, we describe typical plasma chemistry values indicators of body condition in free-living Booted Eagles, Hieraaetus pennatus, from Doñana National Park (Spain). Values are compared with those of other raptors. Mean concentrations of creatinine, uric acid and urea were lower in adults than in nestlings, while glucose, DAT and AAT were lower in nestlings than in adults. Interactions of age/sex affected plasma mean levels of creatine kinase, glucose, AAT, uric acid and urea. Adult females showed significantly lower levels of creatine kinase, uric acid and urea than adult males and nestlings. Adult males had significantly higher levels of AAT than the other groups. The lowest levels of glucose and the highest levels of uric acid were found in nestling females. We think the differences in blood parameters can be explained by differences in size of species, of individuals (because of both body condition and sexual dimorphism) and diet.

A role for PPARα in the regulation of arginine metabolism and nitric oxide synthesis.

PubMed

Guelzim, Najoua; Mariotti, François; Martin, Pascal G P; Lasserre, Frédéric; Pineau, Thierry; Hermier, Dominique

2011-10-01

The pleiotropic effects of PPARα may include the regulation of amino acid metabolism. Nitric oxide (NO) is a key player in vascular homeostasis. NO synthesis may be jeopardized by a differential channeling of arginine toward urea (via arginase) versus NO (via NO synthase, NOS). This was studied in wild-type (WT) and PPARα-null (KO) mice fed diets containing either saturated fatty acids (COCO diet) or 18:3 n-3 (LIN diet). Metabolic markers of arginine metabolism were assayed in urine and plasma. mRNA levels of arginases and NOS were determined in liver. Whole-body NO synthesis and the conversion of systemic arginine into urea were assessed by using (15)N(2)-guanido-arginine and measuring urinary (15)NO(3) and [(15)N]-urea. PPARα deficiency resulted in a markedly lower whole-body NO synthesis, whereas the conversion of systemic arginine into urea remained unaffected. PPARα deficiency also increased plasma arginine and decreased citrulline concentration in plasma. These changes could not be ascribed to a direct effect on hepatic target genes, since NOS mRNA levels were unaffected, and arginase mRNA levels decreased in KO mice. Despite the low level in the diet, the nature of the fatty acids modulated some effects of PPARα deficiency, including plasma arginine and urea, which increased more in KO mice fed the LIN diet than in those fed the COCO diet. In conclusion, PPARα is largely involved in normal whole-body NO synthesis. This warrants further study on the potential of PPARα activation to maintain NO synthesis in the initiation of the metabolic syndrome.

Determining urea levels in exhaled breath condensate with minimal preparation steps and classic LC-MS.

PubMed

Pitiranggon, Masha; Perzanowski, Matthew S; Kinney, Patrick L; Xu, Dongqun; Chillrud, Steven N; Yan, Beizhan

2014-10-01

Exhaled breath condensate (EBC) provides a relatively easy, non-invasive method for measuring biomarkers of inflammation and oxidative stress in the airways. However, the levels of these biomarkers in EBC are influenced, not only by their levels in lung lining fluid but also by the volume of water vapor that also condenses during EBC collection. For this reason, the use of a biomarker of dilution has been recommended. Urea has been proposed and utilized as a promising dilution biomarker due to its even distribution throughout the body and relatively low volatility. Current EBC urea analytical methods either are not sensitive enough, necessitating large volumes of EBC, or are labor intensive, requiring a derivatization step or other pretreatment. We report here a straightforward and reliable LC-MS approach that we developed that does not require derivatization or large sample volume (∼36 µL). An Acclaim mixed-mode hydrophilic interaction chromatography column was selected because it can produce good peak symmetry and efficiently separate urea from other polar and nonpolar compounds. To achieve a high recovery rate, a slow and incomplete evaporation method was used followed by a solvent-phase exchange. Among EBC samples collected from 28 children, urea levels were found to be highly variable, with a relative standard deviation of 234%, suggesting high variability in dilution of the lung lining fluid component of EBC. The limit of detection was found to be 0.036 µg/mL. Published by Oxford University Press [2013]. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Mutant Potential Ubiquitination Sites in Dur3p Enhance the Urea and Ethyl Carbamate Reduction in a Model Rice Wine System.

PubMed

Zhang, Peng; Du, Guocheng; Zou, Huijun; Xie, Guangfa; Chen, Jian; Shi, Zhongping; Zhou, Jingwen

2017-03-01

Ubiquitination can significantly affect the endocytosis and degradation of plasma membrane proteins. Here, the ubiquitination of a Saccharomyces cerevisiae urea plasma membrane transporter (Dur3p) was altered. Two potential ubiquitination sites, lysine residues K556 and K571, of Dur3p were predicted and replaced by arginine, and the effects of these mutations on urea utilization and formation under different nitrogen conditions were investigated. Compared with Dur3p, the Dur3p K556R mutant showed a 20.1% decrease in ubiquitination level in yeast nitrogen base medium containing urea and glutamine. It also exhibited a >75.8% decrease in urea formation in yeast extract-peptone-dextrose medium and 41.3 and 55.4% decreases in urea and ethyl carbamate formation (a known carcinogen), respectively, in a model rice wine system. The results presented here show that the mutation of Dur3p ubiquitination sites could significantly affect urea utilization and formation. Modifying the ubiquitination of specific transporters might have promising applications in rationally engineering S. cerevisiae strains to efficiently use specific nitrogen sources.

Effect of frequency and amount of rumen-degradable intake protein supplementation on urea kinetics and microbial use of recycled urea in steers consuming low-quality forage.

PubMed

Wickersham, T A; Titgemeyer, E C; Cochran, R C; Wickersham, E E; Moore, E S

2008-11-01

We evaluated the effect of frequency and amount of rumen-degradable intake protein (DIP) on urea kinetics in steers consuming prairie hay. Five ruminally and duodenally fistulated steers (366 kg of BW) were used in a 5 x 5 Latin square and provided ad libitum access to low-quality prairie hay (4.7% CP). Casein was provided daily in amounts of 61 and 183 mg of N/kg of BW (61/d and 183/d) and every third day in amounts of 61, 183, and 549 mg of N/kg of BW per supplementation event (61/3d, 183/3d, and 549/3d). Periods were 18-d long with 9 d for adaptation and 9 d for collection. Steers were in metabolism crates for total collection of urine and feces. Jugular infusion of (15)N(15)N-urea followed by determination of urinary enrichment of (15)N(15)N-urea and (14)N(15)N-urea was used to determine urea kinetics. Treatment means were separated to evaluate the effects of increasing DIP supplementation and the effects of frequency at the low (61/d vs. 183/3d) and at the high (183/d vs. 549/3d) amounts of DIP provision. Forage OM and total digestible OM intakes were linearly (P < or = 0.05) increased by increasing DIP provision but were not affected by frequency of supplementation at either the low or high amounts. Production and gut entry of urea linearly (P < or = 0.006) increased with DIP provision and tended to be greater (P < or = 0.07) for 549/3d than 183/d but were not different between 61/d and 183/3d. Microbial N flow to the duodenum was linearly (P < 0.001) increased by increasing DIP provision. Additionally, 183/d resulted in greater (P = 0.05) microbial N flow than 549/3d. Incorporation of recycled urea-N into microbial N linearly (P = 0.04) increased with increasing DIP. Microbial incorporation of recycled urea-N was greater for 549/3d than 183/d, with 42 and 23% of microbial N coming from recycled urea-N, respectively. In contrast, there was no difference due to frequency in the incorporation of recycled urea-N by ruminal microbes at the low level of supplementation (i.e., 61/d vs. 183/3d). This study demonstrates that urea recycling plays a substantial role in the N supply to the rumen and to the animal, particularly in steers supplemented infrequently with high levels of protein.

Sirt3 promotes the urea cycle and fatty acid oxidation during dietary restriction

PubMed Central

Hallows, William C.; Yu, Wei; Smith, Brian C.; Devries, Mark K.; Ellinger, James J.; Someya, Shinichi; Shortreed, Michael R.; Prolla, Tomas; Markley, John L.; Smith, Lloyd M.; Zhao, Shimin; Guan, Kun-Liang; Denu, John M.

2011-01-01

Summary Emerging evidence suggests that protein acetylation is a broad-ranging regulatory mechanism. Here we utilize acetyl-peptide arrays and metabolomic analyses to identify substrates of mitochondrial deacetylase Sirt3. We identified ornithine transcarbamoylase (OTC) from the urea cycle, and enzymes involved in β-oxidation. Metabolomic analyses of fasted mice lacking Sirt3 (sirt3−/−) revealed alterations in β-oxidation and the urea cycle. Biochemical analysis demonstrated that Sirt3 directly deacetylates OTC and stimulates its activity. Mice under caloric restriction (CR) increased Sirt3 protein levels, leading to deacetylation and stimulation of OTC activity. In contrast, sirt3−/− mice failed to deacetylate OTC in response to CR. Inability to stimulate OTC under CR led to a failure to reduce orotic acid levels, a known outcome of OTC deficiency. Thus, Sirt3 directly regulates OTC activity and promotes the urea cycle during CR, and the results suggest that under low energy input, Sirt3 modulates mitochondria by promoting amino-acid catabolism and β-oxidation. PMID:21255725

The prevalence and pathogenesis of naturally-occurring Haemonchus longistipes infection in Sudanese camels.

PubMed

Arzoun, I H; Hussein, H S; Hussein, M F

1984-04-01

Camel haemonchosis is prevalent in the Sudan, especially during the rainy season, with a decrease in prevalence in the dry season possibly due to delayed maturation of the worms. The naturally occurring disease in Sudanese camels is characterized by emaciation, anaemia, oedema of the lower parts of the limbs, eosinophilia, hypoproteinaemia, hypoalbuminaemia, hyperglobulinaemia and eosinophilia, as well as elevated blood urea concentrations.

Tubulointerstitial nephritis and uveitis syndrome associated with hyperthyroidism.

PubMed

Ebihara, Itaru; Hirayama, Kouichi; Usui, Joichi; Seki, Masanori; Higuchi, Fujiko; Oteki, Takaaki; Kobayashi, Masaki; Yamagata, Kunihiro

2006-09-01

We report a 17-year-old male patient with tubulointerstitial nephritis and uveitis (TINU) associated with hyperthyroidism. He presented with a 2-month history of fatigue, loss of appetite, low-grade fever, and a 12-kg weight loss when he was admitted to our hospital. He had iritis, which was complicated by fibrin in the anterior chamber, diagnosed by slit-lamp examination. On laboratory examinations, deteriorated renal function (blood urea nitrogen level was 25.9 mg/dl and creatinine level was 2.82 mg/dl) and elevated urinary levels of N-acetyl-beta-D-glucosaminidase (33.1 U/l) and beta2-microglobulin (78,600 microg/l) were observed. Serum thyroid-stimulating hormone (TSH) was undetectable, at less than 0.01 microIU/ml, and free triiodothyronine and free thyroxine were elevated, up to 5.23 pg/ml and 2.85 ng/dl, respectively. The titers of antithyroglobulin and antithyroid microsomal and TSH-receptor antibodies were not elevated. Abdominal and thyroidal ultrasonography showed evident bilateral enlargement of the kidneys and diffuse enlargement of the thyroid gland. Iodine-123 scintigraphy showed low uptake in the thyroid gland. The biopsied renal specimen showed mild edema and severe diffuse infiltration of mononuclear cells and few eosinophils in the interstitium, without any glomerular or vascular abnormalities. Based on the clinical features and pathological findings, a diagnosis of TINU syndrome with associated hyperthyroidism was made. Treatment was started with 30 mg/day of prednisolone. The iritis disappeared, and the patient's clinical status improved remarkably. This case suggests the possibility of thyroid dysfunction in some patients with TINU syndrome, and we believe thyroid function should be measured in all TINU patients. Moreover, histopathological diagnosis of the thyroid glands before treatment is necessary for TINU patients with thyroid dysfunction.

New insights into urea and glucose handling by the kidney, and the urine concentrating mechanism.

PubMed

Bankir, Lise; Yang, Baoxue

2012-06-01

The mechanism by which urine is concentrated in the mammalian kidney remains incompletely understood. Urea is the dominant urinary osmole in most mammals and may be concentrated a 100-fold above its plasma level in humans and even more in rodents. Several facilitated urea transporters have been cloned. The phenotypes of mice with deletion of the transporters expressed in the kidney have challenged two previously well-accepted paradigms regarding urea and sodium handling in the renal medulla but have provided no alternative explanation for the accumulation of solutes that occurs in the inner medulla. In this review, we present evidence supporting the existence of an active urea secretion in the pars recta of the proximal tubule and explain how it changes our views regarding intrarenal urea handling and UT-A2 function. The transporter responsible for this secretion could be SGLT1, a sodium-glucose cotransporter that also transports urea. Glucagon may have a role in the regulation of this secretion. Further, we describe a possible transfer of osmotic energy from the outer to the inner medulla via an intrarenal Cori cycle converting glucose to lactate and back. Finally, we propose that an active urea transporter, expressed in the urothelium, may continuously reclaim urea that diffuses out of the ureter and bladder. These hypotheses are all based on published findings. They may not all be confirmed later on, but we hope they will stimulate further research in new directions.

Exploring Early Stages of the Chemical Unfolding of Proteins at the Proteome Scale

PubMed Central

Candotti, Michela; Pérez, Alberto; Ferrer-Costa, Carles; Rueda, Manuel; Meyer, Tim; Gelpí, Josep Lluís; Orozco, Modesto

2013-01-01

After decades of using urea as denaturant, the kinetic role of this molecule in the unfolding process is still undefined: does urea actively induce protein unfolding or passively stabilize the unfolded state? By analyzing a set of 30 proteins (representative of all native folds) through extensive molecular dynamics simulations in denaturant (using a range of force-fields), we derived robust rules for urea unfolding that are valid at the proteome level. Irrespective of the protein fold, presence or absence of disulphide bridges, and secondary structure composition, urea concentrates in the first solvation shell of quasi-native proteins, but with a density lower than that of the fully unfolded state. The presence of urea does not alter the spontaneous vibration pattern of proteins. In fact, it reduces the magnitude of such vibrations, leading to a counterintuitive slow down of the atomic-motions that opposes unfolding. Urea stickiness and slow diffusion is, however, crucial for unfolding. Long residence urea molecules placed around the hydrophobic core are crucial to stabilize partially open structures generated by thermal fluctuations. Our simulations indicate that although urea does not favor the formation of partially open microstates, it is not a mere spectator of unfolding that simply displaces to the right of the folded←→unfolded equilibrium. On the contrary, urea actively favors unfolding: it selects and stabilizes partially unfolded microstates, slowly driving the protein conformational ensemble far from the native one and also from the conformations sampled during thermal unfolding. PMID:24348236

UREA/ammonium ion removal system for the orbiting frog otolith experiment. [ion exchange resins for water treatment during space missions

NASA Technical Reports Server (NTRS)

Schulz, J. R.; Anselmi, R. T.

1976-01-01

The feasibility of using free urease enzyme and ANGC-101 ion exchange resin to remove urea and ammonium ion for space system waste water applications was studied. Specifically examined is the prevention of urea and ammonia toxicity in a 30-day Orbiting Frog Otolith (OFO) flight experiment. It is shown that free urease enzyme used in conjunction with ANGC-101 ion-exchange resin and pH control can control urea and amonium ion concentration in unbuffered recirculating water. In addition, the resin does not adversely effect the bullfrogs by lowering the concentration of cations below critical minimum levels. Further investigations on bioburden control, frog waste excretion on an OFO diet, a trade-off analysis of methods of automating the urea/ammonium ion removal system and fabrication and test of a semiautomated breadboard were recommended as continuing efforts. Photographs of test equipment and test animals are shown.

Metabolomics analysis reveals elevation of 3-indoxyl sulfate in plasma and brain during chemically-induced acute kidney injury in mice: Investigation of nicotinic acid receptor agonists

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zgoda-Pols, Joanna R., E-mail: joanna.pols@merck.com; Chowdhury, Swapan; Wirth, Mark

2011-08-15

An investigative renal toxicity study using metabolomics was conducted with a potent nicotinic acid receptor (NAR) agonist, SCH 900424. Liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS) techniques were used to identify small molecule biomarkers of acute kidney injury (AKI) that could aid in a better mechanistic understanding of SCH 900424-induced AKI in mice. The metabolomics study revealed 3-indoxyl sulfate (3IS) as a more sensitive marker of SCH 900424-induced renal toxicity than creatinine or urea. An LC-MS assay for quantitative determination of 3IS in mouse matrices was also developed. Following treatment with SCH 900424, 3IS levels were markedly increasedmore » in murine plasma and brain, thereby potentially contributing to renal- and central nervous system (CNS)-related rapid onset of toxicities. Furthermore, significant decrease in urinary excretion of 3IS in those animals due to compromised renal function may be associated with the elevation of 3IS in plasma and brain. These data suggest that 3IS has a potential to be a marker of renal and CNS toxicities during chemically-induced AKI in mice. In addition, based on the metabolomic analysis other statistically significant plasma markers including p-cresol-sulfate and tryptophan catabolites (kynurenate, kynurenine, 3-indole-lactate) might be of toxicological importance but have not been studied in detail. This comprehensive approach that includes untargeted metabolomic and targeted bioanalytical sample analyses could be used to investigate toxicity of other compounds that pose preclinical or clinical development challenges in a pharmaceutical discovery and development. - Research Highlights: > Nicotinic acid receptor agonist, SCH 900424, caused acute kidney injury in mice. > MS-based metabolomics was conducted to identify potential small molecule markers of renal toxicity. > 3-indoxyl-sulfate was found to be as a more sensitive marker of renal toxicity than creatinine or urea. > 3-IS levels were increased not only in murine plasma but also in the brain. > 3-IS potentially contributes to renal-and CNS-related rapid onset of toxicities.« less

Arginase induction by sodium phenylbutyrate in mouse tissues and human cell lines.

PubMed

Kern, R M; Yang, Z; Kim, P S; Grody, W W; Iyer, R K; Cederbaum, S D

2007-01-01

Hyperargininemia is a urea cycle disorder caused by mutations in the gene for arginase I (AI) resulting in elevated blood arginine and ammonia levels. Sodium phenylacetate and a precursor, sodium phenylbutyrate (NaPB) have been used to lower ammonia, conjugating glutamine to produce phenylacetylglutamine which is excreted in urine. The elevated arginine levels induce the second arginase (AII) in patient kidney and kidney tissue culture. It has been shown that NaPB increases expression of some target genes and we tested its effect on arginase induction. Eight 9-week old male mice fed on chow containing 7.5 g NaPB/kg rodent chow and drank water with 10 g NaPB/L, and four control mice had a normal diet. After one week all mice were sacrificed. The arginase specific activities for control and NaPB mice, respectively, were 38.2 and 59.4 U/mg in liver, 0.33 and 0.42 U/mg in kidney, and 0.29 and 1.19 U/mg in brain. Immunoprecipitation of arginase in each tissue with AI and AII antibodies showed the activity induced by NaPB is mostly AI. AII may also be induced in kidney. AI accounts for the fourfold increased activity in brain. In some cell lines, NaPB increased arginase activity up to fivefold depending on dose (1-5 mM) and exposure time (2-5 days); control and NaPB activities, respectively, are: erythroleukemia, HEL, 0.06 and 0.31 U/mg, and K562, 0.46 and 1.74 U/mg; embryonic kidney, HEK293, 1.98 and 3.58 U/mg; breast adenocarcinoma, MDA-MB-468, 1.11 and 4.06 U/mg; and prostate adenocarcinoma, PC-3, 0.55 and 3.20 U/mg. In MDA-MB-468 and HEK most, but not all, of the induced activity is AI. These studies suggest that NaPB may induce AI when used to treat urea cycle disorders. It is relatively less useful in AI deficiency, although it could have some effect in those patients with missense mutations.

Differential expression of multiple glutamine synthetase genes in air-breathing magur catfish, Clarias magur and their induction under hyper-ammonia stress.

PubMed

Banerjee, Bodhisattwa; Koner, Debaprasad; Bhuyan, Gitalee; Saha, Nirmalendu

2018-06-01

The present study demonstrates the unique presence of three different gs genes (cmgs01, cmgs02, and cmgs03) in air-breathing ureogenic magur catfish (Clarias magur), which is otherwise reported to be encoded by a single gene in higher vertebrates. Of these three genes, two (cmgs01and cmgs03) were identified as 'liver' form, predominantly expressed in liver cells, and the third one as 'brain' form (cmgs02), expressed chiefly in brain cells. Molecular characterization studies have revealed conservation of homologous active site residues in all the three gs genes. In silico analysis, accompanied by GS enzyme assay and Western blot analysis of different GS isoforms in different subcellular fractions indicated the mitochondrial localization of cmGS01 and cmGS03 in liver and kidney cells and cytosolic localization of cmGS02 in brain cells. Further, exposure of magur catfish to high external ammonia (HEA; 25 mM NH 4 Cl) led to a significant induction of multiple gs genes as evidenced by higher expression of different gs mRNAs at variable levels in different tissues. The cmgs01 and cmgs03 mRNA levels elevated significantly in liver, kidney, muscle, and gills, whereas the cmgs02 mRNA level increased considerably in the brain after 14 days of exposure to HEA. These increases in mRNA levels were associated with a significant rise in cmGS01 and cmGS03 proteins in liver, kidney, muscle, and gills, and the cmGS02 protein in the brain after 14 days of exposure to HEA. Therefore, it can be concluded that the unique differential expression of three gs genes and their induction under high ammonia level probably helps in detoxification of ammonia to glutamine and further to urea via the ornithine-urea cycle in ureogenic as well as non-ureogenic tissues of these magur catfish. Copyright © 2017. Published by Elsevier B.V.

Determinants of urea nitrogen production in sepsis. Muscle catabolism, total parenteral nutrition, and hepatic clearance of amino acids.

PubMed

Pittiruti, M; Siegel, J H; Sganga, G; Coleman, B; Wiles, C E; Placko, R

1989-03-01

The major determinants of urea production were investigated in 26 patients with multiple trauma (300 studies). The body clearances (CLRs) of ten amino acids (AAs) were estimated as a ratio of muscle-released AAs plus total parenteral nutrition-infused AAs to their extracellular pool. While clinically septic trauma (ST) patients without multiple-organ failure syndrome (MOFS) had a higher level of urea nitrogen production (25.6 +/- 13.4 g of N per day) compared with nonseptic trauma (NST) patients (14 +/- 7.5 g of N per day) and with ST patients with MOFS (4.28 +/- 1.5 g of N per day), in all groups urea N production was found to be a function of muscle protein degradation (catabolism), total parenteral nutrition-administered AAs, and the ratio between leucine CLR and tyrosine CLR (L/T) (r2 = .82, P less than .0001). Since tyrosine is cleared almost exclusively by the liver, the L/T ratio may be regarded as an index of hepatic function. The significant differences between urea N production in ST and NST patients lay in an increased positive dependence on muscle catabolism and increased negative correlation with L/T in the ST group. At any L/T ratio, urea N production was increased in ST patients over NST patients, but in ST patients with MOFS, it fell to or below levels of NST patients. These data show that the ST process is associated with enhancement of ureagenesis, due to increased hepatic CLR of both exogenous and endogenous AAs. In sepsis with MOFS, a marked inhibition of urea synthesis occurs, partially explained by a decreased hepatic CLR of non-branched-chain AAs.

ELEVATED PHENYLACETIC ACID LEVELS DO NOT CORRELATE WITH ADVERSE EVENTS IN PATIENTS WITH UREA CYCLE DISORDERS OR HEPATIC ENCEPHALOPATHY AND CAN BE PREDICTED BASED ON THE PLASMA PAA TO PAGN RATIO

PubMed Central

Mokhtarani, M.; Diaz, G.A.; Rhead, W.; Berry, S.A.; Lichter-Konecki, U.; Feigenbaum, A.; Schulze, A.; Longo, N.; Bartley, J.; Berquist, W.; Gallagher, R.; Smith, W.; McCandless, S.E.; Harding, C.; Rockey, D.C.; Vierling, J.M.; Mantry, P.; Ghabril, M.; Brown, R.S.; Dickinson, K.; Moors, T.; Norris, C.; Coakley, D.; Milikien, D.A.; Nagamani, SC; LeMons, C.; Lee, B.; Scharschmidt, B.F.

2014-01-01

Background Phenylacetic acid (PAA) is the active moiety in sodium phenylbutyrate (NaPBA) and glycerol phenylbutyrate (GPB, HPN-100), both are approved for treatment of urea cycle disorders (UCDs) - rare genetic disorders characterized by hyperammonemia. PAA is conjugated with glutamine in the liver to form phenylacetyleglutamine (PAGN), which is excreted in urine. PAA plasma levels ≥500 μg/dL have been reported to be associated with reversible neurological adverse events (AEs) in cancer patients receiving PAA intravenously. Therefore, we have investigated the relationship between PAA levels and neurological AEs in patients treated with these PAA pro-drugs as well as approaches to identifying patients most likely to experience high PAA levels. Methods The relationship between nervous system AEs, PAA levels and the ratio of plasma PAA to PAGN were examined in 4683 blood samples taken serially from: [1] healthy adults [2], UCD patients ≥2 months of age, and [3] patients with cirrhosis and hepatic encephalopathy (HE). The plasma ratio of PAA to PAGN was analyzed with respect to its utility in identifying patients at risk of high PAA values. Results Only 0.2% (11) of 4683 samples exceeded 500 ug/ml. There was no relationship between neurological AEs and PAA levels in UCD or HE patients, but transient AEs including headache and nausea that correlated with PAA levels were observed in healthy adults. Irrespective of population, a curvilinear relationship was observed between PAA levels and the plasma PAA:PAGN ratio, and a ratio > 2.5 (both in μg/mL) in a random blood draw identified patients at risk for PAA levels > 500 μg/ml. Conclusions The presence of a relationship between PAA levels and reversible AEs in healthy adults but not in UCD or HE patients may reflect intrinsic differences among the populations and/or metabolic adaptation with continued dosing. The plasma PAA:PAGN ratio is a functional measure of the rate of PAA metabolism and represents a useful dosing biomarker. PMID:24144944

Elevated phenylacetic acid levels do not correlate with adverse events in patients with urea cycle disorders or hepatic encephalopathy and can be predicted based on the plasma PAA to PAGN ratio.

PubMed

Mokhtarani, M; Diaz, G A; Rhead, W; Berry, S A; Lichter-Konecki, U; Feigenbaum, A; Schulze, A; Longo, N; Bartley, J; Berquist, W; Gallagher, R; Smith, W; McCandless, S E; Harding, C; Rockey, D C; Vierling, J M; Mantry, P; Ghabril, M; Brown, R S; Dickinson, K; Moors, T; Norris, C; Coakley, D; Milikien, D A; Nagamani, S C; Lemons, C; Lee, B; Scharschmidt, B F

2013-12-01

Phenylacetic acid (PAA) is the active moiety in sodium phenylbutyrate (NaPBA) and glycerol phenylbutyrate (GPB, HPN-100). Both are approved for treatment of urea cycle disorders (UCDs) - rare genetic disorders characterized by hyperammonemia. PAA is conjugated with glutamine in the liver to form phenylacetyleglutamine (PAGN), which is excreted in urine. PAA plasma levels ≥ 500 μg/dL have been reported to be associated with reversible neurological adverse events (AEs) in cancer patients receiving PAA intravenously. Therefore, we have investigated the relationship between PAA levels and neurological AEs in patients treated with these PAA pro-drugs as well as approaches to identifying patients most likely to experience high PAA levels. The relationship between nervous system AEs, PAA levels and the ratio of plasma PAA to PAGN were examined in 4683 blood samples taken serially from: [1] healthy adults [2], UCD patients of ≥ 2 months of age, and [3] patients with cirrhosis and hepatic encephalopathy (HE). The plasma ratio of PAA to PAGN was analyzed with respect to its utility in identifying patients at risk of high PAA values. Only 0.2% (11) of 4683 samples exceeded 500 μg/ml. There was no relationship between neurological AEs and PAA levels in UCD or HE patients, but transient AEs including headache and nausea that correlated with PAA levels were observed in healthy adults. Irrespective of population, a curvilinear relationship was observed between PAA levels and the plasma PAA:PAGN ratio, and a ratio>2.5 (both in μg/mL) in a random blood draw identified patients at risk for PAA levels>500 μg/ml. The presence of a relationship between PAA levels and reversible AEs in healthy adults but not in UCD or HE patients may reflect intrinsic differences among the populations and/or metabolic adaptation with continued dosing. The plasma PAA:PAGN ratio is a functional measure of the rate of PAA metabolism and represents a useful dosing biomarker. © 2013.

Protective effect of dexpanthenol on ischemia-reperfusion-induced renal injury in rats.

PubMed

Altintas, Ramazan; Parlakpinar, Hakan; Beytur, Ali; Vardi, Nigar; Polat, Alaadin; Sagir, Mustafa; Odabas, Gul Pelin

2012-01-01

This experimental study was designed to investigate protective and therapeutic effects of Dexpanthenol (Dxp), an alcoholic analogue of pantothenic acid, on kidney damage induced by ischemia-reperfusion (I/R) in rats. Forty rats were randomly divided into a control group and 4 I/R groups (1 h ischemia followed by 23 h reperfusion). Three I/R groups were treated by Dxp (500 mg/kg, i.p.) at 3 different time points (before ischemia, during ischemia and late reperfusion). The histopathological findings including apoptotic changes, and also tissue malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), blood urea nitrogen (BUN), serum creatinine (Cr) and albumin (Alb) levels were determined. Kidney tissue MDA levels were found to be significantly higher in the I/R group, whereas the values of GPX were lower when compared to the control group. The levels of SOD and CAT did not reach to statistical meaning level in I/R group. Dxp given during ischemia reduced the elevated MDA levels to the nearly control levels and this ameliorating effect was found as parallel to the result of GPX. Serum levels of BUN and Cr were significantly higher in I/R group. Dxp given during ischemia significantly reduced the elevated BUN and Cr levels when compared to I/R group. Renal I/R injury also induced extensive tubular necrosis, glomerular damage and apoptosis in the histological evaluation. Dxp ameliorated these histological damages in different amounts in all treatment groups. In this study the protective effects of Dxp against renal I/R injury has been evaluated for the first time. Copyright © 2012 S. Karger AG, Basel.

Sida rhomboidea.Roxb leaf extract ameliorates gentamicin induced nephrotoxicity and renal dysfunction in rats.

PubMed

Thounaojam, Menaka C; Jadeja, Ravirajsinh N; Devkar, Ranjitsinh V; Ramachandran, A V

2010-10-28

Sida rhomboidea.Roxb (SR) known as "Mahabala" in Ayurveda and marketed as "Shahadeyi" is used in ethnomedicine to treat ailments such as dysuria and urinary disorders. To evaluate nephroprotective potential of SR against gentamicin (GM) induced nephrotoxicity and renal dysfunction. Nephrotoxicity was induced in rats with GM (100 mg/kg bodyweight (i.p.) for 8 days) and were treated with SR extract (200 and 400 mg/kg bodyweight (p.o.) for 8 days) or 0.5% carboxymethyl cellulose (vehicle). Plasma and urine urea and creatinine, renal enzymatic and non-enzymatic antioxidants along with lipid peroxidation were evaluated in various experimental groups. GM treatment induced significant elevation (p<0.05) in plasma and urine urea, creatinine, renal lipid peroxidation along with significant decrement (p<0.05) in renal enzymatic and non-enzymatic antioxidants. SR treatment to GM treated rats (GM+SR) recorded significant decrement (p<0.05) in plasma and urine urea and creatinine, renal lipid peroxidation along with significant increment (p<0.05) in renal enzymatic and non-enzymatic antioxidants. SR leaf extract ameliorates GM induced nephrotoxicity and renal dysfunction and thus validates its ethnomedicinal use. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Sodium phenylbutyrate decreases plasma branched-chain amino acids in patients with urea cycle disorders.

PubMed

Burrage, Lindsay C; Jain, Mahim; Gandolfo, Laura; Lee, Brendan H; Nagamani, Sandesh C S

2014-01-01

Sodium phenylbutyrate (NaPBA) is a commonly used medication for the treatment of patients with urea cycle disorders (UCDs). Previous reports involving small numbers of patients with UCDs have shown that NaPBA treatment can result in lower plasma levels of the branched-chain amino acids (BCAA) but this has not been studied systematically. From a large cohort of patients (n=553) with UCDs enrolled in the Longitudinal Study of Urea Cycle Disorders, a collaborative multicenter study of the Urea Cycle Disorders Consortium, we evaluated whether treatment with NaPBA leads to a decrease in plasma BCAA levels. Our analysis shows that NaPBA use independently affects the plasma BCAA levels even after accounting for multiple confounding covariates. Moreover, NaPBA use increases the risk for BCAA deficiency. This effect of NaPBA seems specific to plasma BCAA levels, as levels of other essential amino acids are not altered by its use. Our study, in an unselected population of UCD subjects, is the largest to analyze the effects of NaPBA on BCAA metabolism and potentially has significant clinical implications. Our results indicate that plasma BCAA levels should to be monitored in patients treated with NaPBA since patients taking the medication are at increased risk for BCAA deficiency. On a broader scale, these findings could open avenues to explore NaPBA as a therapy in maple syrup urine disease and other common complex disorders with dysregulation of BCAA metabolism. Copyright © 2014 Elsevier Inc. All rights reserved.

Sodium Phenylbutyrate Decreases Plasma Branched-Chain Amino Acids in Patients with Urea Cycle Disorders

PubMed Central

Burrage, Lindsay C.; Jain, Mahim; Gandolfo, Laura; Lee, Brendan H.; Nagamani, Sandesh CS.

2014-01-01

Sodium phenylbutyrate (NaPBA) is a commonly used medication for the treatment of patients with urea cycle disorders (UCDs). Previous reports involving small numbers of patients with UCDs have shown that NaPBA treatment can result in lower plasma levels of the branched-chain amino acids (BCAA) but this has not been studied systematically. From a large cohort of patients (n=553) with UCDs enrolled in Longitudinal Study of Urea Cycle Disorders, a collaborative multicenter study of the Urea Cycle Disorders Consortium, we evaluated whether treatment with NaPBA leads to a decrease in plasma BCAA levels. Our analysis shows that NaPBA use independently affects the plasma BCAA levels even after accounting for multiple confounding covariates. Moreover, NaPBA use increases the risk for BCAA deficiency. This effect of NaPBA seems specific to plasma BCAA levels, as levels of other essential amino acids are not altered by its use. Our study, in an unselected population of UCD subjects, is the largest to analyze the effects of NaPBA on BCAA metabolism and potentially has significant clinical implications. Our results indicate that plasma BCAA levels should to be monitored in patients treated with NaPBA since patients taking the medication are at increased risk for BCAA deficiency. On a broader scale, they could open avenues to explore NaPBA as a therapy in maple syrup urine disease and other common complex disorders with dysregulation of BCAA metabolism. PMID:25042691

Exploring the molecular mechanism of trimethylamine-N-oxide's ability to counteract the protein denaturing effects of urea.

PubMed

Sarma, Rahul; Paul, Sandip

2013-05-09

Protein denaturation in highly concentrated urea solution is a well-known phenomenon. The counteracting effect of a naturally occurring osmolyte, trimethylamine-N-oxide (TMAO), against urea-conferred protein denaturation is also well-established. However, what is largely unknown is the mechanism by which TMAO counteracts this denaturation. To provide a molecular level understanding of how TMAO protects proteins in highly concentrated urea solution, we report here the structural, energetic, and dynamical properties of N-methylacetamide (NMA) solutions that also contain urea and/or TMAO. The solute NMA is of interest mainly because it contains the peptide linkage in addition to hydrophobic sites and represents the typical solvent-exposed state of proteins. Molecular dynamics computer simulation technique is employed in this study. Analysis of solvation characteristics reveals dehydration of NMA and reduction in hydrogen bond number between NMA oxygen and water upon addition of TMAO. The effect of TMAO on NMA-urea interaction is found to be insignificant. Because TMAO cannot donate its hydrogen to NMA oxygen, the total number of hydrogen bonds formed by NMA oxygen with solution species decreases in the presence of TMAO. In solution, TMAO is found to interact strongly with water and urea. Solvation of TMAO makes the water hydrogen bonding network relatively stronger and reduces relaxation of urea-water hydrogen bonds. Implications of these results for counteracting mechanism of TMAO are discussed.

Effects of encapsulated nitrate on growth performance, carcass characteristics, nitrate residues in tissues, and enteric methane emissions in beef steers: Finishing phase.

PubMed

Lee, C; Araujo, R C; Koenig, K M; Beauchemin, K A

2017-08-01

A finishing feedlot study was conducted with beef steers to determine effects of encapsulated nitrate (EN) on growth performance, carcass characteristics, methane production, and nitrate (NO) residues in tissues. The 132 crossbred steers were backgrounded in a feedlot for 91 d and transitioned for 28 days to the high-concentrate diets evaluated in the present study, maintaining the treatment and pen assignments designated at the start of the backgrounding period. The steers were initially assigned to 22 pens (6 animals per pen) in a randomized complete block design with BW (18 pens) and animals designated for methane measurement (4 pens) as blocking factors. Five animals in each pen designated for methane measurement (total of 20 animals) were monitored for methane emissions in respiratory chambers twice during the experiment. Pens received 3 dietary treatments (7 pens each): Control, a finishing diet supplemented with urea; 1.25% EN, control diet supplemented with 1.25% encapsulated NO in dietary DM that partially replaced urea; and 2.5% EN, control diet supplemented with 2.5% EN (DM basis) fully replacing urea. The final pen designated only for methane measurement received a fourth dietary treatment, 2.3% UEN, the control diet supplemented with unencapsulated NO (UEN) fully replacing urea. The cattle weighed 449 ± SD 32 kg at the start of the 150-d finishing period. The 2.5% EN diet decreased ( < 0.01) DMI compared with Control and 1.25% EN diets. Feeding EN tended to increase ( = 0.092) ADG compared with Control, and G:F was improved ( < 0.01) for EN compared with Control. No differences in methane production (g/d) and yield (g/kg DMI) were observed among treatments. Inclusion of EN in the diets increased ( ≤ 0.03) sorting in favor of large and medium particles and against small and fine particles. Plasma NO and NO concentrations were elevated ( < 0.01) with EN in a dose-response manner, but total blood methemoglobin levels for all treatments were low, below the detection limit. Feeding EN increased ( < 0.01) NO concentrations of samples from muscle, fat, liver, and kidney; NO concentrations of these tissues were similar between 1.25% EN and 2.3% UEN. In conclusion, inclusion of 2.5% EN in a finishing diet (DM basis; about 2% NO) did not cause NO toxicity or any health problems in the long term. In comparison with supplemental urea, feeding EN improved feed efficiency despite increases in sorting against dietary EN.

Successful use of alternate waste nitrogen agents and hemodialysis in a patient with hyperammonemic coma after heart-lung transplantation.

PubMed

Berry, G T; Bridges, N D; Nathanson, K L; Kaplan, P; Clancy, R R; Lichtenstein, G R; Spray, T L

1999-04-01

Lethal hyperammonemic coma has been reported in 2 adults after lung transplantation. It was associated with a massive elevation of brain glutamine levels, while plasma glutamine levels were normal or only slightly elevated. In liver tissue, glutamine synthetase activity was markedly reduced, and the histologic findings resembled those of Reye syndrome. The adequacy of therapy commonly used for inherited disorders of the urea cycle has not been adequately evaluated in patients with this form of secondary hyperammonemia. To determine whether hemodialysis, in conjunction with intravenous sodium phenylacetate, sodium benzoate, and arginine hydrochloride therapy, would be efficacious in a patient with hyperammonemic coma after solid-organ transplantation. Case report. A children's hospital. A 41-year-old woman with congenital heart disease developed a hyperammonemic coma with brain edema 19 days after undergoing a combined heart and lung transplantation. Ammonium was measured in plasma. Amino acids were quantitated in plasma and cerebrospinal fluid by column chromatography. The effectiveness of therapy was assessed by measuring plasma ammonium levels and intracranial pressure and performing sequential neurological examinations. The patient had the anomalous combination of increased cerebrospinal fluid and decreased plasma glutamine levels. To our knowledge, she is the first patient with this complication after solid-organ transplantation to survive after combined therapy with sodium phenylacetate, sodium benzoate, arginine hydrochloride, and hemodialysis. Complications of the acute coma included focal motor seizures, which were controlled with carbamazepine, and difficulty with short-term memory. The aggressive use of hemodialysis in conjunction with intravenous sodium phenylacetate, sodium benzoate, and arginine hydrochloride therapy may allow survival in patients after solid-organ transplantation. An acute acquired derangement in extra-central nervous system glutamine metabolism may play a role in the production of hyperammonemia in this illness that resembles Reye syndrome, and, as in other hyperammonemic disorders, the duration and degree of elevation of brain glutamine levels may be the important determining factors in responsiveness to therapy.

Urea enhances the photodynamic efficiency of methylene blue.

PubMed

Nuñez, Silvia C; Yoshimura, Tania M; Ribeiro, Martha S; Junqueira, Helena C; Maciel, Cleiton; Coutinho-Neto, Maurício D; Baptista, Maurício S

2015-09-01

Methylene blue (MB) is a well-known photosensitizer used mostly for antimicrobial photodynamic therapy (APDT). MB tends to aggregate, interfering negatively with its singlet oxygen generation, because MB aggregates lean towards electron transfer reactions, instead of energy transfer with oxygen. In order to avoid MB aggregation we tested the effect of urea, which destabilizes solute-solute interactions. The antimicrobial efficiency of MB (30 μM) either in water or in 2M aqueous urea solution was tested against a fungus (Candida albicans). Samples were kept in the dark and irradiation was performed with a light emitting diode (λ = 645 nm). Without urea, 9 min of irradiation was needed to achieve complete microbial eradication. In urea solution, complete eradication was obtained with 6 min illumination (light energy of 14.4 J). The higher efficiency of MB/urea solution was correlated with a smaller concentration of dimers, even in the presence of the microorganisms. Monomer to dimer concentration ratios were extracted from the absorption spectra of MB solutions measured as a function of MB concentration at different temperatures and at different concentrations of sodium chloride and urea. Dimerization equilibrium decreased by 3 and 6 times in 1 and 2M urea, respectively, and increased by a factor of 6 in 1M sodium chloride. The destabilization of aggregates by urea seems to be applied to other photosensitizers, since urea also destabilized aggregation of Meso-tetra(4-n-methyl-pyridyl)porphyrin, which is a positively charged porphyrin. We showed that urea destabilizes MB aggregates mainly by causing a decrease in the enthalpic gain of dimerization, which was exactly the opposite of the effect of sodium chloride. In order to understand this phenomenon at the molecular level, we computed the free energy for the dimer association process (ΔG(dimer)) in aqueous solution as well as its enthalpic component in aqueous and in aqueous/urea solutions by molecular dynamics simulations. In 2M-urea solution the atomistic picture revealed a preferential solvation of MB by urea compared with MB dimers while changes in ΔH(dimer) values demonstrated a clear shift favoring MB monomers. Therefore, MB monomers are more stable in urea solutions, which have significantly better photophysics and higher antimicrobial activity. This information can be of use for dental and medical professionals that are using MB based APDT protocols. Copyright © 2015 Elsevier B.V. All rights reserved.

Phosphate, urea and creatinine clearances: haemodialysis adequacy assessed by weekly monitoring.

PubMed

Debowska, Malgorzata; Wojcik-Zaluska, Alicja; Ksiazek, Andrzej; Zaluska, Wojciech; Waniewski, Jacek

2015-01-01

The specific distribution of phosphate and the control mechanisms for its plasma level makes phosphate kinetics during haemodialysis (HD) considerably different from those of urea and creatinine and makes the quantitative evaluation of adequacy of phosphate removal difficult. We propose the application of equivalent continuous clearance (ECC) as a phosphate adequacy parameter and compare it with ECC for creatinine and urea. Three consecutive dialysis sessions were evaluated for 25 patients on maintenance HD. Concentrations of phosphate, urea and creatinine in plasma were measured every 1h during the treatment and 45 min after, and every 30 min in dialysate. ECC was calculated using the removed solute mass assessed in dialysate and weekly solute profile in plasma. Similar calculations were performed also for the midweek dialysis session only. Different versions of the reference concentration for ECC were applied. ECC with peak average reference concentration was 5.4 ± 1.0 for phosphate, 7.0 ± 1.0 for urea and 4.7 ± 1.0 mL/min for creatinine. ECC for urea and creatinine were well correlated in contrast to the correlations of ECC for phosphate versus urea and creatinine. Midweek ECC were higher than weekly ECC, but they were well correlated for urea and creatinine, but only weakly for phosphate. HD adequacy monitoring for phosphate may be performed using ECC, but it is less predictable than similar indices for urea and creatinine. The values of ECC for phosphate are within the range expected for its molecular size compared with those for urea and creatinine. © The Author 2014. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Urea encapsulation in modified starch matrix for nutrients retention

NASA Astrophysics Data System (ADS)

Naz, Muhammad Yasin; Sulaiman, Shaharin Anwar; Ariff, Mohd. Hazwan Bin Mohd.; Ariwahjoedi, Bambang

2014-10-01

It has been estimated that 20-70% of the used urea goes to the environment via leaching, nitrification and volatilization which not only harms the environment but also reduces the urea efficiency. By coating the urea granules, the farmers can achieve high urea performance through controlling the excess release of nitrogen. Up until now, different materials have been tested for nutrients retention. However, most of them are either expensive or unfriendly to the environment. Being cheap and biodegradable materials, the starches may also be used to coat the urea fertilizer for controlling the nutrients release. However, the pure starches do not meet the standards set by many industrial processes due to their slow tacking and too low viscosities and should be modified for getting smooth, compact and mechanically stronger coatings. In these studies, the tapioca starch was modified by reacting it with urea and different masses of borax. The prepared solutions were used to coat the urea granules of 3.45 mm average diameter. Different volumes (1, 1.5 and 2 mL) of each solution were used to coat 30 g of urea fluidized above the minimum level of fluidization. It was noticed that the coating thickness, percent coating, dissolution rate and percent release follow an increasing trend with an increase of solution volume; however, some random results were obtained while investigating the solution volume effects on the percent release. It was seen that the nutrients percent release over time increases with an increase in solution volume from 1 to 1.5 mL and thereafter reaches to a steady state. It confirms that the 1.5 mL of solution for 30 g urea samples will give the optimized coating results.

Microscopic significance of hydrophobic residues in the protein-stabilizing effect of trimethylamine N-oxide (TMAO).

PubMed

Yang, Yanmei; Mu, Yuguang; Li, Weifeng

2016-08-10

Although it is widely known that trimethylamine N-oxide (TMAO) stabilizes the native structure of proteins, the underlying mechanism of its action is poorly documented. To obtain an in-depth understanding of this important osmolyte molecule, we conducted large-scale molecular dynamic simulations of model proteins, namely, wild-type villin headpiece protein HP35 and its doubly norleucine-substituent mutant (Lys24/29Nle) HP35NN in pure urea and urea + TMAO mixed solutions for direct comparison. From extensive sampling, the protective capability of TMAO was well captured in the simulations, where HP35NN demonstrated a significantly more stable native structure than HP35 in the presence of TMAO, whereas in pure urea solution, the former denatured in a shorter time. These findings highlight the importance of the two norleucine residues that regulates the interactions of proteins with urea and TMAO. By accessing the hydration and conformational dynamics of both proteins, we were able to directly probe how TMAO compensates the denaturing effect of urea at the atomic level. The accumulation of urea around hydrophobic residues is clearly suppressed, which indicates that the van der Waals interactions between urea and proteins are weakened by TMAO. As a consequence, the hydrophobic core of protein is preferentially protected by TMAO against urea attack. Although the hydrogen bonds (H-bonds) between proteins and urea are suppressed by TMAO, this plays a very minor role than expected in the enhanced protein stability. In addition, TMAO was found to be always excluded from the protein surface and incapable of forming H-bonds with proteins. Thus, the present study provides solid evidence to support the indirect mechanism of TMAO counteracting the denaturing effects of urea.

Effect of irrigation and timing and type of nitrogen application on the biochemical composition of Vitis vinifera L. cv. Chardonnay and Syrah grapeberries.

PubMed

Canoura, Carolina; Kelly, Mary T; Ojeda, Hernan

2018-02-15

This study reports the effect of different doses of nitrogen applied to soil and/or leaves of Syrah and Chardonnay grapevines in the Languedoc-Roussillon (France) over two years. In 2011, nitrogen treatment involved both foliar urea sprayings and soil application at two different levels, with two controls - irrigated without nitrogen and no irrigation nor nitrogen. In 2012, the same grapevines received either soil or foliar nitrogen using the same controls. Results showed that foliar application increased the amino acid content to a greater extent than soil application, but that a combination of both was the most effective. For the first time, significantly elevated proline levels in response to drought were demonstrated for the grapevine. Increased contents of aromatic compounds and glycosylated precursors closely mirrored the applied nitrogen dose. Wines produced from N-fertilized Syrah grapes in 2011 showed a statistically significant effect of irrigation and fertilization on positive sensorial perception. Copyright © 2017 Elsevier Ltd. All rights reserved.

Lycium chinense leaves extract ameliorates diabetic nephropathy by suppressing hyperglycemia mediated renal oxidative stress and inflammation.

PubMed

Olatunji, Opeyemi Joshua; Chen, Hongxia; Zhou, Yifeng

2018-06-01

Diabetic nephropathy is one of the most serious and most frequently encountered diabetic complication, accounting for the highest cause of end-stage renal disease. This present study was aimed at exploring the protective/attenuative effect of Lycium chinense leaf extract (MELC) on streptozotocin induced diabetic nephropathy in experimental Sprague Dawley rats. The oral administration of diabetic rats with MELC markedly ameliorated renal dysfunction as observed in the significant reduction in the serum levels of creatinine, blood urea nitrogen (BUN), albumin and TGF-β1 as compared to the untreated diabetic control rats. In addition, the elevated levels of renal oxidative stress markers and pro-inflammatory parameters (GSH, SOD, CAT, MDA, TNF-α, IL-6 and IL-1β) were significantly reduced in MELC treated diabetic rats. The results obtained in this study suggests that L. chinense leaf might have the potential as possible pharmacological agent against diabetic nephropathy by suppressing renal oxidative stress and inflammation. Copyright © 2018. Published by Elsevier Masson SAS.

Antihyperglycaemic and organic protective effects on pancreas, liver and kidney by polysaccharides from Hericium erinaceus SG-02 in streptozotocin-induced diabetic mice.

PubMed

Zhang, Chen; Li, Juan; Hu, Chunlong; Wang, Jing; Zhang, Jianjun; Ren, Zhenzhen; Song, Xinling; Jia, Le

2017-09-07

The present work was designed to investigate the antihyperglycaemic and protective effects of two Hericium erinaceus intracellular polysaccharide (HIPS) purified fractions (HIPS1 and HIPS2) from mycelia of H. erinaceus SG-02 on pancreas, liver and kidney in streptozotocin (STZ)-induced diabetic mice. The supplementation of HIPS1 and HIPS2 significantly decreased the blood glucose (GLU) levels; suppressed the abnormal elevations of alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea nitrogen (BUN) and creatinine (CRE) levels in serum; improved the antioxidant enzymatic (superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT)) activities; and attenuated the pathological damage to these organs. The HIPS1 showed superior effects in antihyperglycaemia and organic protection than HIPS2 possible owing to the abundant functional groups (-NH 2 , -COOH and S=O) in HIPS1, indicating that H. erinaceus SG-02 could be used as a functional food and natural drug for the prevention of diabetes and its complications.

Crocin attenuates hemorrhagic shock-induced oxidative stress and organ injuries in rats.

PubMed

Yang, Long; Dong, Xiujuan

2017-06-01

We aimed to evaluate the effect of natural antioxidant crocin in alleviating hemorrhagic shock (HS)-induced organ damages. HS rats were treated with crocin during resuscitation. Mortality at 12h and 24h post resuscitation was documented. HS and resuscitation induced organ injuries, as characterized by elevated wet/dry ratio, quantitative assessment ratio, blood urea nitrogen, creatinine, aspartate aminotransferase and alanine aminotransferase, whereas rats received crocin treatment demonstrated improvements in all the above characteristics. This protective effect coincided with reduced malondialdehyde and increased glutathione in both serum and lung tissues, indicating attenuated oxidative stress in crocin-treated rats. Myeloperoxide levels in lung, kidney and liver were also reduced. Crocin can potentially be used to protect organs from HS-induced damages during resuscitation due to its anti-oxidative role. Copyright © 2017 Elsevier B.V. All rights reserved.

Long-term outcomes in a family with nephrogenic syndrome of inappropriate antidiuresis.

PubMed

Cho, Yoon Hi; Gitelman, Stephen; Rosenthal, Stephen; Ambler, Geoffrey

2009-01-01

We report a familial case of the nephrogenic syndrome of inappropriate antidiuresis (NSIAD), including 30-year followup data on two patients. The proband and one maternal uncle presented in their infancy with severe recurrent hyponatremia, and clinical pictures consistent with the syndrome of inappropriate antidiuretic hormone (SIADH) in the absence of an elevated ADH level. They were both confirmed to be hemizygous for the R137C mutation on the V2R gene (AVPR2), the same locus of the gain of function mutation demonstrated in the original reports of this condition. The proband's mother was identified as an asymptomatic carrier of this X-linked condition. Our case describes a favourable long-term outcome for NSIAD, in particular, successful treatment with oral urea during the infancy period, and with self-regulated precautions on fluid intake into adult life.

Protective Role of Spirulina platensis against Acute Deltamethrin-Induced Toxicity in Rats

PubMed Central

Abdel-Daim, Mohamed M.; Abuzead, Said M. M.; Halawa, Safaa M.

2013-01-01

Deltamethrin is a broad-spectrum synthetic pyrethroid insecticide and acaricide widely used for agricultural and veterinary purposes. However, its human and animal exposure leads to hepatonephrotoxicity. Therefore, the present study was undertaken to examine the hepatonephroprotective and antioxidant potential of Spirulina platensis against deltamethrin toxicity in male Wistar albino rats. Deltamethrin treated animals revealed a significant increase in serum biochemical parameters as well as hepatic and renal lipid peroxidation but caused an inhibition in antioxidant biomarkers. Spirulina normalized the elevated serum levels of AST, ALT, APL, uric acid, urea and creatinine. Furthermore, it reduced deltamethrin-induced lipid peroxidation and oxidative stress in a dose dependent manner. Therefore, it could be concluded that spirulina administration able to minimize the toxic effects of deltamethrin by its free radical-scavenging and potent antioxidant activity. PMID:24039839

Nitrification of archaeal ammonia oxidizers in acid soils is supported by hydrolysis of urea

PubMed Central

Lu, Lu; Han, Wenyan; Zhang, Jinbo; Wu, Yucheng; Wang, Baozhan; Lin, Xiangui; Zhu, Jianguo; Cai, Zucong; Jia, Zhongjun

2012-01-01

The hydrolysis of urea as a source of ammonia has been proposed as a mechanism for the nitrification of ammonia-oxidizing bacteria (AOB) in acidic soil. The growth of Nitrososphaera viennensis on urea suggests that the ureolysis of ammonia-oxidizing archaea (AOA) might occur in natural environments. In this study, 15N isotope tracing indicates that ammonia oxidation occurred upon the addition of urea at a concentration similar to the in situ ammonium content of tea orchard soil (pH 3.75) and forest soil (pH 5.4) and was inhibited by acetylene. Nitrification activity was significantly stimulated by urea fertilization and coupled well with abundance changes in archaeal amoA genes in acidic soils. Pyrosequencing of 16S rRNA genes at whole microbial community level demonstrates the active growth of AOA in urea-amended soils. Molecular fingerprinting further shows that changes in denaturing gradient gel electrophoresis fingerprint patterns of archaeal amoA genes are paralleled by nitrification activity changes. However, bacterial amoA and 16S rRNA genes of AOB were not detected. The results strongly suggest that archaeal ammonia oxidation is supported by hydrolysis of urea and that AOA, from the marine Group 1.1a-associated lineage, dominate nitrification in two acidic soils tested. PMID:22592820

Nitrification of archaeal ammonia oxidizers in acid soils is supported by hydrolysis of urea.

PubMed

Lu, Lu; Han, Wenyan; Zhang, Jinbo; Wu, Yucheng; Wang, Baozhan; Lin, Xiangui; Zhu, Jianguo; Cai, Zucong; Jia, Zhongjun

2012-10-01

The hydrolysis of urea as a source of ammonia has been proposed as a mechanism for the nitrification of ammonia-oxidizing bacteria (AOB) in acidic soil. The growth of Nitrososphaera viennensis on urea suggests that the ureolysis of ammonia-oxidizing archaea (AOA) might occur in natural environments. In this study, (15)N isotope tracing indicates that ammonia oxidation occurred upon the addition of urea at a concentration similar to the in situ ammonium content of tea orchard soil (pH 3.75) and forest soil (pH 5.4) and was inhibited by acetylene. Nitrification activity was significantly stimulated by urea fertilization and coupled well with abundance changes in archaeal amoA genes in acidic soils. Pyrosequencing of 16S rRNA genes at whole microbial community level demonstrates the active growth of AOA in urea-amended soils. Molecular fingerprinting further shows that changes in denaturing gradient gel electrophoresis fingerprint patterns of archaeal amoA genes are paralleled by nitrification activity changes. However, bacterial amoA and 16S rRNA genes of AOB were not detected. The results strongly suggest that archaeal ammonia oxidation is supported by hydrolysis of urea and that AOA, from the marine Group 1.1a-associated lineage, dominate nitrification in two acidic soils tested.

Polymer Coated Urea in Turfgrass Maintains Vigor and Mitigates Nitrogen's Environmental Impacts

PubMed Central

LeMonte, Joshua J.; Jolley, Von D.; Summerhays, Jeffrey S.; Terry, Richard E.; Hopkins, Bryan G.

2016-01-01

Polymer coated urea (PCU) is a N fertilizer which, when added to moist soil, uses temperature-controlled diffusion to regulate N release in matching plant demand and mitigate environmental losses. Uncoated urea and PCU were compared for their effects on gaseous (N2O and NH3) and aqueous (NO3-) N environmental losses in cool season turfgrass over the entire PCU N-release period. Field studies were conducted on established turfgrass sites with mixtures of Kentucky bluegrass (Poa pratensis L.) and perennial ryegrass (Lolium perenne L.) in sand and loam soils. Each study compared 0 kg N ha-1 (control) to 200 kg N ha-1 applied as either urea or PCU (Duration 45CR®). Application of urea resulted in 127–476% more evolution of measured N2O into the atmosphere, whereas PCU was similar to background emission levels from the control. Compared to urea, PCU reduced NH3 emissions by 41–49% and N2O emissions by 45–73%, while improving growth and verdure compared to the control. Differences in leachate NO3- among urea, PCU and control were inconclusive. This improvement in N management to ameliorate atmospheric losses of N using PCU will contribute to conserving natural resources and mitigating environmental impacts of N fertilization in turfgrass. PMID:26764908

Fatal ammonia toxicity in an adult due to an undiagnosed urea cycle defect: under-recognition of ornithine transcarbamylase deficiency.

PubMed

Thurlow, Vanessa R; Asafu-Adjaye, Michelle; Agalou, Stamatina; Rahman, Yusof

2010-05-01

There is a lack of awareness of acutely presenting inborn errors of metabolism in adults, of which the X-linked urea cycle defect ornithine transcarbamylase (OTC) deficiency is an example, many comparatively mild mutations having been identified. In male hemizygotes clinical manifestations and age at presentation vary and depend on the mutation. In female heterozygotes the clinical spectrum depends on the extent to which the abnormal gene is expressed. Milder versions of the defect may not cause clear clinical symptoms and may remain unrecognized until the person is subjected to an unusually high nitrogen load when they develop severe hyperammonaemia. During acute episodes liver enzymes may be normal or only slightly elevated and occasionally accompanied by coagulopathy, but the key finding is hyperammonaemia. Boys with these milder forms may exhibit abnormal behaviour and be diagnosed with attention deficit hyperactivity disorder. This case illustrates how late presentation of OTC deficiency in a non-specialist centre can be difficult to differentiate from drug abuse, psychiatric illness or encephalopathy. Failure to measure blood ammonia in adults with unexplained key symptoms - particularly prolonged vomiting without diarrhoea and altered mental state/hallucinations, or to recognize the significance of elevated blood ammonia without evidence of liver decompensation can lead to delayed or missed diagnosis.

Role of rumen butyrate in regulation of nitrogen utilization and urea nitrogen kinetics in growing sheep.

PubMed

Agarwal, U; Hu, Q; Baldwin, R L; Bequette, B J

2015-05-01

Butyrate, a major rumen VFA, has been indirectly linked to enhancement of urea recycling on the basis of increased expression of urea transporter in the rumen epithelia of steers fed a rumen butyrate-enhancing diet. Two studies were conducted to quantify the effect of elevated rumen butyrate concentrations on N balance, urea kinetics and rumen epithelial proliferation. Wether sheep (n= 4), fitted with a rumen cannula, were fed a pelleted ration (∼165 g CP/kg DM, 10.3 MJ ME/kg DM) at 1.8 × ME requirement. In Exp. 1, sheep were infused intraruminally with either an electrolyte buffer solution (Con-Buf) or butyrate dissolved in the buffer solution (But-Buf) during 8-d periods in a balanced crossover design. In Exp. 2, sheep were infused intraruminally with either sodium acetate (Na-Ac) or sodium butyrate (Na-But) for 9 d. All solutions were adjusted to pH 6.8 and 8.0 in Exp. 1 and 2, respectively, and VFA were infused at 10% of ME intake. [15N2] urea was continuously infused intravenously for the last 5 d of each period, and total urine and feces were collected. In Exp. 1, 2H5-phenylalanine was continuously infused intravenously over the last 12 h, after which a biopsy from the rumen papillae was taken for measurement of fractional protein synthesis rate (FSR). Butyrate infusion treatments increased (P = 0.1 in Exp. 1; P < 0.05 in Exp. 2) the proportion of rumen butyrate, and acetate infusion increased (P < 0.05) rumen acetate. All animals were in positive N balance (4.2 g N/d in Exp. 1; 7.0 g N/d in Exp. 2), but no difference in N retention was observed between treatments. In Exp. 2, urea entry (synthesis) rate was reduced ( < 0.05) by Na-But compared with the Na-Ac control. In Exp. 1, although But-Buf infusion increased the FSR of rumen papillae (35.3% ± 1.08%/d vs. 28.7% ± 1.08%/d; P < 0.05), urea kinetics were not altered by But-Buf compared with Con-Buf. These studies are the first to directly assess the role of butyrate in urea recycling and its effects on rumen papillae protein turnover in growing lambs. Under the feeding conditions used and the rate of continuous butyrate infusion into the rumen in the present studies, butyrate does not affect overall N retention in growing sheep. However, butyrate may play a role in the redistribution of urea N fluxes in the overall scheme of N metabolism.

Antioxidant activity and protective effect of bee bread (honey and pollen) in aluminum-induced anemia, elevation of inflammatory makers and hepato-renal toxicity.

PubMed

Bakour, Meryem; Al-Waili, Noori S; El Menyiy, Nawal; Imtara, Hamada; Figuira, Anna Cristina; Al-Waili, Thia; Lyoussi, Badiaa

2017-12-01

Aluminum toxicity might be related to oxidative stress, and the antioxidant activity and protective effect of bee bread, which contains pollen, honey and bees' enzymes, on aluminum induced blood and hepato-renal toxicity was investigated in rats. Chemical analysis and antioxidant capacity of bee bread were conducted. The animal experiment in rats included; group 1: received distilled water (10 ml/kg b.wt), group 2: received aluminum chloride (662.2 mg/kg b.wt), group 3: received aluminum chloride (662.2 mg/kg b.wt) and ethanolic extract of the bee bread (500 mg/kg b.wt), and group 4: received aluminum chloride (662.2 mg/kg b.wt) and ethanolic extract of the bee bread (750 mg/kg b.wt). Doses were given once daily via a gavage. C-reactive protein, transaminases, urea, creatinine, creatinine clearance, sodium and potassium and urine sodium and potassium were determined on day 28 of the experiment. Bee bread contained protein, fat, fiber, ash, carbohydrate, phenol and flavonoids and it exhibited antioxidant activity. Aluminum caused a significant elevation of blood urea, transaminase, C-reactive protein and monocyte count and significantly decreased hemoglobin. These changes were significantly ameliorated by the use of bee bread. Bee bread has an antioxidant property, and exhibited a protective effect on aluminum induced blood and hepato-renal toxicity and elevation of inflammatory markers C-reactive protein, leukocyte and monocyte counts.

Microfluidic optoelectronic sensor for salivary diagnostics of stomach cancer.

PubMed

Zilberman, Yael; Sonkusale, Sameer R

2015-05-15

We present a microfluidic optoelectronic sensor for saliva diagnostics with a potential application for non-invasive early diagnosis of stomach cancer. Stomach cancer is the second most common cause of cancer-related deaths in the world. The primary identified cause is infection by a gram-negative bacterium Helicobacter pylori. These bacteria secrete the enzyme urease that converts urea into carbon dioxide (CO2) and ammonia (NH3), leading to their elevated levels in breath and body fluids. The proposed optoelectronic sensor will detect clinically relevant levels of CO2 and NH3 in saliva that can potentially be used for early diagnosis of stomach cancer. The sensor is composed of the embedded in a microfluidic device array of microwells filled with ion-exchange polymer microbeads doped with various organic dyes. The optical response of this unique highly diverse sensor is monitored over a broad spectrum, which provides a platform for cross-reactive sensitivity and allows detection of CO2 and NH3 in saliva at ppm levels. Copyright © 2014 Elsevier B.V. All rights reserved.

Identification of aldo-keto reductase (AKR7A1) and glutathione S-transferase pi (GSTP1) as novel renal damage biomarkers following exposure to mercury.

PubMed

Shin, Y-J; Kim, K-A; Kim, E-S; Kim, J-H; Kim, H-S; Ha, M; Bae, O-N

2017-01-01

The kidney is one of the main targets for toxicity induced by xenobiotics. Sensitive detection of early impairment is critical to assess chemical-associated renal toxicity. The aim of this study was to identify potential nephrotoxic biomarkers in rat kidney tissues after exposure to mercury (Hg), a representative nephrotoxicant, and to evaluate these new biomarkers employing in vivo and in vitro systems. Mercuric chloride was administered orally to Sprague-Dawley rats for 2 weeks. Proteomic analysis revealed that aldo-keto reductase (AKR7A1) and glutathione S-transferase pi (GSTP1) were significantly elevated in kidney after Hg exposure. While the levels of conventional nephrotoxic clinical markers including blood urea nitrogen and serum creatinine were not elevated, the mRNA and protein levels of AKR7A1 and GSTP1 were increased upon Hg exposure in a dose-dependent manner. The increases in AKR7A1 and GSTP1 were also observed in rat kidneys after an extended exposure for 6 weeks to low-dose Hg. In in vitro rat kidney proximal tubular cells, changes in AKR7A1 and GSTP1 levels correlated well with the extent of cytotoxicity induced by Hg, cadmium, or cisplatin. AKR7A1 and GSTP1 were identified as new candidates for Hg-induced nephrotoxicity, suggesting that these biomarkers have potential for evaluating or predicting nephrotoxicity.

Chronic fluoride exposure exacerbates headkidney pathology and causes immune commotion in Clarias gariepinus.

PubMed

Singh, Rashmi; Hussain, Md Arafat; Kumar, Jai; Kumar, Manmohan; Kumari, Usha; Mazumder, Shibnath

2017-11-01

The current study was aimed to understand the effects of chronic fluoride exposure on fish immune system. African sharp tooth catfish (Clarias gariepinus) were exposed to 73.45mg/L of fluoride corresponding to 1/10 96h LC 50 for 30 d and the effects on general fish health and several immune parameters were studied. Chronic fluoride exposure led to significant alteration in serum biochemical parameters including alkaline phosphatase, alanine transaminase, aspartate transaminase, triglycerides, cholesterol and blood urea nitrogen levels revealing the detrimental effect of fluoride on general fish health. Upregulation in cytochrome P450 1A expression, both at mRNA and protein level suggested that fluoride activates the detoxification machinery in headkidney (HK) of C. gariepinus. Histopathological analysis of HK from exposed fish further revealed fluoride-induced hypertrophy, increase in melano-macrophage centers (MMCs) and the development of cell-depleted regions. Fluoride reduced headkidney somatic index (HKSI) and the phagocytic potential of headkidney macrophages (HKM). It induced caspase-3-dependent headkidney leukocyte (HKL) apoptosis, elevated superoxide generation and production of pro-inflammatory cytokine TNF-α besides suppressed T-cell proliferation in the exposed fish. We surmise the elevation in superoxide levels coupled with increased TNF-α production to be plausible causes of fluoride-induced HKL apoptosis. It is concluded that chronic fluoride exposure induces structure-function alterations in HK, the primary lymphoid organ in fish leading to impairment in immune responses. Copyright © 2017. Published by Elsevier B.V.

Biochemical alterations induced by oral subchronic exposure to fipronil, fluoride and their combination in buffalo calves.

PubMed

Gill, Kamalpreet Kaur; Dumka, Vinod Kumar

2013-11-01

The effects of various pesticides and minerals on biochemical parameters have been explored in different species, but hardly any data exist regarding the combined toxicological effect of pesticides and minerals on these parameters in animals. The present study investigated the effects of fipronil and fluoride co-exposure on biochemical parameters in buffalo calves. Twenty-four healthy male buffalo calves divided into four groups were treated for 98 consecutive days. Group I, receiving no treatment served as the control. Animals of groups II and III were orally administered with fipronil @ 0.5mg/kg/day and sodium fluoride (NaF) @ 6.67 mg/kg/day, respectively, for 98 days. An additional group IV was co-administered fipronil and NaF at the same dosages as groups II and III. Administration of fipronil alone produced mild toxic signs, significant elevation in plasma proteins, blood glucose, blood urea nitrogen (BUN) and significant decline in the plasma cholesterol levels. NaF exposure produced toxic signs specifically of muscle weakness and brown and black discoloration of teeth. Significant elevation was seen in whole blood cholinesterase, BUN and creatinine levels. However, it produced significant decline in blood glucose, cholesterol and plasma protein levels. Combined exposure to fipronil and sodium fluoride produced toxic signs with greater intensity while biochemical alterations produced were similar to those that were produced by their individual exposures. Copyright © 2013 Elsevier B.V. All rights reserved.

SIMPLIFIED METHOD FOR EXTRACTING BOUND PESTICIDES FROM AVIAN SERUM

EPA Science Inventory

A simple solid-phase extraction (SPE) method was developed to extract organochlorine pesticides (OCs) and persistent organic pollutants (POPs) from avian serum. In this method, a 1-mL serum sample fortified with two levels of OCs or POPs was treated with 8M urea or 4M urea and 4...

Mechanistic insights into the urea-induced denaturation of kinase domain of human integrin linked kinase.

PubMed

Syed, Sunayana Begum; Khan, Faez Iqbal; Khan, Sabab Hasan; Srivastava, Saurabha; Hasan, Gulam Mustafa; Lobb, Kevin A; Islam, Asimul; Ahmad, Faizan; Hassan, Md Imtaiyaz

2018-05-01

Integrin-linked kinase (ILK), a ubiquitously expressed intracellular Ser/Thr protein kinase, plays a major role in the oncogenesis and tumour progression. The conformational stability and unfolding of kinase domain of ILK (ILK 193-446 ) was examined in the presence of increasing concentrations of urea. The stability parameters of the urea-induced denaturation were measured by monitoring changes in [θ] 222 (mean residue ellipticity at 222nm), difference absorption coefficient at 292nm (Δε 292 ) and intrinsic fluorescence emission intensity at pH7.5 and 25±0.1°C. The urea-induced denaturation was found to be reversible. The protein unfolding transition occurred in the urea concentration range 3.0-7.0M. A coincidence of normalized denaturation curves of optical properties ([θ] 222 , Δε 292 and λ max , the wavelength of maximum emission intensity) suggested that urea-induced denaturation of kinase domain of ILK is a two-state process. We further performed molecular dynamics simulation for 100ns to see the effect of urea on structural stability of kinase domain of ILK at atomic level. Structural changes with increasing concentrations of urea were analysed, and we observed a significant increase in the root mean square deviation, root mean square fluctuations, solvent accessible surface area and radius of gyration. A correlation was observed between in vitro and in silico studies. Copyright © 2018 Elsevier B.V. All rights reserved.

A method to solubilise protein aggregates for immunoassay quantification which overcomes the neurofilament "hook" effect.

PubMed

Lu, Ching-Hua; Kalmar, Bernadett; Malaspina, Andrea; Greensmith, Linda; Petzold, Axel

2011-02-15

Neurofilament (Nf) aggregates are a common pathological feature of neurodegenerative disorders. Although Nf levels have been investigated as a potential disease biomarker, Nf aggregates may mask Nf epitopes, preventing accurate quantification by immunoassay. Using the SOD1(G93A) mouse model of amyotrophic lateral sclerosis, we developed a method to disrupt Nf aggregates, allowing optimal immunoassay performance. Phosphorylated (NfH(SMI35)) and hyperphosphorylated (NfH(SMI34)) Nf levels in plasma from 120-day SOD1(G93A) mice were quantified using an in-house ELISA modified for use with small volumes. Different pre-analytical methods were tested for their ability to solubilize Nf aggregates and immunoblotting was used for qualitative analysis. A 'hook effect' was observed for serially diluted plasma samples quantified using an ELISA originally developed for CSF samples. Immunoblotting confirmed the existence of high molecular-weight NfH aggregates in plasma and the resolving effect of timed urea on these aggregates. Thermostatic (pre-thawing) and chemical (calcium chelators, urea) pre-analytical processing of samples had variable success in disrupting NfH aggregates. Timed urea-calcium chelator incubation yielded the most consistent plasma NfH levels. A one hour sample pre-incubation with 0.5M urea in Barbitone-EDTA buffer at room temperature resolved the "hook effect" without compromising the ELISA. In SOD1(G93A) mice, median levels of NfH(SMI34) were over 10-fold and NfH(SMI35) levels 5-fold greater than controls. NfH aggregates can be solubilised and the "hook effect" abolished by a one-hour sample pre-incubation in a urea-calcium chelator-enriched buffer. This method is applicable for quantification of NfH phosphoforms in experimental and disease settings where Nf aggregate formation occurs. © 2010 Elsevier B.V. All rights reserved.

Is elevated Red cell distribution width a prognostic predictor in adult patients with community acquired Pneumonia?

PubMed Central

2014-01-01

Background Community acquired pneumonia (CAP) is a major cause of morbidity and mortality. We recently demonstrated that among young patients (<60 years old) with CAP, elevated red blood cell distribution width (RDW) level on admission was associated with significant higher rates of mortality and severe morbidity. We aimed to investigate the prognostic predictive value of RDW among CAP patients in general population of internal wards. Methods The cohort included patients of 18 years old or older who were diagnosed with CAP (defined as pneumonia identified 48 hours or less from hospitalization) between January 1, 2005 and December 31, 2010. Patients were retrospectively analyzed for risk factors for a primary endpoint of 90-day mortality. Secondary endpoint was defined as complicated hospitalization (defined as at least one of the following: In- hospital mortality, length of stay of at least 10 days or ICU admission). Binary logistic regression analysis was used for the calculation of the odds ratios (OR) and p values in univariate and multivariate analysis to identify association between patient characteristic, 90-day mortality and complicated hospitalization. Results The cohort included 3815 patients. In univariate analysis, patients with co-morbid conditions tended to have a complicated course of CAP. In multivariate regression analysis, variables associated with an increased risk of 90-day mortality included age > 70 years, high Charlson comorbidity index (>2), Hb < 10 mg/dl, Na <130 meq/l, blood urea nitrogen (BUN) >30 mg/dl, systolic blood pressure < 90 mmHg and elevated RDW >15%. Variables associated with complicated hospitalization included high Charlson comorbidity index, BUN > 30 mg/dl, hemoglobin < 10 g/dl, heart rate >124 bpm, systolic blood pressure < 90 mmHg and elevated RDW. Mortality rate and complicated hospitalization were significantly higher among patients with increased RDW regardless of the white blood cell count or hemoglobin levels. Conclusions Elevated RDW levels on admission are associated with significant higher rates of mortality and severe morbidity in adult patients with CAP. RDW as a prognostic marker was unrelated with hemoglobin levels, WBC count, age or Charlson score. PMID:24597687

Effects on milk urea concentration, urine output, and drinking water intake from incremental doses of potassium bicarbonate fed to mid-lactation dairy cows.

PubMed

Eriksson, T; Rustas, B-O

2014-07-01

Large variation exists in the potassium content of dairy cow feeds and also within a feed type due to soil type and fertilization. Increased ration K concentration causes a subsequent increase in urinary volume and could be expected to also lower milk urea concentration. Six multiparous mid-lactation Swedish Red dairy cows, all fitted with rumen cannulas, were subjected to 3 different levels of K intake in a Latin square experiment with three 2-wk periods to evaluate the effects on concentrations of milk urea and rumen ammonia, urinary output, and drinking water intake. The treatments were achieved by K supplementation on top of a low-K basal ration fed at individual allowances fixed throughout the experiment. The basal ration, consumed at 20.2 kg of dry matter (DM)/d, provided 165 g of crude protein/kg of DM and consisted of grass silage, concentrates, and urea in the proportions 39.3:60.0:0.7 on a DM basis. Potassium bicarbonate supplementation was 0, 616, and 1,142 g/d, respectively, to give total ration K concentrations that were low (LO; 12 g/kg of DM), medium (MED; 23 g/kg of DM), or high (HI; 32 g/kg of DM). Production and composition of milk was not affected by treatment. A linear effect on milk urea concentration was detected, being 4.48, 4.18, and 3.77 mM for LO, MED, and HI, respectively, and a linear tendency for rumen ammonia concentration with 6.65, 6.51, and 5.84 mg of NH₃-N/dL for LO, MED, and HI, respectively. Milk urea concentration peaked about 3h after the rumen ammonia peak from the morning feeding, at a level 1.3mM over the baseline. Urinary urea excretion declined linearly (105, 103, and 98 g of urea-N/d for LO, MED, and HI, respectively). Linear increases occurred in urinary output (0.058 ± 0.001 kg of urine/g of K intake; no intercept; coefficient of determination=0.997) and drinking water intake (65.9 ± 2.02 + 0.069 ± 0.004 kg of water/g of K intake; coefficient of determination=0.95). Urinary K concentration leveled off at 12.4 g/L. Urinary creatinine excretion was not affected by K addition, but allantoin excretion increased linearly by 27% from LO to HI, suggesting increased rumen microbial growth. Rumen pH, acetate proportion of total volatile fatty acids, and digestibility of DM, organic matter, and neutral detergent fiber increased linearly with increasing potassium intake. We concluded that increased ration K concentration lowers milk urea concentration with a magnitude significant for the interpretation of milk urea values, but other sources of variation, such as sampling time relative to feeding, may be even more important. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Effects of rumen undegradable protein supplementation on productive performance and indicators of protein and energy metabolism in Holstein fresh cows.

PubMed

Amanlou, H; Farahani, T Amirabadi; Farsuni, N Eslamian

2017-05-01

The objective of this study was to determine the effects of feeding increased dietary crude protein (CP) on productive performance and indicators of protein and energy metabolism during 21 d postpartum. Thirty multiparous Holstein dairy cows were balanced by previous lactation milk yield, body condition score (BCS) at calving, and parity and randomly allocated to 1 of 3 dietary treatments from calving until 21 d postpartum. Dietary treatments were 16.0% CP with 5.0% rumen undegradable protein (RUP) based on dry matter (DM) (16CP), 18.7% CP with 7.0% RUP based on DM (19CP), and 21.4% CP with 9.0% RUP based on DM (21CP). Diets were similar in net energy for lactation (approximately 1.7 Mcal/kg of DM) and CP levels were increased with corn gluten meal and fish meal. Dry matter intake (DMI) was increased by increasing dietary CP levels from 16.0 to 19.0% of DM, but dietary CP beyond 19.0% had no effect on DMI. Milk yields were 4.7 and 6.5 kg/d greater in cows fed the 19CP and 21CP diets versus those fed the 16CP diet, whereas 4% fat-corrected milk was greater for cows fed the 21CP than the 16CP diet (36.0 vs. 31.4 kg/d). Milk protein content and yield, lactose yield, and milk urea nitrogen were elevated by increased dietary CP. Milk lactose content and fat yield were not different among dietary treatments, but milk fat content tended to decline with increasing content of CP in diets. High CP levels increased milk N secretion but decreased milk N efficiency. Apparent digestibility of DM, CP, and neutral detergent fiber was greater on the 19CP and 21CP diets compared with the 16CP diet. Cows fed the 19CP and 21CP diets lost less body condition relative to those fed the 16CP diet over 21 d postpartum. Feeding higher CP levels increased the concentrations of serum albumin, albumin to globulin ratio, and urea nitrogen and decreased aspartate aminotransferase, nonesterified fatty acids, and β-hydroxybutyrate, but had no effect on globulin, glucose, cholesterol, or triacylglycerol. These findings indicated that elevating dietary CP up to 19.0% of DM using RUP supplements improved DMI, productive performance and the indicators of protein and energy metabolism from calving to 21 d postpartum. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Effects of end-stage renal disease and dialysis modalities on blood ammonia level

PubMed Central

VAZIRI, Nosratola D.; KHAZAELI, Mahyar; NUNES, Ane C. F.; HARLEY, Kevin T.; SAID, Hyder; ALIPOUR, Omeed; LAU, Wei Ling; PAHL, Madeleine V.

2018-01-01

Introduction Uremia results in a characteristic breath odor (uremic fetor) which is largely due to its high ammonia content. Earlier studies have shown a strong correlation between breath ammonia and blood urea levels and a 1 0-fold reduction in breath ammonia after hemodialysis in patients with chronic kidney disease. Potential sources of breath ammonia include: (i) local ammonia production from hydrolysis of urea in the oropharyngeal and respiratory tracts by bacterial flora, and (ii) release of circulating blood ammonia by the lungs. While the effects of uremia and hemodialysis on breath ammonia are well known their effects on blood ammonia are unknown and were explored here. Methods Blood samples were obtained from 23 hemodialysis patients (immediately before and after dialysis), 14 peritoneal dialysis patients, and 10 healthy controls. Blood levels of ammonia, creatinine, urea, and electrolytes were measured. Findings No significant difference was found in baseline blood ammonia between hemodialysis, peritoneal dialysis and control groups. Hemodialysis procedure led to a significant reduction in urea concentration (P<0.001) which was paradoxically accompanied by a modest but significant (P<0.05) rise in blood ammonia level in 10 of the 23 patients studied. Change in blood ammonia pre- and post-hemodialysis correlated with change in serum bicarbonate levels (r=0.61, P<0.01). On subgroup analysis of patients who had a rise in blood ammonia levels after dialysis, there was a strong correlation with drop in mean arterial pressure (r=0.88, P<0.01). The nadir intradialytic systolic blood pressure trended lower in the hemodialysis patients who had a rise in blood ammonia compared to the patients who manifested a fall in blood ammonia (124±8vs.136±6mmHg respectively, P=0.27). Discussion Fall in blood urea following hemodialysis in ESRD patients was paradoxically accompanied by a modest rise in blood ammonia levels in 43% of the patients studied, contrasting prior reported effects of hemodialysis on breath ammonia. In this subgroup of patients, changes in blood ammonia during hemodialysis correlated with rise in blood bicarbonate and fall in mean arterial blood pressure. PMID:27804262

Effects of end-stage renal disease and dialysis modalities on blood ammonia level.

PubMed

Vaziri, Nosratola D; Khazaeli, Mahyar; Nunes, Ane C F; Harley, Kevin T; Said, Hyder; Alipour, Omeed; Lau, Wei Ling; Pahl, Madeleine V

2017-07-01

Uremia results in a characteristic breath odor (uremic fetor) which is largely due to its high ammonia content. Earlier studies have shown a strong correlation between breath ammonia and blood urea levels and a 10-fold reduction in breath ammonia after hemodialysis in patients with chronic kidney disease. Potential sources of breath ammonia include: (i) local ammonia production from hydrolysis of urea in the oropharyngeal and respiratory tracts by bacterial flora, and (ii) release of circulating blood ammonia by the lungs. While the effects of uremia and hemodialysis on breath ammonia are well known their effects on blood ammonia are unknown and were explored here. Blood samples were obtained from 23 hemodialysis patients (immediately before and after dialysis), 14 peritoneal dialysis patients, and 10 healthy controls. Blood levels of ammonia, creatinine, urea, and electrolytes were measured. No significant difference was found in baseline blood ammonia between hemodialysis, peritoneal dialysis and control groups. Hemodialysis procedure led to a significant reduction in urea concentration (P < 0.001) which was paradoxically accompanied by a modest but significant (P < 0.05) rise in blood ammonia level in 10 of the 23 patients studied. Change in blood ammonia pre- and post-hemodialysis correlated with change in serum bicarbonate levels (r = 0.61, P < 0.01). On subgroup analysis of patients who had a rise in blood ammonia levels after dialysis, there was a strong correlation with drop in mean arterial pressure (r = 0.88, P < 0.01). The nadir intradialytic systolic blood pressure trended lower in the hemodialysis patients who had a rise in blood ammonia compared to the patients who manifested a fall in blood ammonia (124 ± 8 vs. 136 ± 6 mmHg respectively, P = 0.27). Fall in blood urea following hemodialysis in ESRD patients was paradoxically accompanied by a modest rise in blood ammonia levels in 43% of the patients studied, contrasting prior reported effects of hemodialysis on breath ammonia. In this subgroup of patients, changes in blood ammonia during hemodialysis correlated with rise in blood bicarbonate and fall in mean arterial blood pressure. © 2016 International Society for Hemodialysis.

Different urea stoichiometries between the dissociation and denaturation of tobacco mosaic virus as probed by hydrostatic pressure.

PubMed

Santos, Jose L R; Aparicio, Ricardo; Joekes, Inés; Silva, Jerson L; Bispo, Jose A C; Bonafe, Carlos F S

2008-05-01

Viruses are very efficient self-assembly structures, but little is understood about the thermodynamics governing their directed assembly. At higher levels of pressure or when pressure is combined with urea, denaturation occurs. For a better understanding of such processes, we investigated the apparent thermodynamic parameters of dissociation and denaturation by assuming a steady-state condition. These processes can be measured considering the decrease of light scattering of a viral solution due to the dissociation process, and the red shift of the fluorescence emission spectra, that occurs with the denaturation process. We determined the apparent urea stoichiometry considering the equilibrium reaction of TMV dissociation and subunit denaturation, which furnished, respectively, 1.53 and 11.1 mol of urea/mol of TMV subunit. The denaturation and dissociation conditions were arrived in a near reversible pathway, allowing the determination of thermodynamic parameters. Gel filtration HPLC, electron microscopy and circular dichroism confirmed the dissociation and denaturation processes. Based on spectroscopic results from earlier papers, the calculation of the apparent urea stoichiometry of dissociation and denaturation of several other viruses resulted in similar values, suggesting a similar virus-urea interaction among these systems.

Bmi-1 plays a critical role in the protection from acute tubular necrosis by mobilizing renal stem/progenitor cells.

PubMed

Lv, Xianhui; Yu, Zhenzhen; Xie, Chunfeng; Dai, Xiuliang; Li, Qing; Miao, Dengshun; Jin, Jianliang

2017-01-22

The regeneration of injured tubular cell occurs primarily from intrinsic renal stem/progenitor cells (RSCs) labeled with CD24 and CD133 after acute tubular necrosis (ATN). Bmi-1 plays a crucial role in regulating self-renewal, differentiation and aging of multiple adult stem cells and progenitor cells. Bmi-1 was rapidly elevated in the induction of adult kidney regeneration by renal injury. To determine whether Bmi-1 maintained mobilization of RSCs in the protection from ATN, glycerol-rhabdomyolysis-induced ATN were performed in wild type (WT) and Bmi-1-deficient (Bmi-1 -/- ) mice. Their ATN phenotypes were analyzed; CD24 and CD133 double positive (CD24 + CD133 + ) cells were measured; and the levels of serum urea nitrogen (SUN) and serum creatinine (SCr) were detected. We found that CD24 + CD133 + RSCs were mobilized in WT ATN mice with the increased expression of Bmi-1; Bmi-1 deficiency led to increased tubular cast formation and necrosis, elevated levels of SUN and SCr, decreased tubular proliferation, and immobilized ratio of RSCs in ATN. These findings indicated that Bmi-1 played a critical role in the protection from ATN by maintaining mobilization of RSCs and would be a novel therapeutic target for preventing the progression of ATN. Copyright © 2016 Elsevier Inc. All rights reserved.

Bmi-1 plays a critical role in the protection from acute tubular necrosis by mobilizing renal stem/progenitor cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lv, Xianhui; Yu, Zhenzhen; Xie, Chunfeng

The regeneration of injured tubular cell occurs primarily from intrinsic renal stem/progenitor cells (RSCs) labeled with CD24 and CD133 after acute tubular necrosis (ATN). Bmi-1 plays a crucial role in regulating self-renewal, differentiation and aging of multiple adult stem cells and progenitor cells. Bmi-1 was rapidly elevated in the induction of adult kidney regeneration by renal injury. To determine whether Bmi-1 maintained mobilization of RSCs in the protection from ATN, glycerol-rhabdomyolysis-induced ATN were performed in wild type (WT) and Bmi-1-deficient (Bmi-1{sup −/−}) mice. Their ATN phenotypes were analyzed; CD24 and CD133 double positive (CD24{sup +}CD133{sup +}) cells were measured; andmore » the levels of serum urea nitrogen (SUN) and serum creatinine (SCr) were detected. We found that CD24{sup +}CD133{sup +} RSCs were mobilized in WT ATN mice with the increased expression of Bmi-1; Bmi-1 deficiency led to increased tubular cast formation and necrosis, elevated levels of SUN and SCr, decreased tubular proliferation, and immobilized ratio of RSCs in ATN. These findings indicated that Bmi-1 played a critical role in the protection from ATN by maintaining mobilization of RSCs and would be a novel therapeutic target for preventing the progression of ATN.« less

Effects of combination of aliskiren and pentoxyfylline on renal function in the rat remnant kidney model of chronic renal failure.

PubMed

Soni, Hitesh M; Patel, Praful P; Patel, Savan; Rath, Akshyaya C; Acharya, Aviseka; Trivedi, Harshkant D; Jain, Mukul R

2015-01-01

The aim was to investigate the nephroprotective effect of combination of aliskiren (ASK), a direct renin inhibitor and pentoxifylline (PTX), inhibitor of tumor necrotic factor-alpha (TNF-alpha), in rat remnant kidney model of chronic kidney disease (CKD). Nephrectomized (NPX) rats were treated with ASK (10 mg/kg, p.o.), PTX (100 mg/kg, p.o.), and combination of PTX + ASK once daily for 28 days. We have performed analysis of various renal injury parameters after 4 weeks of treatment. Treatment with PTX, ASK and combination showed significant improvement in urea, creatinine and total protein in plasma when compared with vehicle treated group in NPX rats. ASK and combination of PTX + ASK elicited significant reduction in blood pressure but PTX alone did not produce blood pressure reduction. ASK treatment showed significant elevation in TNF-alpha, whereas PTX and ASK + PTX showed significant reduction in TNF-alpha in plasma. Histopathologically, the extent of the kidney injury was similar in NPX + vehicle and NPX + ASK-treated rats. PTX and ASK + PTX-treated group showed lesser extent of kidney injury. There was good correlation of mRNA expression levels of kidney injury molecule-1 and bradykinin B1 receptor data with histopathological findings in kidney samples and elevated TNF-alpha levels in plasma. We conclude that combination of PTX + ASK may be better therapeutic intervention for nephroprotection in CKD patients.

Ground Juniperus pinchotii and urea in supplements fed to Rambouillet ewe lambs Part 2: Ewe lamb rumen microbial communities.

PubMed

Ishaq, S L; Yeoman, C J; Whitney, T R

2017-10-01

This study evaluated effects of ground redberry juniper () and urea in dried distillers grains with solubles-based supplements fed to Rambouillet ewe lambs ( = 48) on rumen physiological parameters and bacterial diversity. In a randomized study (40 d), individually-penned lambs were fed ground sorghum-sudangrass hay and of 1 of 8 supplements (6 lambs/treatment; 533 g/d; as-fed basis) in a 4 × 2 factorial design with 4 concentrations of ground juniper (15%, 30%, 45%, or 60% of DM) and 2 levels of urea (1% or 3% of DM). Increasing juniper resulted in minor changes in microbial β-diversity (PERMANOVA, pseudo F = 1.33, = 0.04); however, concentrations of urea did not show detectable broad-scale differences at phylum, family, or genus levels according to ANOSIM ( > 0.05), AMOVA ( > 0.10), and PERMANOVA ( > 0.05). Linear discriminant analysis indicated some genera were specific to certain dietary treatments ( < 0.05), though none of these genera were present in high abundance; high concentrations of juniper were associated with and , low concentrations of urea were associated with , and high concentrations of urea were associated with and . were decreased by juniper and urea. , , and increased with juniper and were positively correlated (Spearman's, < 0.05) with each other but not to rumen factors, suggesting a symbiotic interaction. Overall, there was not a juniper × urea interaction for total VFA, VFA by concentration or percent total, pH, or ammonia ( 0.29). When considering only percent inclusion of juniper, ruminal pH and proportion of acetic acid linearly increased ( < 0.001) and percentage of butyric acid linearly decreased ( = 0.009). Lamb ADG and G:F were positively correlated with (Spearman's, < 0.05) and negatively correlated with Synergistaceae, the BS5 group, and Lentisphaerae. Firmicutes were negatively correlated with serum urea nitrogen, ammonia, total VFA, total acetate, and total propionate. Overall, modest differences in bacterial diversity among treatments occurred in the abundance or evenness of several OTUs, but there was not a significant difference in OTU richness. As diversity was largely unchanged, the reduction in ADG and lower-end BW was likely due t* reduced DMI rather than a reduction in microbial fermentative ability.

Plasma and urine levels of electrolytes, urea and steroid hormones involved in osmoregulation of cetaceans.

PubMed

Birukawa, Naoko; Ando, Hironori; Goto, Mutsuo; Kanda, Naohisa; Pastene, Luis A; Nakatsuji, Hiroki; Hata, Hiroshi; Urano, Akihisa

2005-11-01

Cetaceans are well adapted to their hyperosmotic environment by properly developed osmoregulatory ability. A question here is how they regulate water and mineral balances in marine habitats. In the present study, we determined blood and urine levels of various chemicals involved in osmoregulation, compared them with those in artiodactyls, and characterized the values in the whales. Blood and urine samples obtained from baleen whales of common minke (Balaenoptera acutorostrata), sei (B. borealis), and Bryde's whales (B. brydei), and toothed whales of sperm whales (Physeter macrocephalus) were analyzed for osmolality, major electrolytes, urea, steroid hormones and glucose. The urine osmolality and Na(+) concentrations in the cetaceans were much higher than those in the cattle. Furthermore, the cetaceans had 5 to 11-fold urea in plasma than the cattle, and 2 to 4-fold urea in urine. There were no significant difference in the plasma concentrations of corticosteroids between the cetaceans and the cattle. The present results indicate that the osmoregulatory parameters seem to be not affected by the reproductive stage and sex steroid hormones. The concentrations of urea in plasma and urine of the baleen whales were higher than those of the sperm whales, indicating a possibility that their osmoregulatory mechanisms may be correlated to their feeding habits. The present results suggest that cetaceans have unique osmoregulatory mechanisms by which they excrete strongly hypertonic urine to maintain fluid homeostasis in marine habitats.

Longitudinal Associations among Renal Urea Clearance-Corrected Normalized Protein Catabolic Rate, Serum Albumin, and Mortality in Patients on Hemodialysis.

PubMed

Eriguchi, Rieko; Obi, Yoshitsugu; Streja, Elani; Tortorici, Amanda R; Rhee, Connie M; Soohoo, Melissa; Kim, Taehee; Kovesdy, Csaba P; Kalantar-Zadeh, Kamyar

2017-07-07

There are inconsistent reports on the association of dietary protein intake with serum albumin and outcomes among patients on hemodialysis. Using a new normalized protein catabolic rate (nPCR) variable accounting for residual renal urea clearance, we hypothesized that higher baseline nPCR and rise in nPCR would be associated with higher serum albumin and better survival among incident hemodialysis patients. Among 36,757 incident hemodialysis patients in a large United States dialysis organization, we examined baseline and change in renal urea clearance-corrected nPCR as a protein intake surrogate and modeled their associations with serum albumin and mortality over 5 years (1/2007-12/2011). Median nPCRs with and without accounting for renal urea clearance at baseline were 0.94 and 0.78 g/kg per day, respectively (median within-patient difference, 0.14 [interquartile range, 0.07-0.23] g/kg per day). During a median follow-up period of 1.4 years, 8481 deaths were observed. Baseline renal urea clearance-corrected nPCR was associated with higher serum albumin and lower mortality in the fully adjusted model ( P trend <0.001). Among 13,895 patients with available data, greater rise in renal urea clearance-corrected nPCR during the first 6 months was also associated with attaining high serum albumin (≥3.8 g/dl) and lower mortality ( P trend <0.001); compared with the reference group (a change of 0.1-0.2 g/kg per day), odds and hazard ratios were 0.53 (95% confidence interval, 0.44 to 0.63) and 1.32 (95% confidence interval, 1.14 to 1.54), respectively, among patients with a change of <-0.2 g/kg per day and 1.62 (95% confidence interval, 1.35 to 1.96) and 0.76 (95% confidence interval, 0.64 to 0.90), respectively, among those with a change of ≥0.5 g/kg per day. Within a given category of nPCR without accounting for renal urea clearance, higher levels of renal urea clearance-corrected nPCR consistently showed lower mortality risk. Among incident hemodialysis patients, higher dietary protein intake represented by nPCR and its changes over time appear to be associated with increased serum albumin levels and greater survival. nPCR may be underestimated when not accounting for renal urea clearance. Compared with the conventional nPCR, renal urea clearance-corrected nPCR may be a better marker of mortality. Copyright © 2017 by the American Society of Nephrology.

Final report of the safety assessment of Urea.

PubMed

2005-01-01

Although Urea is officially described as a buffering agent, humectant, and skin-conditioning agent-humectant for use in cosmetic products, there is a report stating that Urea also is used in cosmetics for its desquamating and antimicrobial action. In 2001, the Food and Drug Administration (FDA) reported that Urea was used in 239 formulations. Concentrations of use for Urea ranged from 0.01% to 10%. Urea is generally recognized as safe by FDA for the following uses: side-seam cements for food contact; an inhibitor or stabilizer in pesticide formulations and formulations applied to animals; internal sizing for paper and paperboard and surface sizing and coating of paper and paper board that contact water-in-oil dairy emulsions, low-moisture fats and oils, moist bakery products, dry solids with surface containing no free fats or oil, and dry solids with the surface of fat or oil; and to facilitate fermentation of wine. Urea is the end product of mammalian protein metabolism and the chief nitrogenous compound of urine. Urea concentrations in muscle, liver, and fetuses of rats increased after a subcutaneous injection of Urea. Urea diffused readily through the placenta and into other maternal and fetal organs. The half-life of Urea injected into rabbits was on the order of several hours, and the reutilization rate was 32.2% to 88.8%. Urea given to rats by a bolus injection or continuous infusion resulted in distribution to the following brain regions: frontal lobe, caudate nucleus, hippocampus, thalamus plus hypothalamus, pons and white matter (corpus callosum). The permeability constant after treatment with Urea of whole skin and the dermis of rabbits was 2.37 +/- 0.13 (x 10(6)) and 1.20 +/- 0.09 (x10(3)) cm/min, respectively. The absorption of Urea across normal and abraded human skin was 9.5% +/- 2.3% and 67.9% +/- 5.6%, respectively. Urea increased the skin penetration of other compounds, including hydrocortisone. No toxicity was observed for Urea at levels as high as 2000 mg/kg in acute oral studies using female rats or mice. No signs of toxicity were observed in male piglets dosed orally with up to 4 g/kg Urea for 5 days. Dogs dosed orally with 5 to 30 g/L Urea for 4 to 10 days had signs of toxicity, including weakness, anorexia, vomiting and retching, diarrhea and a decreased body temperature, which led to a deep torpor or coma. No significant microscopic changes were observed in the skin of male nude mice dermally exposed to 100% Urea for 24 h. No observable effect on fetal development was seen in rats and mice dosed orally with an aqueous solution of Urea (2000 mg/kg) on days 10 and 12 of gestation. The mean number of implants, live fetuses, percent fetal resorptions, mean fetal weight, and percent fetuses malformed were comparable to control group. A detergent containing 15% Urea was injected into pregnant ICR-JCl mice and dams and fetuses had no significant differences when compared to control animals. Urea given orally did not enhance the developmental toxicity of N-nitrosomethylurea. Female Sprague-Dawley rats injected in the uterine horn with 0.05 ml Urea on day 3 (preimplantation) or on day 7 (post implantation) exhibited no maternal mortality or morbidity; a dose-dependent reduction in embryo survival was seen with preimplantation treatment. Urea injected intra-amniotically induces mid-trimester abortions in humans. Urea was not genotoxic in several bacterial and mammalian assays; although in assays where Urea was used at a high concentration, genotoxicity was found, many in in vitro assays. Urea is commonly used in studies of DNA because it causes uncoiling of DNA molecules. Urea was not carcinogenic in Fisher 344 rats or C57B1/6 mice fed diets containing up to 4.5% Urea. Exposure of normal human skin to 60% Urea produced no significant irritation in one study, but 5% Urea was slightly irritating and 20% Urea was irritating in other reports. Burning sensations are the most frequently reported effect of Urea used alone or with other agents in treatment of diseased skin. Overall, there are few reports of sensitization among the many clinical studies that report use of Urea in treatment of diseased skin. The Cosmetic Ingredient Review (CIR) Expert Panel determined the data provided in this report to be sufficient to assess the safety of Urea. The Panel did note that Urea can cause uncoiling of DNA, a property used in many DNA studies, but concluded that this in vitro activity is not linked to any in vivo genotoxic activity. Although noting that formulators should be aware that Urea can increase the percutaneous absorption of other chemicals, the CIR Expert Panel concluded that Urea is safe as used in cosmetic products.

Chronotherapeutic effect of fisetin on expression of urea cycle enzymes and inflammatory markers in hyperammonaemic rats.

PubMed

Subramanian, Perumal; Jayakumar, Murugesan; Jayapalan, Jaime Jacqueline; Hashim, Onn Haji

2014-12-01

Elevated blood ammonia leads to hyperammonaemia that affects vital central nervous system (CNS) functions. Fisetin, a naturally occurring flavonoid, exhibits therapeutic benefits, such as anti-cancer, anti-diabetic, anti-oxidant, anti-angiogenic, neuroprotective and neurotrophic effects. In this study, the chronotherapeutic effect of fisetin on ammonium chloride (AC)-induced hyperammonaemic rats was investigated, to ascertain the time point at which the maximum drug effect is achieved. The anti-hyperammonaemic potential of fisetin (50mg/kg b.w. oral) was analysed when administered to AC treated (100mg/kg b.w. i.p.) rats at 06:00, 12:00, 18:00 and 00:00h. Amelioration of pathophysiological conditions by fisetin at different time points was measured by analysing the levels of expression of liver urea cycle enzymes (carbamoyl phosphate synthetase-I (CPS-I), ornithine transcarbamoylase (OTC) and argininosuccinate synthetase (ASS)), nuclear transcription factor kappaB (NF-κB p65), brain glutamine synthetase (GS) and inducible nitric oxide synthase (iNOS) by Western blot analysis. Fisetin increased the expression of CPS-I, OTC, ASS and GS and decreased iNOS and NF-κB p65 in hyperammonaemic rats. Fisetin administration at 00:00h showed more significant effects on the expression of liver and brain markers, compared with other time points. Fisetin could exhibit anti-hyperammonaemic effect owing to its anti-oxidant and cytoprotective influences. The temporal variation in the effect of fisetin could be due to the (i) chronopharmacological, chronopharmacokinetic properties of fisetin and (ii) modulations in the endogenous circadian rhythms of urea cycle enzymes, brain markers, redox enzymes and renal clearance during hyperammonaemia by fisetin. However, future studies in these lines are necessitated. Copyright © 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Effect of sodium chloride intake on urine volume, urinary urea excretion, and milk urea concentration in lactating dairy cattle.

PubMed

Spek, J W; Bannink, A; Gort, G; Hendriks, W H; Dijkstra, J

2012-12-01

Milk urea nitrogen (MUN; mg of N/dL) has been shown to be related to excretion of urinary urea N (UUN; g of N/d) and total excretion of urinary N (UN; g of N/d) in dairy cows. In the present experiment, it was hypothesized that MUN and the relationship between MUN and UUN or UN is affected by urine volume as a result of dietary sodium chloride intake. Twelve lactating Holstein-Friesian dairy cows (mean ± SD: milk production 28.1±3.23 kg/d and 190±41 d in milk), of which 4 were fitted with catheters in the urine bladder and jugular vein, were randomly assigned to 4 dietary levels of sodium chloride (3, 9, 14, and 19 g of Na/kg of DM) according to a triple 4×4 Latin square design. Cows were fed at 95% of ad libitum intake, excluding salt addition. Milk was analyzed for MUN and protein content; urine was analyzed for total N, urea, and creatinine content; feces were analyzed for total N and DM content; and blood plasma was analyzed for urea and creatinine content. Creatinine clearance rate (CCR; L/min) and renal urea reabsorption ratio were estimated based on plasma concentrations of urea and creatinine, and total excretion of urea and creatinine in urine. Intake of DM and N, milk production, and milk protein content were (mean ± SD), on average, 21.4±1.24 kg/d, 522±32.0 g/d, 25.4±2.53 kg/d, and 3.64±0.186%, respectively. A linear relationship was found between Na intake and urine production [urine (kg/d; mean ± SE)=7.5±4.33+0.136±0.0143 × Na intake (g/d)] and between Na intake and MUN [MUN (mg/dL; mean ± SE)=13.5±0.35-0.0068±0.00104 × Na intake (g/d)]. Despite the decrease in MUN with increased Na intake, UN excretion increased linearly with Na intake. Excretion of UUN was not affected by dietary Na content. A linear plateau relationship was observed between CCR and renal urea reabsorption. An increase in CCR coincided with an increase in calculated renal urea reabsorption until a CCR breakpoint value (mean ± SD) of 1.56±0.063 L/min was reached. We conclude that Na intake is negatively related to MUN, whereas UUN is not affected. Variation in mineral intake levels that affect urine volume should, therefore, be taken into account when using MUN as an indicator of UUN in dairy cattle. Copyright © 2012 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Multiple correlation analyses of metabolic and endocrine profiles with fertility in primiparous and multiparous cows.

PubMed

Wathes, D C; Bourne, N; Cheng, Z; Mann, G E; Taylor, V J; Coffey, M P

2007-03-01

Results from 4 studies were combined (representing a total of 500 lactations) to investigate the relationships between metabolic parameters and fertility in dairy cows. Information was collected on blood metabolic traits and body condition score at 1 to 2 wk prepartum and at 2, 4, and 7 wk postpartum. Fertility traits were days to commencement of luteal activity, days to first service, days to conception, and failure to conceive. Primiparous and multiparous cows were considered separately. Initial linear regression analyses were used to determine relationships among fertility, metabolic, and endocrine traits at each time point. All metabolic and endocrine traits significantly related to fertility were included in stepwise multiple regression analyses alone (model 1), including peak milk yield and interval to commencement of luteal activity (model 2), and with the further addition of dietary group (model 3). In multiparous cows, extended calving to conception intervals were associated prepartum with greater concentrations of leptin and lesser concentrations of nonesterified fatty acids and urea, and postpartum with reduced insulin-like growth factor-I at 2 wk, greater urea at 7 wk, and greater peak milk yield. In primiparous cows, extended calving to conception intervals were associated with more body condition and more urea prepartum, elevated urea postpartum, and more body condition loss by 7 wk. In conclusion, some metabolic measurements were associated with poorer fertility outcomes. Relationships between fertility and metabolic and endocrine traits varied both according to the lactation number of the cow and with the time relative to calving.

Regulation of Urea Transporters by Tonicity-responsive Enhancer Binding Protein

PubMed Central

Kwon, H. Moo; Kim, Jim

2007-01-01

Urea accumulation in the renal inner medulla plays a key role in the maintenance of maximal urinary concentrating ability. Urea transport in the kidney is mediated by transporter proteins that include renal urea transporter (UT-A) and erythrocyte urea transporter (UT-B). UT-A1 and UT-A2 are produced from the same gene. There is an active tonicity-responsive enhancer (TonE) in the promoter of UT-A1, and the UT-A1 promoter is stimulated by hypertonicity via tonicity-responsive enhancer binding protein (TonEBP). The downregulation of UT-A2 raises the possibility that TonEBP also regulates its promoter. There is some evidence that TonEBP regulates expression of UT-A in vivo; (1) during the renal development of the urinary concentrating ability, expression of TonEBP precedes that of UT-A1; (2) in transgenic mice expressing a dominant negative form of TonEBP, expression of UT-A1 and UT-A2 is severely impaired; (3) in treatment with cyclosporine A, TonEBP was significantly downregulated after 28 days. This downregulation involves mRNA levels of UT-A2; (4) in hypokalemic animals, downregulation of TonEBP contributed to the down regulation of UT-A in the inner medulla. These data support that TonEBP directly contributes to the urinary concentration and renal urea recycling by the regulation of urea transporters. PMID:24459497

Organic and inorganic fertilizer effect on soil CO2 flux, microbial biomass, and growth of Nigella sativa L.

NASA Astrophysics Data System (ADS)

Salehi, Aliyeh; Fallah, Seyfollah; Sourki, Ali Abasi

2017-01-01

Cattle manure has a high carbon/nitrogen ratio and may not decompose; therefore, full-dose application of urea fertilizer might improve biological properties by increasing manure decomposition. This study aimed to investigate the effect of combining cattle manure and urea fertilizer on soil CO2 flux, microbial biomass carbon, and dry matter accumulation during Nigella sativa L. (black cumin) growth under field conditions. The treatments were control, cattle manure, urea, different levels of split and full-dose integrated fertilizer. The results showed that integrated application of cattle manure and chemical fertilizer significantly increased microbial biomass carbon by 10%, soil organic carbon by 2.45%, total N by 3.27%, mineral N at the flowering stage by 7.57%, and CO2 flux by 9% over solitary urea application. Integrated application increased microbial biomass carbon by 10% over the solitary application and the full-dose application by 5% over the split application. The soil properties and growth parameters of N. sativa L. benefited more from the full-dose application than the split application of urea. Cattle manure combined with chemical fertilizer and the full-dose application of urea increased fertilizer efficiency and improved biological soil parameters and plant growth. This method decreased the cost of top dressing urea fertilizer and proved beneficial for the environment and medicinal plant health.

The effectiveness of fermented turmeric powder in subjects with elevated alanine transaminase levels: a randomised controlled study.

PubMed

Kim, Sang-Wook; Ha, Ki-Chan; Choi, Eun-Kyung; Jung, Su-Young; Kim, Min-Gul; Kwon, Dae-Young; Yang, Hye-Jung; Kim, Min-Jung; Kang, Hee-Joo; Back, Hyang-Im; Kim, Sun-Young; Park, Soo-Hyun; Baek, Hum-Young; Kim, Yong-Jae; Lee, Joon-Yeol; Chae, Soo-Wan

2013-03-08

Previous animal studies have shown that Curcuma longa (turmeric) improves liver function. Turmeric may thus be a promising ingredient in functional foods aimed at improving liver function. The purpose of the study is to investigate the hepatoprotective effect of fermented turmeric powder (FTP) on liver function in subjects with elevated alanine transaminase (ALT) levels. A randomised, double-blind, placebo-controlled trial was conducted between November 2010 and April 2012 at the clinical trial center for functional foods of the Chonbuk National University Hospital. The trial included 60 subjects, 20 years old and above, who were diagnosed mild to moderate elevated ALT levels between 40 IU/L and 200 IU/L. Sixty subjects were randomised to receive FTP 3.0 g per day or placebo 3.0 g per day for 12 weeks. The treatment group received two capsules of FTP three times a day after meals, for 12 weeks. The primary efficacy endpoint was change in the ALT levels in the two groups. The secondary efficacy endpoints included its effect on aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), total bilirubin (TB), and lipid profiles. Safety was assessed throughout the study using ongoing laboratory tests. Adverse events (AEs) were also recorded. Sixty subjects were randomised in the study (30 into the FTP group, 30 into the placebo group), and among them, twelve subjects were excluded from the analysis for protocol violation, adverse events or consent withdrawal. The two groups did not differ in baseline characteristics. After 12 weeks of treatment, 48 subjects were evaluated. Of the 48 subjects, 26 randomly received FTP capsules and 22 received placebo. The FTP group showed a significant reduction in ALT levels after 12 weeks of treatment compared with the placebo group (p = 0.019). There was also observed that the serum AST levels were significantly reduce in the FTP group than placebo group (p = 0.02). The GGT levels showed a tendency to decrease, while the serum alkaline phosphatase (ALP), TB, and lipids levels were not modified. There were no reported severe AEs during this study, or abnormalities observed on blood glucose, total protein, albumin, blood urea nitrogen (BUN), and creatinine levels. The data of this trial indicate that FTP is effective and safe, generally well-tolerated without severe AEs, in the treatment of subjects with elevated ALT levels over a 12 weeks period. ClinicalTrials.gov: NCT01634256

The effectiveness of fermented turmeric powder in subjects with elevated alanine transaminase levels: a randomised controlled study

PubMed Central

2013-01-01

Background Previous animal studies have shown that Curcuma longa (turmeric) improves liver function. Turmeric may thus be a promising ingredient in functional foods aimed at improving liver function. The purpose of the study is to investigate the hepatoprotective effect of fermented turmeric powder (FTP) on liver function in subjects with elevated alanine transaminase (ALT) levels. Methods A randomised, double-blind, placebo-controlled trial was conducted between November 2010 and April 2012 at the clinical trial center for functional foods of the Chonbuk National University Hospital. The trial included 60 subjects, 20 years old and above, who were diagnosed mild to moderate elevated ALT levels between 40 IU/L and 200 IU/L. Sixty subjects were randomised to receive FTP 3.0 g per day or placebo 3.0 g per day for 12 weeks. The treatment group received two capsules of FTP three times a day after meals, for 12 weeks. The primary efficacy endpoint was change in the ALT levels in the two groups. The secondary efficacy endpoints included its effect on aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), total bilirubin (TB), and lipid profiles. Safety was assessed throughout the study using ongoing laboratory tests. Adverse events (AEs) were also recorded. Results Sixty subjects were randomised in the study (30 into the FTP group, 30 into the placebo group), and among them, twelve subjects were excluded from the analysis for protocol violation, adverse events or consent withdrawal. The two groups did not differ in baseline characteristics. After 12 weeks of treatment, 48 subjects were evaluated. Of the 48 subjects, 26 randomly received FTP capsules and 22 received placebo. The FTP group showed a significant reduction in ALT levels after 12 weeks of treatment compared with the placebo group (p = 0.019). There was also observed that the serum AST levels were significantly reduce in the FTP group than placebo group (p = 0.02). The GGT levels showed a tendency to decrease, while the serum alkaline phosphatase (ALP), TB, and lipids levels were not modified. There were no reported severe AEs during this study, or abnormalities observed on blood glucose, total protein, albumin, blood urea nitrogen (BUN), and creatinine levels. Conclusion The data of this trial indicate that FTP is effective and safe, generally well-tolerated without severe AEs, in the treatment of subjects with elevated ALT levels over a 12 weeks period. Trial registration ClinicalTrials.gov: http://NCT01634256 PMID:23497020

Changes in Serum Electrolytes, Urea, and Creatinine in Aloe Vera-treated Rats

PubMed Central

Saka, WA; Akhigbe, RE; Popoola, OT; Oyekunle, OS

2012-01-01

This study was carried out to investigate the effect of Aloe vera extract (AvE) on serum electrolytes, urea, and creatinine as indices of renal function in Sprague-Dawley rats. Twelve male Sprague-Dawley rats weighing between 80 and 130 g were used. Rats were divided into two groups: The control and the test groups (n=6). The test group received 1 ml of AvE daily for 28 days. Both the groups fed on standard rat chow and water ad libitum. The results showed a decrease in serum levels of sodium, and potassium, but an increase in the serum levels of bicarbonate, urea, and creatinine in the test group. The changes seen were, however, statistically insignificant, except for the serum levels of sodium and creatinine (P<0.05). It is thus concluded that AvE impairs renal handling of electrolytes with consequent hyponatremia and hypercreatinemia. However, this might be of therapeutic value in conditions associated with hypernatremia. PMID:22754258

Excretory nitrogen metabolism in the juvenile axolotl Ambystoma mexicanum: differences in aquatic and terrestrial environments.

PubMed

Loong, Ai M; Chew, Shit F; Ip, Yuen K

2002-01-01

The fully grown but nonmetamorphosed (juvenile) axolotl Ambystoma mexicanum was ureogenic and primarily ureotelic in water. A complete ornithine-urea cycle (OUC) was present in the liver. Aerial exposure impeded urea (but not ammonia) excretion, leading to a decrease in the percentage of nitrogen excreted as urea in the first 24 h. However, urea and not ammonia accumulated in the muscle, liver, and plasma during aerial exposure. By 48 h, the rate of urea excretion recovered fully, probably due to the greater urea concentration gradient in the kidney. It is generally accepted that an increase in carbamoyl phosphate synthetase activity is especially critical in the developmental transition from ammonotelism to ureotelism in the amphibian. Results from this study indicate that such a transition in A. mexicanum would have occurred before migration to land. Aerial exposure for 72 h exhibited no significant effect on carbamoyl phosphate synthetase-I activity or that of other OUC enzymes (with the exception of ornithine transcarbamoylase) from the liver of the juvenile A. mexicanum. This supports our hypothesis that the capacities of OUC enzymes present in the liver of the aquatic juvenile axolotl were adequate to prepare it for its invasion of the terrestrial environment. The high OUC capacity was further supported by the capability of the juvenile A. mexicanum to survive in 10 mM NH(4)Cl without accumulating amino acids in its body. The majority of the accumulating endogenous and exogenous ammonia was detoxified to urea, which led to a greater than twofold increase in urea levels in the muscle, liver, and plasma and a significant increase in urea excretion by hour 96. Hence, it can be concluded that the juvenile axolotl acquired ureotelism while submerged in water, and its hepatic capacity of urea synthesis was more than adequate to handle the toxicity of endogenous ammonia during migration to land.

Reducing nitrous oxide emissions by changing N fertiliser use from calcium ammonium nitrate (CAN) to urea based formulations.

PubMed

Harty, M A; Forrestal, P J; Watson, C J; McGeough, K L; Carolan, R; Elliot, C; Krol, D; Laughlin, R J; Richards, K G; Lanigan, G J

2016-09-01

The accelerating use of synthetic nitrogen (N) fertilisers, to meet the world's growing food demand, is the primary driver for increased atmospheric concentrations of nitrous oxide (N2O). The IPCC default emission factor (EF) for N2O from soils is 1% of the N applied, irrespective of its form. However, N2O emissions tend to be higher from nitrate-containing fertilisers e.g. calcium ammonium nitrate (CAN) compared to urea, particularly in regions, which have mild, wet climates and high organic matter soils. Urea can be an inefficient N source due to NH3 volatilisation, but nitrogen stabilisers (urease and nitrification inhibitors) can improve its efficacy. This study evaluated the impact of switching fertiliser formulation from calcium ammonium nitrate (CAN) to urea-based products, as a potential mitigation strategy to reduce N2O emissions at six temperate grassland sites on the island of Ireland. The surface applied formulations included CAN, urea and urea with the urease inhibitor N-(n-butyl) thiophosphoric triamide (NBPT) and/or the nitrification inhibitor dicyandiamide (DCD). Results showed that N2O emissions were significantly affected by fertiliser formulation, soil type and climatic conditions. The direct N2O emission factor (EF) from CAN averaged 1.49% overall sites, but was highly variable, ranging from 0.58% to 3.81. Amending urea with NBPT, to reduce ammonia volatilisation, resulted in an average EF of 0.40% (ranging from 0.21 to 0.69%)-compared to an average EF of 0.25% for urea (ranging from 0.1 to 0.49%), with both fertilisers significantly lower and less variable than CAN. Cumulative N2O emissions from urea amended with both NBPT and DCD were not significantly different from background levels. Switching from CAN to stabilised urea formulations was found to be an effective strategy to reduce N2O emissions, particularly in wet, temperate grassland. Copyright © 2016 Elsevier B.V. All rights reserved.

Activated renal tubular Wnt/β-catenin signaling triggers renal inflammation during overload proteinuria.

PubMed

Wong, Dickson W L; Yiu, Wai Han; Chan, Kam Wa; Li, Ye; Li, Bin; Lok, Sarah W Y; Taketo, Makoto M; Igarashi, Peter; Chan, Loretta Y Y; Leung, Joseph C K; Lai, Kar Neng; Tang, Sydney C W

2018-06-01

Imbalance of Wnt/β-catenin signaling in renal cells is associated with renal dysfunction, yet the precise mechanism is poorly understood. Previously we observed activated Wnt/β-catenin signaling in renal tubules during proteinuric nephropathy with an unknown net effect. Therefore, to identify the definitive role of tubular Wnt/β-catenin, we generated a novel transgenic "Tubcat" mouse conditionally expressing stabilized β-catenin specifically in renal tubules following tamoxifen administration. Four weeks after tamoxifen injection, uninephrectomized Tubcat mice displayed proteinuria and elevated blood urea nitrogen levels compared to non-transgenic mice, implying a detrimental effect of the activated signaling. This was associated with infiltration of the tubulointerstitium predominantly by M1 macrophages and overexpression of the inflammatory chemocytokines CCL-2 and RANTES. Induction of overload proteinuria by intraperitoneal injection of low-endotoxin bovine serum albumin following uninephrectomy for four weeks aggravated proteinuria and increased blood urea nitrogen levels to a significantly greater extent in Tubcat mice. Renal dysfunction correlated with the degree of M1 macrophage infiltration in the tubulointerstitium and renal cortical up-regulation of CCL-2, IL-17A, IL-1β, CXCL1, and ICAM-1. There was overexpression of cortical TLR-4 and NLRP-3 in Tubcat mice, independent of bovine serum albumin injection. Finally, there was no fibrosis, activation of epithelial-mesenchymal transition or non-canonical Wnt pathways observed in the kidneys of Tubcat mice. Thus, conditional activation of renal tubular Wnt/β-catenin signaling in a novel transgenic mouse model demonstrates that this pathway enhances intrarenal inflammation via the TLR-4/NLRP-3 inflammasome axis in overload proteinuria. Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Design and synthesis of thienopyrimidine urea derivatives with potential cytotoxic and pro-apoptotic activity against breast cancer cell line MCF-7.

PubMed

Abdelhaleem, Eman F; Abdelhameid, Mohammed K; Kassab, Asmaa E; Kandeel, Manal M

2018-01-01

A series of novel tetrahydrobenzothieno[2,3-d]pyrimidine urea derivatives was synthesized according to fragment-based design strategy. They were evaluated for their anticancer activity against MCF-7 cell line. Three compounds 9c, 9d and 11b showed 1.5-1.03 folds more potent anticancer activity than doxorubicin. In this study, a promising multi-sited enzyme small molecule inhibitor 9c, which showed the most potent anti-proliferative activity, was identified. The anti-proliferative activity of this compound appears to correlate well with its ability to inhibit topoisomerase II (IC 50  = 9.29 μM). Moreover, compound 9c showed excellent VEGFR-2 inhibitory activity, at the sub-micromolar level with IC 50 value 0.2 μM, which is 2.1 folds more potent than sorafenib. Moreover, activation of damage response pathway of the DNA leads to cell cycle arrest at G2/M phase, accumulation of cells in pre-G1 phase and annexin-V and propidium iodide staining, indicating that cell death proceeds through an apoptotic mechanism. Compound 9c showed potent pro-apoptotic effect through induction of the intrinsic mitochondrial pathway of apoptosis. This mechanistic pathway was confirmed by a significant increase in the expression of the tumor suppressor gene p53, elevation in Bax/BCL-2 ratio and a significant increase in the level of active caspase-3. Quantitative structure-activity relationship (QSAR) studies delivered equations of five 3D descriptors with R 2  = 0.814. This QSAR model provides an effective technique for understanding the observed antitumor properties and thus could be adopted for developing effective lead structures. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Argininosuccinate lyase deficiency-argininosuccinic aciduria and beyond.

PubMed

Erez, Ayelet; Nagamani, Sandesh C Sreenath; Lee, Brendan

2011-02-15

The urea cycle consists of six consecutive enzymatic reactions that convert waste nitrogen into urea. Deficiencies of any of these enzymes of the cycle result in urea cycle disorders (UCD), a group of inborn errors of hepatic metabolism that often result in life threatening hyperammonemia. Argininosuccinate lyase (ASL) is a cytosolic enzyme which catalyzes the fourth reaction in the cycle and the first degradative step, that is, the breakdown of argininosuccinic acid to arginine and fumarate. Deficiency of ASL results in an accumulation of argininosuccinic acid in tissues, and excretion of argininosuccinic acid in urine leading to the condition argininosuccinic aciduria (ASA). ASA is an autosomal recessive disorder and is the second most common UCD. In addition to the accumulation of argininosuccinic acid, ASL deficiency results in decreased synthesis of arginine, a feature common to all UCDs except argininemia. Arginine is not only the precursor for the synthesis of urea and ornithine as part of the urea cycle but it is also the substrate for the synthesis of nitric oxide, polyamines, proline, glutamate, creatine, and agmatine. Hence, while ASL is the only enzyme in the body able to generate arginine, at least four enzymes use arginine as substrate: arginine decarboxylase, arginase, nitric oxide synthetase (NOS) and arginine/glycine aminotransferase. In the liver, the main function of ASL is ureagenesis, and hence, there is no net synthesis of arginine. In contrast, in most other tissues, its role is to generate arginine that is designated for the specific cell's needs. While patients with ASA share the acute clinical phenotype of hyperammonemia, encephalopathy, and respiratory alkalosis common to other UCD, they also present with unique chronic complications most probably caused by a combination of tissue specific deficiency of arginine and/or elevation of argininosuccinic acid. This review article summarizes the clinical characterization, biochemical, enzymatic, and molecular features of this disorder. Current treatment, prenatal diagnosis, diagnosis through the newborn screening as well as hypothesis driven future treatment modalities are discussed. Copyright © 2011 Wiley-Liss, Inc.

Emission of ammonia from indoor concrete wall and assessment of human exposure.

PubMed

Bai, Z; Dong, Y; Wang, Z; Zhu, T

2006-04-01

Addition of urea-based antifreeze admixtures during cement mixing can make it possible to produce concrete cement in construction of buildings in cold weather; this, however, has led to increasing indoor air pollution due to continuous transformation and emission from urea to gaseous ammonia in indoor concrete wall. It is believed that ammonia is harmful to human body and exposure to ammonia can cause some serious symptoms such as headaches, burns, and even permanent damage to the eyes and lungs. In order to understand the emission of ammonia from indoor concrete wall in civil building and assess the health risk of people living in these buildings, the experimental pieces of concrete wall were first prepared by concreting cement and urea-based antifreeze admixtures to simulate the indoor wall in civil building in this work. Then environmental chamber was adopted for studying the effect of temperature, relative humility and air exchange rate on emission of ammonia from experimental pieces of concrete wall. Also the field experiment was made at selected rooms in given civil buildings. Exposure and potential dose of adult and children exposed to indoor/outdoor ammonia in summer and in winter are calculated and evaluated by using Scenario Evaluation Approach. The results indicated that high air exchange rate leads to decreased ammonia concentration, and elevation of temperature causes increasing ammonia concentration and volatilizing rate in chamber. The complete emission of ammonia from the wall containing urea-based antifreeze admixtures needs more than 10 years in general. Ventilating or improving air exchange can play a significant role in reducing ammonia concentration in actual rooms in field experiments. Urea-based antifreeze admixtures in concrete wall can give rise to high exposure and potential dose, especially in summer. Generally, adults have a high potential dose than children, while children have personal average dose rate beyond adults in the same conditions.

Denaturant-Dependent Conformational Changes in a [beta]-Trefoil Protein: Global and Residue-Specific Aspects of an Equilibrium Denaturation Process

DOE Office of Scientific and Technical Information (OSTI.GOV)

Latypov, Ramil F.; Liu, Dingjiang; Jacob, Jaby

2010-01-12

Conformational properties of the folded and unfolded ensembles of human interleukin-1 receptor antagonist (IL-1ra) are strongly denaturant-dependent as evidenced by high-resolution two-dimensional nuclear magnetic resonance (NMR), limited proteolysis, and small-angle X-ray scattering (SAXS). The folded ensemble was characterized in detail in the presence of different urea concentrations by 1H-15N HSQC NMR. The {beta}-trefoil fold characteristic of native IL-1ra was preserved until the unfolding transition region beginning at 4 M urea. At the same time, a subset of native resonances disappeared gradually starting at low denaturant concentrations, indicating noncooperative changes in the folded state. Additional evidence of structural perturbations came frommore » the chemical shift analysis, nonuniform and bell-shaped peak intensity profiles, and limited proteolysis. In particular, the following nearby regions of the tertiary structure became progressively destabilized with increasing urea concentrations: the {beta}-hairpin interface of trefoils 1 and 2 and the H2a-H2 helical region. These regions underwent small-scale perturbations within the native baseline region in the absence of populated molten globule-like states. Similar regions were affected by elevated temperatures known to induce irreversible aggregation of IL-1ra. Further evidence of structural transitions invoking near-native conformations came from an optical spectroscopy analysis of its single-tryptophan variant W17A. The increase in the radius of gyration was associated with a single equilibrium unfolding transition in the case of two different denaturants, urea and guanidine hydrochloride (GuHCl). However, the compactness of urea- and GuHCl-unfolded molecules was comparable only at high denaturant concentrations and deviated under less denaturing conditions. Our results identified the role of conformational flexibility in IL-1ra aggregation and shed light on the nature of structural transitions within the folded ensembles of other {beta}-trefoil proteins, such as IL-1{beta} and hFGF-1.« less

Evaluation of inflammation during fixed orthodontic treatment.

PubMed

Bilgic, Fundagul; Akinci Sozer, Ozlem; Ozcan, Oguzhan; Gurpinar, Ahmet Burak; Yilmaz, Hakki; Ay, Yazgi

2016-11-01

The aim of this study was to assess effects of fixed orthodontic therapy on high-sensitivity C-reactive protein (hs-CRP) level, CBC parameters and levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), gamma glutamyl transferase (GGT), alkaline phosphatase (ALP), urea, creatinine, sodium (Na), potassium (K), calcium (Ca), total protein (TP), and albumin (Alb). Blood samples (7ml) were drawn at baseline, on days 1 and 7, and three months after placement of braces in the study group, while only one blood sample was drawn at baseline in the control group. Serum hs-CRP levels were measured by nephelometric method. Friedman two-way variance analysis was used to assess values with skewed distribution obtained at baseline, on days 1 and 7, in the third month. Wilcoxon rank sign test was performed if median values were unequal. During measurement periods, there were significant increases in hs-CRP level, WBC count and neutrophil count while a significant decrease in Na level (p<0.05). K level was significantly decreased on the day 1. No significant differences were detected in other biochemical parameters evaluated. Elevation in serum hs-CRP levels and neutrophil: lymphocyte ratio within first 3 months indicates that a systemic immune response develops against therapy in patients undergoing fixed orthodontic therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

Urea-induced ROS cause endothelial dysfunction in chronic renal failure.

PubMed

D'Apolito, Maria; Du, Xueliang; Pisanelli, Daniela; Pettoello-Mantovani, Massimo; Campanozzi, Angelo; Giacco, Ferdinando; Maffione, Angela Bruna; Colia, Anna Laura; Brownlee, Michael; Giardino, Ida

2015-04-01

The pathogenic events responsible for accelerated atherosclerosis in patients with chronic renal failure (CRF) are poorly understood. Here we investigate the hypothesis that concentrations of urea associated with CRF and increased ROS production in adipocytes might also increase ROS production directly in arterial endothelial cells, causing the same pathophysiologic changes seen with hyperglycemia. Primary cultures of human aortic endothelial cells (HAEC) were exposed to 20mM urea for 48 h. C57BL/6J wild-type mice underwent 5/6 nephrectomy or a sham operation. Randomized groups of 5/6 nephrectomized mice and their controls were also injected i.p. with a SOD/catalase mimetic (MnTBAP) for 15 days starting immediately after the final surgical procedure. Urea at concentrations seen in CRF induced mitochondrial ROS production in cultured HAEC. Urea-induced ROS caused the activation of endothelial pro-inflammatory pathways through the inhibition of GAPDH, including increased protein kinase C isoforms activity, increased hexosamine pathway activity, and accumulation of intracellular AGEs (advanced glycation end products). Urea-induced ROS directly inactivated the anti-atherosclerosis enzyme PGI2 synthase and also caused ER stress. Normalization of mitochondrial ROS production prevented each of these effects of urea. In uremic mice, treatment with MnTBAP prevented aortic oxidative stress, PGI2 synthase activity reduction and increased expression of the pro-inflammatory proteins TNFα, IL-6, VCAM1, Endoglin, and MCP-1. Taken together, these data show that urea itself, at levels common in patients with CRF, causes endothelial dysfunction and activation of proatherogenic pathways. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Antihyperglycemic Activity of Houttuynia cordata Thunb. in Streptozotocin-Induced Diabetic Rats

PubMed Central

Kumar, Manish; Prasad, Satyendra K.; Krishnamurthy, Sairam; Hemalatha, Siva

2014-01-01

Present study is an attempt to investigate plausible mechanism involved behind antidiabetic activity of standardized Houttuynia cordata Thunb. extract in streptozotocin-induced diabetic rats. The plant is used as a medicinal salad for lowering blood sugar level in North-Eastern parts of India. Oral administration of extract at 200 and 400 mg/kg dose level daily for 21 days showed a significant (P < 0.05) decrease in fasting plasma glucose and also elevated insulin level in streptozotocin-induced diabetic rats. It also significantly reversed all the alterations in biochemical parameters, that is, total lipid profile, blood urea, creatinine, protein, and antioxidant enzymes in liver, pancreas, and adipose tissue of diabetic rats. Furthermore, we have demonstrated that the extract significantly reversed the expression patterns of various glucose homeostatic enzyme genes like GLUT-2, GLUT-4, and caspase-3 levels but did not show any significant effect on PPAR-γ protein expressions. Additionally, the extract positively regulated mitochondrial membrane potential and succinate dehydrogenase (SDH) activity in diabetic rats. The findings justified the antidiabetic effect of H. cordata which is attributed to an upregulation of GLUT-4 and potential antioxidant activity, which may play beneficial role in resolving complication associated with diabetes. PMID:24707284

Serologic and hematologic values of wild coyotes in Wisconsin

USGS Publications Warehouse

Smith, G.J.; Rongstad, O.J.

1980-01-01

Blood samples were obtained from 30 coyotes (Canis latrans) captured in northern Wisconsin in conjunction with radio-telemetry studies. Samples were assayed for seven hematologic values, seven serum chemistries, serum albumin, globulin and total protein. Results are given with respect to sex and age and are compared with available data for captive wild and pen-raised coyotes. Leukocyte counts were greater for males than females and packed cell volumes were greater for adults than young, possibly due to differential response to capture and handling stress. Hemoglobin concentrations and calcium levels suggest differences in nutrition between pen-raised and wild coyotes. Sex and age differences in serum calcium for wild coyotes probably reflect nutritional differences between groups examined. Juvenile coyote serum alkaline phosphatase levels declined curvilinearly with age for coyotes less than one year old, suggesting a possible technique for separating juveniles and yearlings captured in autumn that are released for research purposes. Elevated glucose levels and leukocyte counts in wild coyotes may reflect greater handling stress than for pen-raised and captive coyotes. No significant sex or age effects were found for levels of serum urea nitrogen, total protein, cholesterol, and total bilirubin.

Renal function during pregnancy may predict risk of future hospitalization due to atherosclerotic-related morbidity.

PubMed

Wolak, Talya; Shoham-Vardi, Ilana; Sergienko, Ruslan; Sheiner, Eyal

2016-02-01

This study aims to examine whether renal function during pregnancy can serve as a surrogate marker for the risk of developing atherosclerotic-related morbidity. A case-control study, including women who gave birth at a tertiary referral medical centre during 2000-2012. This population was divided into cases of women who were subsequently hospitalized for atherosclerotic morbidity during the study period and age-matched controls. From the study population, we retrieved two groups: the creatinine (Cr) group: women who had at least one Cr measurement (4945 women) and the urea group: women who had at least one urea measurement (4932 women) during their pregnancies. In the Cr and urea group, there were 572 and 571 cases and 4373 and 4361 controls, respectively. The mean follow-up period in the Cr and urea group was 61.7 ± 37.0 and 57.3 ± 36.0 months, respectively. Cox proportional hazards models (controlling for confounders: gestational hypertension, gestational diabetes, obesity, maternal age, creatinine level (for urea), and gestational week) were used to estimate the adjusted hazard ratios (HR) for hospitalizations. A significant association was documented between renal function during pregnancy and long-term atherosclerotic morbidity. Multivariate analysis, showed that Cr at pregnancy index of ≥89 μmol/L was associated with a significant increased risk for hospitalization due to cardiovascular (CVS) events (adjusted HR = 2.91 CI 1.37-6.19 P = 0.005) and urea level ≤7 mmol/L was independently associated with reduced prevalence of CVS hospitalization (adjusted HR = 0.62 CI 0.57-0.86 P = 0.001). Renal function abnormality during pregnancy may reveal occult predisposition to atherosclerotic morbidity years after childbirth. © 2015 Asian Pacific Society of Nephrology.

Blood urea nitrogen/creatinine ratio identifies a high-risk but potentially reversible form of renal dysfunction in patients with decompensated heart failure.

PubMed

Brisco, Meredith A; Coca, Steven G; Chen, Jennifer; Owens, Anjali Tiku; McCauley, Brian D; Kimmel, Stephen E; Testani, Jeffrey M

2013-03-01

Identifying reversible renal dysfunction (RD) in the setting of heart failure is challenging. The goal of this study was to evaluate whether elevated admission blood urea nitrogen/creatinine ratio (BUN/Cr) could identify decompensated heart failure patients likely to experience improvement in renal function (IRF) with treatment. Consecutive hospitalizations with a discharge diagnosis of heart failure were reviewed. IRF was defined as ≥20% increase and worsening renal function as ≥20% decrease in estimated glomerular filtration rate. IRF occurred in 31% of the 896 patients meeting eligibility criteria. Higher admission BUN/Cr was associated with in-hospital IRF (odds ratio, 1.5 per 10 increase; 95% confidence interval [CI], 1.3-1.8; P<0.001), an association persisting after adjustment for baseline characteristics (odds ratio, 1.4; 95% CI, 1.1-1.8; P=0.004). However, higher admission BUN/Cr was also associated with post-discharge worsening renal function (odds ratio, 1.4; 95% CI, 1.1-1.8; P=0.011). Notably, in patients with an elevated admission BUN/Cr, the risk of death associated with RD (estimated glomerular filtration rate <45) was substantial (hazard ratio, 2.2; 95% CI, 1.6-3.1; P<0.001). However, in patients with a normal admission BUN/Cr, RD was not associated with increased mortality (hazard ratio, 1.2; 95% CI, 0.67-2.0; P=0.59; p interaction=0.03). An elevated admission BUN/Cr identifies decompensated patients with heart failure likely to experience IRF with treatment, providing proof of concept that reversible RD may be a discernible entity. However, this improvement seems to be largely transient, and RD, in the setting of an elevated BUN/Cr, remains strongly associated with death. Further research is warranted to develop strategies for the optimal detection and treatment of these high-risk patients.

Blood Urea Nitrogen/Creatinine Ratio Identifies a High-Risk but Potentially Reversible Form of Renal Dysfunction in Patients With Decompensated Heart Failure

PubMed Central

Brisco, Meredith A.; Coca, Steven G.; Chen, Jennifer; Owens, Anjali Tiku; McCauley, Brian D.; Kimmel, Stephen E.; Testani, Jeffrey M.

2014-01-01

Background Identifying reversible renal dysfunction (RD) in the setting of heart failure is challenging. The goal of this study was to evaluate whether elevated admission blood urea nitrogen/creatinine ratio (BUN/Cr) could identify decompensated heart failure patients likely to experience improvement in renal function (IRF) with treatment. Methods and Results Consecutive hospitalizations with a discharge diagnosis of heart failure were reviewed. IRF was defined as ≥20% increase and worsening renal function as ≥20% decrease in estimated glomerular filtration rate. IRF occurred in 31% of the 896 patients meeting eligibility criteria. Higher admission BUN/Cr was associated with inhospital IRF (odds ratio, 1.5 per 10 increase; 95% confidence interval [CI], 1.3–1.8; P<0.001), an association persisting after adjustment for baseline characteristics (odds ratio, 1.4; 95% CI, 1.1–1.8; P=0.004). However, higher admission BUN/Cr was also associated with post-discharge worsening renal function (odds ratio, 1.4; 95% CI, 1.1–1.8; P=0.011). Notably, in patients with an elevated admission BUN/Cr, the risk of death associated with RD (estimated glomerular filtration rate <45) was substantial (hazard ratio, 2.2; 95% CI, 1.6–3.1; P<0.001). However, in patients with a normal admission BUN/Cr, RD was not associated with increased mortality (hazard ratio, 1.2; 95% CI, 0.67–2.0; P=0.59; p interaction=0.03). Conclusions An elevated admission BUN/Cr identifies decompensated patients with heart failure likely to experience IRF with treatment, providing proof of concept that reversible RD may be a discernible entity. However, this improvement seems to be largely transient, and RD, in the setting of an elevated BUN/Cr, remains strongly associated with death. Further research is warranted to develop strategies for the optimal detection and treatment of these high-risk patients. PMID:23325460

Pharmacogenetic effects of angiotensin-converting enzyme inhibitors over age-related urea and creatinine variations in patients with dementia due to Alzheimer disease.

PubMed

Ferreira de Oliveira, Fabricio; Berretta, Juliana Marília; Suchi Chen, Elizabeth; Cardoso Smith, Marilia; Ferreira Bertolucci, Paulo Henrique

2016-06-30

Renal function declines according to age and vascular risk factors, whereas few data are available regarding genetically-mediated effects of anti-hypertensives over renal function. To estimate urea and creatinine variations in dementia due to Alzheimer disease (AD) by way of a pharmacogenetic analysis of the anti-hypertensive effects of angiotensin-converting enzyme inhibitors (ACEis). Consecutive outpatients older than 60 years-old with AD and no history of kidney transplant or dialytic therapy were recruited for prospective correlations regarding variations in fasting blood levels of urea and creatinine in one year, considering ACE genotypes of rs1800764 and rs4291 and their respective haplotypes, and treatment with ACEis along with blood pressure variations. For 190 patients, 152 had arterial hypertension, and 122 used ACEis. Minor allele frequencies were 0.492 for rs1800764-C and 0.337 for rs4291-T, both in Hardy-Weinberg equilibrium. There were no overall significant yearly variations in levels of urea and creatinine, but their concurrent variations were positively correlated (ρ <0.0001). Each A allele of rs4291 led to an yearly urea increase of 3,074 mg/dL, and an yearly creatinine increase of 0.044 mg/dL, while the use of ACEis was protective regarding creatinine variations. The use of ACEis was also protective for carriers of rs1800764-CT/rs4291-AA, while carriers of rs1800764-CT/rs4291-AT had steeper reductions in creatinine levels, particularly when they were treated with ACEis. Effects of ACEis over creatinine variations are genetically mediated and independent of blood pressure variations in older people with AD.

Pharmacogenetic effects of angiotensin-converting enzyme inhibitors over age-related urea and creatinine variations in patients with dementia due to Alzheimer disease

PubMed Central

Berretta, Juliana Marília; Suchi Chen, Elizabeth; Cardoso Smith, Marilia; Ferreira Bertolucci, Paulo Henrique

2016-01-01

Background: Renal function declines according to age and vascular risk factors, whereas few data are available regarding genetically-mediated effects of anti-hypertensives over renal function. Objective: To estimate urea and creatinine variations in dementia due to Alzheimer disease (AD) by way of a pharmacogenetic analysis of the anti-hypertensive effects of angiotensin-converting enzyme inhibitors (ACEis). Methods: Consecutive outpatients older than 60 years-old with AD and no history of kidney transplant or dialytic therapy were recruited for prospective correlations regarding variations in fasting blood levels of urea and creatinine in one year, considering ACE genotypes of rs1800764 and rs4291 and their respective haplotypes, and treatment with ACEis along with blood pressure variations. Results: For 190 patients, 152 had arterial hypertension, and 122 used ACEis. Minor allele frequencies were 0.492 for rs1800764-C and 0.337 for rs4291-T, both in Hardy-Weinberg equilibrium. There were no overall significant yearly variations in levels of urea and creatinine, but their concurrent variations were positively correlated (ρ <0.0001). Each A allele of rs4291 led to an yearly urea increase of 3,074 mg/dL, and an yearly creatinine increase of 0.044 mg/dL, while the use of ACEis was protective regarding creatinine variations. The use of ACEis was also protective for carriers of rs1800764-CT/rs4291-AA, while carriers of rs1800764-CT/rs4291-AT had steeper reductions in creatinine levels, particularly when they were treated with ACEis. Conclusions: Effects of ACEis over creatinine variations are genetically mediated and independent of blood pressure variations in older people with AD. PMID:27546928

Prediction of ammonia emission from dairy cattle manure based on milk urea nitrogen: relation of milk urea nitrogen to urine urea nitrogen excretion.

PubMed

Burgos, S A; Fadel, J G; Depeters, E J

2007-12-01

The objectives of this study were to assess the relationship between urinary urea N (UUN) excretion (g/d) and milk urea N (MUN; mg/dL) and to test whether the relationship was affected by stage of lactation and the dietary crude protein (CP) content. Twelve lactating multiparous Holstein cows were randomly selected and blocked into 3 groups of 4 cows intended to represent early [123 +/- 26 d in milk (DIM); mean +/- standard deviation], mid (175 +/- 3 DIM), and late (221 +/- 12 DIM) lactation stages. Cows within each stage of lactation were randomly assigned to a treatment sequence within a split-plot Latin square balanced for carryover effects. Stage of lactation formed the main plots (squares) and dietary CP levels (15, 17, 19, and 21% of diet dry matter) formed the subplots. Graded amounts of urea were added to the basal total mixed ration to linearly increase dietary CP content while maintaining similar concentrations of all other nutrients among treatments. The experimental periods lasted 7 d, with d 1 to 6 used for adjustment to diets and d 7 used for total collection of urine as well as milk and blood sample collection. Dry matter intake and yields of milk, fat, protein, and lactose declined progressively with lactation stage and were unaffected by dietary CP content. Milk and plasma urea-N as well as UUN concentration and excretion increased in response to dietary CP content. Milk and urine urea-N concentration rose at increasing and decreasing rates, respectively, as a function of plasma urea-N. The renal urea-N clearance rate differed among lactation stages and dietary CP contents. The relationship between UUN excretion and MUN differed among lactation stages and diverged from linearity for cows in early and late lactation. However, these differences were restricted to very high MUN concentrations. Milk urea N may be a useful tool to predict the UUN excretion and ultimately NH(3) emission from dairy cattle manure.

Antidiabetic activity of aqueous extract and non polysaccharide fraction of Cynodon dactylon Pers.

PubMed

Jarald, E E; Joshi, S B; Jain, D C

2008-09-01

Petroleum ether (60 degrees-80 degrees C), chloroform, acetone, ethanol, aqueous and crude hot water extracts of the whole plant of C. dactylon and the two fractions of aqueous extract were tested for antihyperglycaemic activity in glucose overloaded hyperglycemic rats and in alloxan induced diabetic model at two-dose levels, 200 and 400 mg/kg (po) respectively. The aqueous extract of C. dactylon and the non polysaccharide fraction of aqueous extract were found to exhibit significant antihyperglycaemic activity and only the non polysaccharide fraction was found to produce hypoglycemia in fasted normal rats. Treatment of diabetic rats with aqueous extract and non polysaccharide fraction of the plant decreased the elevated biochemical parameters, glucose, urea, creatinine, serum cholesterol, serum triglyceride, high density lipoprotein, low density lipoprotein, haemoglobin and glycosylated haemoglobin significantly. Comparatively, the non polysaccharide fraction of aqueous extract was found to be more effective than the aqueous extract.

Long-Term Outcomes in a Family with Nephrogenic Syndrome of Inappropriate Antidiuresis

PubMed Central

Cho, Yoon Hi; Gitelman, Stephen; Rosenthal, Stephen; Ambler, Geoffrey

2009-01-01

We report a familial case of the nephrogenic syndrome of inappropriate antidiuresis (NSIAD), including 30-year followup data on two patients. The proband and one maternal uncle presented in their infancy with severe recurrent hyponatremia, and clinical pictures consistent with the syndrome of inappropriate antidiuretic hormone (SIADH) in the absence of an elevated ADH level. They were both confirmed to be hemizygous for the R137C mutation on the V2R gene (AVPR2), the same locus of the gain of function mutation demonstrated in the original reports of this condition. The proband's mother was identified as an asymptomatic carrier of this X-linked condition. Our case describes a favourable long-term outcome for NSIAD, in particular, successful treatment with oral urea during the infancy period, and with self-regulated precautions on fluid intake into adult life. PMID:20148077

Long-lasting ovulation inhibition with a new injectable progestagen ORG-2154.

PubMed

Coutinho, E M; De Souza, J C; Barbosa, I C; Dourado Silva, V

1982-06-01

A new long-acting injectable progestagen was tested in 15 women who volunteered for the study. The occurrence of ovulation was assumed by the elevation of progesterone levels above 2ng/ml following a pre-ovulatory estradiol peak. Following a 200mg injection, ovulation was inhibited in all 15 women for five to ten months. In four subjects the interval between the injection and the first progesterone peak was five months. For eight, the interval was six to eight months. In the other three women, ovulation occurred more than eight months following injection. Bleeding episodes, similar to menstruation, occurred in most patients. Bleeding intervals lasting longer than 45 days occurred in nine subjects but more prolonged amenorrhea lasting longer than 60 days was reported by only five subjects. Blood chemistry which included blood cell counts, cholesterol, glucose, alkaline phosphatase, transaminases, urea nitrogen and creatinine remained within normal limits throughout the treatment.

Myogenic expression of an injectable protease-resistant growth hormone-releasing hormone augments long-term growth in pigs

NASA Technical Reports Server (NTRS)

Draghia-Akli, R.; Fiorotto, M. L.; Hill, L. A.; Malone, P. B.; Deaver, D. R.; Schwartz, R. J.

1999-01-01

Ectopic expression of a new serum protease-resistant porcine growth hormone-releasing hormone, directed by an injectable muscle-specific synthetic promoter plasmid vector (pSP-HV-GHRH), elicits growth in pigs. A single 10 mg intramuscular injection of pSP-HV-GHRH DNA followed by electroporation in three-week-old piglets elevated serum GHRH levels by twofold to fourfold, enhanced growth hormone secretion, and increased serum insulin-like growth factor-I by threefold to sixfold over control pigs. After 65 days the average body weight of the pigs injected with pSP-HV-GHRH was approximately 37% greater than the placebo-injected controls and resulted in a significant reduction in serum urea concentration, indicating a decrease in amino acid catabolism. Evaluation of body composition indicated a uniform increase in mass, with no organomegaly or associated pathology.

Association of plasma manganese levels with chronic renal failure.

PubMed

Sánchez-González, Cristina; López-Chaves, Carlos; Gómez-Aracena, Jorge; Galindo, Pilar; Aranda, Pilar; Llopis, Juan

2015-01-01

Manganese (Mn) is an essential trace element involved in the formation of bone and in amino acid, lipid and carbohydrate metabolism. Mn excess may be neurotoxic to humans, affecting specific areas of the central nervous system. However, relatively little is known about its physiological and/or toxicological effects, and very few data are available concerning the role of Mn in chronic renal failure (CRF). This paper describes a 12-month study of the evolution of plasma Mn levels in predialysis patients with CRF and the relationship with energy and macronutrient intake. The participants in this trial were 64 patients with CRF in predialysis and 62 healthy controls. Plasma levels of creatinine, urea, uric acid, total protein and Mn were measured. The glomerular filtration rate (GFR) was calculated using the Cockcroft-Gault index. The CRF patients had higher plasma levels of creatinine, urea, uric acid and Mn and a lower GFR than the controls. Plasma Mn was positively correlated with creatinine, plasma urea and plasma uric acid and was negatively correlated with the GFR and the intake of energy and macronutrients. In conclusion, CRF in predialysis patients is associated with increases in circulating levels of Mn. Copyright © 2015 Elsevier GmbH. All rights reserved.

Short term responses of nitrogen trace gas emissions to nitrogen fertilization in tropical sugar cane: Variations due to soils and management practices

NASA Technical Reports Server (NTRS)

Matson, P. A.; Billow, C.; Hall, S.; Zachariassen, J.

1994-01-01

Nitrogen (N) fertilization of agricultural systems is thought to be a major source of the increase in atmospheric N2O; NO emissions from soils have also been shown to increase due to N fertilization. While N fertilizer use is increasing rapidly in the developing world and in the tropics, nearly all of our information on gas emissions is derived from studies of temperate zone agriculture. Using chambers, we measured fluxes of N2O and NO following urea fertilization in tropical sugar cane systems growing on a variety of soil types in the Hawaiian Islands, USA. On the island of Maui, where urea is applied in irrigation lines and soils are mollisols and inceptisols, N2O fluxes were elevated for a week or less following fertilization; maximum average fluxes were typically less than 30 ng cm(exp -2)/ h. NO fluxes were often an order of magnitude less than N2O. Together, N2O and NO represented from 0.01 - 0.5% of the applied N. In fields on the island of Hawaii, where urea is broadcast on the surface and soils are andisols, N2O fluxes were similar in magnitude to Maui but remained elevated for much longer periods after fertilization. NO emissions were 2-5 times higher than N2O through most of the sampling periods. Together the gases loss represented approximately 1. 1 - 3% of the applied N. Laboratory studies indicate that denitrification is a critical source of N2O in Maui, but that nitrification is more important in Hawaii. Experimental studies suggest that differences in the pattern of N2O/NO and the processes producing them are a result of both carbon availability and placement of fertilizer, and that the more information-intensive fertilizer management practice results in lower emissions.

Watershed level examination of urea fate and transport and the production of the biotoxin domoic acid

USDA-ARS?s Scientific Manuscript database

The Chesapeake Bay, the largest estuary in the world, is an important source of many fish and shellfish. The safety of these species as a food source is currently at risk due to nutrient pollution. Urea, a form of organic nitrogen found in manure and fertilizer, is increasing in usage within the Ba...

Stream chemistry following a forest fire and urea fertilization in north-central Washington.

Treesearch

Arthur R. Tiedemann

1973-01-01

During 2 years of study, nitrate-N in streamflow increased from background levels of 0.005 part per million (p.p.m.) in a control stream to 0.042 and 0.310 p.p.m. in streams from burned and burned, urea-fertilized watersheds, respectively. Cation concentration increased on the burned, unfertilized watershed, but because of dilution effects,...

Trimethylamine N-Oxide: The Good, the Bad and the Unknown.

PubMed

Velasquez, Manuel T; Ramezani, Ali; Manal, Alotaibi; Raj, Dominic S

2016-11-08

Trimethylamine N -oxide (TMAO) is a small colorless amine oxide generated from choline, betaine, and carnitine by gut microbial metabolism. It accumulates in the tissue of marine animals in high concentrations and protects against the protein-destabilizing effects of urea. Plasma level of TMAO is determined by a number of factors including diet, gut microbial flora and liver flavin monooxygenase activity. In humans, a positive correlation between elevated plasma levels of TMAO and an increased risk for major adverse cardiovascular events and death is reported. The atherogenic effect of TMAO is attributed to alterations in cholesterol and bile acid metabolism, activation of inflammatory pathways and promotion foam cell formation. TMAO levels increase with decreasing levels of kidney function and is associated with mortality in patients with chronic kidney disease. A number of therapeutic strategies are being explored to reduce TMAO levels, including use of oral broad spectrum antibiotics, promoting the growth of bacteria that utilize TMAO as substrate and the development of target-specific molecules with varying level of success. Despite the accumulating evidence, it is questioned whether TMAO is the mediator of a bystander in the disease process. Thus, it is important to undertake studies examining the cellular signaling in physiology and pathological states in order to establish the role of TMAO in health and disease in humans.

Binding of urea and thiourea with a barbiturate derivative: experimental and theoretical approach.

PubMed

Dixit, Namrata; Shukla, P K; Mishra, P C; Mishra, Lallan; Roesky, Herbert W

2010-01-14

A barbiturate derivative [1,5-dihydro-5-[5-pyrimidine-2,4(1H,3H)-dionyl]-2H-chromeno[2,3-d] pyrimidine-2,4(3H)-dione)] (L1) possesses functionalities complementary to amide and thioamide. Hence its binding with urea and thiourea, is monitored using UV-vis and fluorescence titrations as well as isothermal titration calorimetry (ITC) study. Theoretical studies on hydrogen-bonded complexes of L1-urea and L1-thiourea in the gas phase, aqueous, and DMSO medium are carried out using density functional theory (DFT) at the B3LYP/6-31G** level. The theoretical calculations support the experimental results.

Nitrogen metabolism in tambaqui (Colossoma macropomum), a neotropical model teleost: hypoxia, temperature, exercise, feeding, fasting, and high environmental ammonia.

PubMed

Wood, Chris M; de Souza Netto, José Gadelha; Wilson, Jonathan M; Duarte, Rafael M; Val, Adalberto Luis

2017-01-01

The total rate of N-waste excretion (M N ) in juvenile tambaqui living in ion-poor Amazonian water comprised 85 % ammonia-N (M Amm-N ) and 15 % urea-N (M Urea-N ). Both occurred mainly across the gills with only ~5 % of M Amm-N and ~39 % of M Urea-N via the urine. Tambaqui were not especially tolerant to high environmental ammonia (HEA), despite their great resistance to other environmental factors. Nevertheless, they were able to maintain a continued elevation of M Amm-N during and after 48-h exposure to 2.5 mmol L -1 HEA. The normally negative transepithelial potential (-18 mV) increased to -9 mV during the HEA period, which would help to reduce branchial NH 4 + entry. During 3 h of acute environmental hypoxia (30 % saturation), M Amm-N declined, and recovered thereafter, similar to the response seen in other hypoxia-tolerant teleosts; M Urea-N did not change. However, during gradual hypoxia, M Amm-N remained constant, but M Urea-N eventually fell. The acute temperature sensitivities of M Amm-N and M N were low from 28 °C (acclimation) to 33 °C (Q10 ~1.5), but high (~3.8) from 33 to 38 °C, relative to [Formula: see text] (~1.9 throughout). In contrast, M Urea-N exhibited a different pattern over these temperature ranges (Q10 2.6 and 2.1, respectively). The nitrogen quotient (NQ = 0.16-0.23) was high at all temperatures, indicating a 60-85 % reliance on protein to fuel aerobic metabolism in these fasting animals. During steady-state aerobic exercise, [Formula: see text] and M Urea-N increased in parallel with velocity (up to 3.45 body lengths s -1 ), but M Amm (and thus M N ) remained approximately constant. Therefore, the NQ fell progressively, indicating a decreasing reliance on protein-based fuels, as work load increased. In group feeding trials using 45 % protein commercial pellets, tambaqui excreted 82 % (range 39-170 %) of the dietary N within 24 h; N-retention efficiency was inversely related to the ration voluntarily consumed. M Amm-N peaked at 4-6 h, and M Urea-N at 6-9-h post-feeding, with an additional peak in M Amm-N only at 21 h. During subsequent fasting, M N stabilized at a high endogenous rate from 2 through 8 days post-feeding. Possible reasons for the high wasting of protein-N during both fasting and feeding are discussed.

Symplocos cochinchinensis attenuates streptozotocin-diabetes induced pathophysiological alterations of liver, kidney, pancreas and eye lens in rats.

PubMed

Antu, Kalathookunnel Antony; Riya, Mariam Philip; Mishra, Arvind; Sharma, Sharad; Srivastava, Arvind K; Raghu, Kozhiparambil Gopalan

2014-09-01

The beneficial effects of hydroethanol extract of Symplocos cochinchinensis (SCE) has been explored against hyperglycemia associated secondary complications in streptozotocin induced diabetic rat model. The experimental groups consist of normal control (NC), diabetic control (DC), DC + metformin 100 mg kg(-1) bwd, DC + SCE 250 and DC + SCE 500. SCEs and metformin were administered daily for 21 days and sacrificed on day 22. Oral glucose tolerance test, plasma insulin, % HbA1c, urea, creatinine, aspartate aminotransferase, alanine aminotransferase, albumin, total protein etc. were analysed. Aldose reductase (AR) activity in the eye lens was also checked. On day 21, DC rats showed significantly abnormal glucose response, HOMA-IR, % HbA1c, decreased activity of antioxidant enzymes and GSH, elevated AR activity, hepatic and renal oxidative stress markers like malondialdehyde, protein carbonyls compared to NC. DC rats also exhibited increased level of plasma urea and creatinine. Treatment with SCE protected from the deleterious alterations of biochemical parameters in a dose dependent manner including histopathological alterations in pancreas. SCE 500 exhibited 46.28% of glucose lowering effect and decreased HOMA-IR (2.47), % HbA1c (6.61), lens AR activity (15.99%), and hepatic, renal oxidative stress and function markers compared to DC group. Considerable amount of liver and muscle glycogen was replenished by SCE treatment in diabetic animals. Although metformin showed better effect, the activity of SCE was very much comparable with this drug. Copyright © 2014 Elsevier GmbH. All rights reserved.

Risk Stratification of Acute Kidney Injury Using the Blood Urea Nitrogen/Creatinine Ratio in Patients With Acute Decompensated Heart Failure.

PubMed

Takaya, Yoichi; Yoshihara, Fumiki; Yokoyama, Hiroyuki; Kanzaki, Hideaki; Kitakaze, Masafumi; Goto, Yoichi; Anzai, Toshihisa; Yasuda, Satoshi; Ogawa, Hisao; Kawano, Yuhei

2015-01-01

Risk stratification of acute kidney injury (AKI) is important for acute decompensated heart failure (ADHF). The aim of this study was to determine whether clinical markers, such as the blood urea nitrogen/creatinine ratio (BUN/Cr) or BUN or creatinine values alone, stratify the risk of AKI for mortality. In all, 371 consecutive ADHF patients were enrolled in the study. AKI was defined as serum creatinine ≥0.3 mg/dl or a 1.5-fold increase in serum creatinine levels within 48 h. During ADHF therapy, AKI occurred in 99 patients; 55 patients died during the 12-month follow-up period. Grouping patients according to AKI and a median BUN/Cr at admission of 22.1 (non-AKI+low BUN/Cr, non-AKI+high BUN/Cr, AKI+low BUN/Cr, and AKI+high BUN/Cr groups) revealed higher mortality in the AKI+high BUN/Cr group (log-rank test, P<0.001). Cox's proportional hazard analysis revealed an association between AKI+high BUN/Cr and mortality, whereas the association with AKI+low BUN/Cr did not reach statistical significance. When patients were grouped according to AKI and median BUN or creatinine values at admission, AKI was associated with mortality, regardless of BUN or creatinine. The combination of AKI and elevated BUN/Cr, but not BUN or creatinine individually, is linked with an increased risk of mortality in ADHF patients, suggesting that the BUN/Cr is useful for risk stratification of AKI.

Investigation of the Antifatigue Effects of Korean Ginseng on Professional Athletes by Gas Chromatography-Time-of-Flight-Mass Spectrometry-Based Metabolomics.

PubMed

Yan, Bei; Liu, Yao; Shi, Aixin; Wang, Zhihong; Aa, Jiye; Huang, Xiaoping; Liu, Yi

2018-05-01

Ginseng is usually used for alleviating fatigue. The purpose of this paper was to evaluate the regulatory effect of Korean ginseng on the metabolic pattern in professional athletes, and, further, to explore the underlying mechanism of the antifatigue effect of Korean ginseng. GC-time-of-flight-MS was used to profile serum samples from professional athletes before training and after 15 and 30 day training, and professional athletes administered with Korean ginseng in the meanwhile. Biochemical parameters of all athletes were also analyzed. For the athlete control group, strength-endurance training resulted in an elevation of creatine kinase (CK) and blood urea nitrogen (BUN), and a reduction in blood hemoglobin, and a dynamic trajectory of the metabolomic profile which were related to fatigue. Korean ginseng treatment not only lead to a marked reduction in CK and blood urea nitrogen (BUN) in serum, but also showed regulatory effects on the serum metabolic profile and restored scores plots close to normal, suggesting that the change in metabolic profiling could reflect the antifatigue effect of Korean ginseng. Furthermore, perturbed levels of 11 endogenous metabolites were regulated by Korean ginseng significantly, which might be primarily involved in lipid metabolism, energy balance, and chemical signaling. These findings suggest that metabolomics is a potential tool for the evaluation of the antifatigue effect of Korean ginseng and for the elucidation of its pharmacological mechanism.

Recurrent somnolence in a 17-month-old infant: late-onset ornithine transcarbamylase (OTC) deficiency due to the novel hemizygous mutation c.535C > T (p.Leu179Phe).

PubMed

Fantur, Michaela; Karall, Daniela; Scholl-Buergi, Sabine; Häberle, Johannes; Rauchenzauner, Markus; Fruehwirth, Martin

2013-01-01

Herein, we describe a case of a now 28-month-old boy who presented at the age of 17 months with four episodes of recurrent vomiting and somnolence during a period of four months with increasing severity. A comprehensive clinical and metabolic evaluation revealed normal blood pH and blood glucose, normal cerebral computed tomography and electroencephalogram but an elevated plasma ammonia concentration, which raised the suspicion of a urea cycle disorder. The combination of elevated urinary orotic acid and plasma glutamine with normal citrulline suggested the diagnosis of ornithine transcarbamylase (OTC) deficiency, which was confirmed by molecular genetic testing revealing the novel hemizygous mutation c.535C > T (p.Leu179Phe) of the OTC gene. After restitution of anabolism by administration of parenteral glucose, substitution of citrulline and detoxification of ammonia with sodium benzoate, the patient recovered rapidly and is in a stable metabolic and neurological state since then. This case underlines that the diagnosis of a urea cycle defect should be considered in the differential diagnosis of recurrent idiopathic vomiting in combination with unexplained neurological symptoms also beyond the neonatal period due to the possibility of mild or atypical late-onset presentation (e.g. OTC deficiency in hemizygous males). Copyright © 2012 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

[The effect of vegetarian diet on selected biochemical and blood morphology parameters].

PubMed

Nazarewicz, Rafał

2007-01-01

The objective was to examine whether vegetarian diet influence biochemical parameters of blood and plasma urea in selective vegetarian group. The investigation covered 41 subject, 22 of them had been applying vegetarian diet and 19 were omnivorous. The study shows statistically significant lower values of white blood cells, % and amounts of neutrocytes and insignificant lower level of red blood cells, hemoglobine, hematocrit and platelet in vegetarian group. Significant lower plasma urea level was observed in that group. These changes indicate that high quality deficiency protein was due to vegetarian diet.

Technical note: Nitrogen isotopic fractionation can be used to predict nitrogen-use efficiency in dairy cows fed temperate pasture.

PubMed

Cheng, L; Sheahan, A J; Gibbs, S J; Rius, A G; Kay, J K; Meier, S; Edwards, G R; Dewhurst, R J; Roche, J R

2013-12-01

The objective of this study was to investigate the relationship between nitrogen isotopic fractionation (δ(15)N) and nitrogen-use efficiency (milk nitrogen/nitrogen intake; NUE) in pasture-fed dairy cows supplemented with increasing levels of urea to mimic high rumen degradable protein pastures in spring. Fifteen cows were randomly assigned to freshly cut pasture and either supplemented with 0, 250, or 336 g urea/d. Feed, milk, and plasma were analyzed for δ(15)N, milk and plasma for urea nitrogen concentration, and plasma for ammonia concentration. Treatment effects were tested using ANOVA and relationships between variables were established by linear regression. Lower dry matter intake (P = 0.002) and milk yield (P = 0.002) occurred with the highest urea supplementation (336 g urea/d) compared with the other two treatments. There was a strong linear relationship between milk δ(15)N - feed δ(15)N and NUE: [NUE (%) = 58.9 - 10.17 × milk δ(15)N - feed δ(15)N (‰) (r(2) = 0.83, P < 0.001, SE = 1.67)] and between plasma δ(15)N - feed δ(15)N and NUE: [NUE (%) = 52.4 - 8.61 × plasma δ(15)N - feed δ(15)N (‰) (r(2) = 0.85, P < 0.001, SE = 1.56)] . This study confirmed the potential use of δ(15)N to predict NUE in cows consuming different levels of rumen degradable protein.

Differential modulation of ammonia excretion, Rhesus glycoproteins and ion-regulation in common carp (Cyprinus carpio) following individual and combined exposure to waterborne copper and ammonia.

PubMed

Sinha, Amit Kumar; Kapotwe, Mumba; Dabi, Shambel Boki; Montes, Caroline da Silva; Shrivastava, Jyotsna; Blust, Ronny; De Boeck, Gudrun

2016-01-01

The main objective of this study was to understand the mode of interaction between waterborne copper (Cu) and high environmental ammonia (HEA) exposure on freshwater fish, and how they influence the toxicity of each other when present together. For this purpose, individual and combined effects of Cu and HEA were examined on selected physiological and ion-regulatory processes and changes at transcript level in the common carp (Cyprinus carpio). Juvenile carp were exposed to 2.6μM Cu (25% of the 96h LC50value) and to 0.65mM ammonia (25% of the 96h LC50value) singly and as a mixture for 12h, 24h, 48h, 84h and 180h. Responses such as ammonia (Jamm) and urea (Jurea) excretion rate, plasma ammonia and urea, plasma ions (Na(+), Cl(-) and K(+)), muscle water content (MWC) as well as branchial Na(+)/K(+)-ATPase (NKA) and H(+)-ATPase activity, and branchial mRNA expression of NKA, H(+)-ATPase, Na(+)/H(+) exchanger (NHE-3) and Rhesus (Rh) glycoproteins were investigated under experimental conditions. Results show that Jamm was inhibited during Cu exposure, while HEA exposed fish were able to increase excretion efficiently. In the combined exposure, Jamm remained at the control levels indicating that Cu and HEA abolished each other's effect. Expression of Rhcg (Rhcg-a and Rhcg-b) mRNA was upregulated during HEA, thereby facilitated ammonia efflux out of gills. On the contrary, Rhcg-a transcript level declined following Cu exposure which might account for Cu induced Jamm inhibition. Likewise, Rhcg-a was also down-regulated in Cu-HEA co-exposed fish whilst a temporary increment was noted for Rhch-b. Fish exposed to HEA displayed pronounced up-regulation in NKA expression and activity and stable plasma ion levels. In both the Cu exposure alone and combined Cu-HEA exposure, ion-osmo homeostasis was adversely affected, exemplified by the significant reduction in plasma [Na(+)] and [Cl(-)], and elevated plasma [K(+)], along with an elevation in MWC. These changes were accompanied by a decline in NKA activity. Gill H(+)-ATPase mRNA levels and activities were not affected by either Cu or HEA or both. Likewise, NHE-3 expression remained unaltered but tended to be numerically higher during HEA exposure. Overall, these data suggest that at equitoxic concentrations (25% of 96h LC50), the individual effect of Cu is more harmful while HEA induces quicker adaptive responses. Our findings also denote a competitive mode of interaction, exemplified by the inhibition of HEA -mediated adaptive responses in the presence of Cu. Copyright © 2015 Elsevier B.V. All rights reserved.

Antiurolithiatic Effect of Sirupeelai Samoola Kudineer: A Polyherbal Siddha Decoction on Ethylene Glycol-induced Renal Calculus in Experimental Rats

PubMed Central

Vasanthi, A. Hannah Rachel; Muthulakshmi, V.; Gayathri, V.; Manikandan, R.; Ananthi, S.; Kuruvilla, Sarah

2017-01-01

Background: Sirupeelai Samoola Kudineer (SK), a polyherbal decoction containing four medicinal plants has been used in Siddha system of medicine, practiced in Southern parts of India for the management of urolithiasis. Objective: The present study is carried out to scientifically validate the traditional claim and to study the mechanism of action of the drug. Materials and Methods: In the present study, anti-urolithiatic effect of SK was evaluated in Sprague-Dawley rats using ethylene glycol through drinking water and intraperitoneal injection of sodium oxalate. Renal damage was confirmed by the increased production of thiobarbituric acid reactive substance (TBARS). Results: Co-treatment with SK to urolithiatic rats for 21 days significantly prevented the elevation of renal and urinary stone biomarkers in plasma and renal tissue thereby preventing renal damage and the formation of renal calculi. Administration of SK at all doses and cystone restored the antioxidant (glutathione) levels by preventing the elevation of TBARS in the kidney tissue, which was further confirmed by histological sections. Conclusions: SK treatment promotes diuresis which leads to flushing of the renal stones and maintains the alkaline environment in the urinary system which probably mediates the antilithiatic activity. SK provides structural and functional protection to the kidneys by enhancing its physiological function against stone formation and validates its clinical use. SUMMARY SK exhibited antilithiatic and diuretic potential in ethylene glycol and sodium oxalate induced urolithiasis in ratsElevated urinary stone markers (Calcium, oxalate, uric acid, magnesium and phosphates) in plasma and renal tubular enzymes (LDH, GGT, ALP, AST ALT) in urolithiatic rats were reversed by SK treatmentSK administration significantly reduced the level of renal stress markers like Urea, Creatinine, LPO and elevated SOD, GPx, GSH levels aiding in nephroprotectionSK also provides structural and functional protection against ethylene glycol- induced renal calculus in rats as evidenced by histopathological studies. Abbreviations used: SK: Sirupeelai Samoola Kudineer; TBARS: ThioBarbituric Acid Reactive Substances; SOD: SuperOxide Dismutase; GPx: Gluthathione peroxidase; GSH- Glutathione; LPO: Lipid peroxidation as measured as TBARS; AST: Aspartate AminoTransferase; ALT: Alanine Amino transferase; GGT: Gamma Glutamyl Transferase; LDH: Lactate Dehydrogenase. PMID:28808392

Sensitivity of the spiny dogfish (Squalus acanthias) to waterborne silver exposure.

PubMed

De Boeck, G; Grosell, M; Wood, C

2001-10-01

The physiological effects of waterborne silver exposure (added as AgNO(3)) on spiny dogfish, Squalus acanthias, were evaluated at 30, 200 and 685 microg silver per l in 30 per thousand seawater. These concentrations cover the toxic range observed for freshwater teleosts, where silver is extremely toxic, to seawater teleosts which tolerate higher silver concentrations. However, these levels are considerably higher than those that occur in the normal environment. At 685 microg l(-1), dogfish died within 24 h. Causes of death were respiratory as well as osmoregulatory failure. Arterial P(a)O(2) rapidly declined below 20 Torr, and blood acidosis (both respiratory and metabolic) occurred. Urea excretion increased dramatically and plasma urea dropped from 340 to 225 mM. There were pronounced increases in plasma Na(+), Cl(-), and Mg(2+), indicative of ionoregulatory failure due to increased diffusive permeability as well as inhibited NaCl excretion. At 200 microg l(-1), fish died between 24 and 72 h of silver exposure. The same physiological events occurred with a small time delay. At 30 microg l(-1), effects were much less severe, although slight mortality (12.5%) still occurred. Respiratory alkalosis occurred, together with moderate elevations in plasma Na(+) and Cl(-) levels. Silver accumulated to the highest concentrations on gills, with only low levels in the intestine, in accord with the virtual absence of drinking. Na(+)/K(+)-ATP-ase activities of gill and rectal gland tissue were impaired at the highest silver concentration. Normal gill function was impaired due to swelling and fusion of lamellae, lamellar aneurism and lifting of the lamellar epithelium. Our results clearly indicate that this elasmobranch is much more sensitive (about 10-fold) to silver than marine teleosts, with silver's toxic action exerted on the gill rather than on the intestine, in contrast to the latter.

Relationships between Circulating Urea Concentrations and Endometrial Function in Postpartum Dairy Cows.

PubMed

Cheng, Zhangrui; Oguejiofor, Chike F; Swangchan-Uthai, Theerawat; Carr, Susan; Wathes, D Claire

2015-08-14

Both high and low circulating urea concentrations, a product of protein metabolism, are associated with decreased fertility in dairy cows through poorly defined mechanisms. The rate of involution and the endometrial ability to mount an adequate innate immune response after calving are both critical for subsequent fertility. Study 1 used microarray analysis to identify genes whose endometrial expression 2 weeks postpartum correlated significantly with the mean plasma urea per cow, ranging from 3.2 to 6.6 mmol/L. The biological functions of 781 mapped genes were analysed using Ingenuity Pathway Analysis. These were predominantly associated with tissue turnover (e.g., BRINP1, FOXG1), immune function (e.g., IL17RB, CRISPLD2), inflammation (e.g., C3, SERPINF1, SERPINF2) and lipid metabolism (e.g., SCAP, ACBD5, SLC10A). Study 2 investigated the relationship between urea concentration and expression of 6 candidate genes (S100A8, HSP5A, IGF1R, IL17RB, BRINP1, CRISPLD2) in bovine endometrial cell culture. These were treated with 0, 2.5, 5.0 or 7.5 mmol/L urea, equivalent to low, medium and high circulating values with or without challenge by bacterial lipopolysaccharide (LPS). LPS increased S100A8 expression as expected but urea treatment had no effect on expression of any tested gene. Examination of the genes/pathways involved suggests that plasma urea levels may reflect variations in lipid metabolism. Our results suggest that it is the effects of lipid metabolism rather than the urea concentration which probably alter the rate of involution and innate immune response, in turn influencing subsequent fertility.

Effects of dietary fibre and protein on urea transport across the cecal mucosa of piglets.

PubMed

Stumpff, F; Lodemann, U; Van Kessel, A G; Pieper, R; Klingspor, S; Wolf, K; Martens, H; Zentek, J; Aschenbach, J R

2013-12-01

In ruminants, gastrointestinal recycling of urea is acutely enhanced by fibre-rich diets that lead to high ruminal concentration of short chain fatty acids (SCFA), while high ammonia has inhibitory effects. This study attempted to clarify if urea flux to the porcine cecum is similarly regulated. Thirty-two weaned piglets were fed diets containing protein (P) of poor prececal digestibility and fibre (F) at high (H) or low levels (L) in a 2 × 2 factorial design. After slaughter, cecal content was analyzed and the cecal mucosa incubated in Ussing chambers to measure the effect of pH, SCFA and NH4 (+) on the flux rates of urea, short-circuit current (I sc) and tissue conductance (G t). NH4 (+) significantly enhanced I sc (from 0.5 ± 0.2 to 1.2 ± 0.1 μEq cm(-2) h(-1)). No acute effects of SCFA or ammonia on urea flux were observed. Tissue conductance was significantly lower in the high dietary fibre groups irrespective of the protein content. Only the HP-LF group emerged as different from all others in terms of urea flux (74 ± 6 versus 53 ± 3 nmol cm(-2) h(-1)), associated with higher cecal ammonia concentration and reduced fecal consistency. The data suggest that as in the rumen, uptake of ammonia by the cecum may involve electrogenic transport of the ionic form (NH4 (+)). In contrast to findings in the rumen, neither a high fibre diet nor acute addition of SCFA enhanced urea transport across the pig cecum. Instead, a HP-LF diet had stimulatory effects. A potential role for urea recycling in stabilizing luminal pH is discussed.

Light exposure enhances urea absorption in the fluted giant clam, Tridacna squamosa, and up-regulates the protein abundance of a light-dependent urea active transporter, DUR3-like, in its ctenidium.

PubMed

Chan, Christabel Y L; Hiong, Kum C; Boo, Mel V; Choo, Celine Y L; Wong, Wai P; Chew, Shit F; Ip, Yuen K

2018-04-19

Giant clams live in nutrient-poor reef waters of the Indo-Pacific and rely on symbiotic dinoflagellates ( Symbiodinium spp., also known as zooxanthellae) for nutrients. As the symbionts are nitrogen deficient, the host clam has to absorb exogenous nitrogen and supply it to them. This study aimed to demonstrate light-enhanced urea absorption in the fluted giant clam, Tridacna squamosa , and to clone and characterize the urea active transporter DUR3-like from its ctenidium (gill). The results indicate that T. squamosa absorbs exogenous urea, and the rate of urea uptake in the light was significantly higher than that in darkness. The DUR3-like coding sequence obtained from its ctenidium comprised 2346 bp, encoding a protein of 782 amino acids and 87.0 kDa. DUR3-like was expressed strongly in the ctenidium, outer mantle and kidney. Twelve hours of exposure to light had no significant effect on the transcript level of ctenidial DUR3-like However, between 3 and 12 h of light exposure, DUR3-like protein abundance increased progressively in the ctenidium, and became significantly greater than that in the control at 12 h. DUR3-like had an apical localization in the epithelia of the ctenidial filaments and tertiary water channels. Taken together, these results indicate that DUR3-like might participate in light-enhanced urea absorption in the ctenidium of T. squamosa When made available to the symbiotic zooxanthellae that are known to possess urease, the absorbed urea can be metabolized to NH 3 and CO 2 to support amino acid synthesis and photosynthesis, respectively, during insolation. © 2018. Published by The Company of Biologists Ltd.

The metabolic reactions in men and women during long-term head-down tilt

NASA Astrophysics Data System (ADS)

Markin, Andrey

We have demonstrated that dynamics of alterations of some biochemical blood indices during ling-term space flights and at a long duration head-down tilt (HDT) features that same directionality [Andrei Markin, Lubov Strogonova, Oleg Balashov et al, 1998]. A comparison between biochemical blood parameters at 120-day HDT was provided for groups consisting of nine men (MG1),six men (MG2) and four women (WG). All examined persons aged were exposed to "pure" HDT without resort to any prophylactic agents. Under investigations were concentrations of urea, uric acid, total cholesterol [CHO], HDL-cholesterol [HDL], triglycerides (TG), primary lipid peroxidation (LPO) products, final LPO products, tocopherol (TP) as well as activity of alanin aminotransferase (ALT), total creatin kinase (CK). For all the groups the investigated indices values were expressed as a percentage to background ones. ALT activity for the WG group had a tendency to decrease by 2-15 Women presented a moderate urea concentration lowering which ranged from 99 to 86 CHO level in WG was also elevated, and the extent to which elevated, for the most part, exceeded that of men, but beginning with the 72-nd - 84-th days of HDT an increase in MG1 become more pronounced with its retaining up to the RP. In all groups the tendency for decrease in HDL content was observed, however, it was more pronounced with men. In the RP the parameter value was increased in MG1 and MG2, but in WG it remained at the level which was observed at HDT. TG concentration women presented in the course of HDT increased, but beginning with the 49-th - 50-th day of experiment an increased in MG1 and MG2 became more pronounced. LPO products content dynamics in WG manifested as alternating increases and decreases relative to the background values (65 to 24 Comparative results of biochemical value dynamics investigation obtained in the course of a 120- day HDT demonstrated that women feature slower and less pronounced formation of metabolic response to experimental exposure as compared to men. In terms of some parameters (products of nitrogen and nucleic metabolism), men and women present dynamics of different direction, which is testimony to a woman body conservative reaction nature.

Rapamycin reduces renal hypoxia, interstitial inflammation and fibrosis in a rat model of unilateral ureteral obstruction.

PubMed

Liu, Chun-feng; Liu, Hing; Fang, Yi; Jiang, Su-hua; Zhu, Jia-ming; Ding, Xiao-qiang

2014-06-01

The purpose of this study was to explore effects of rapamycin on renal hypoxia, interstitial inflammation and fibrosis, and the expression of transforming growth factor β1 (TGF-β1), vascular endothelial growth factor (VEGF), Flk-1 and Flt-1 in a rat model of unilateral ureteral obstruction (UUO). Male Sprague-Dawley rats (n=36) were randomly divided into three groups (n=12 per group): sham surgery, UUO and UUO plus rapamycin (0.2 mg/kg/d). Serum creatinine (Scr), blood urea nitrogen, uric acid, triglycerides, cholesterol and 24-h urine protein levels were measured. The extent of interstitial fibrosis was determined by Masson's trichrome staining. ED-1 positive macrophages, type III collagen, hypoxia, TGF-1, VEGF, Flk-1, and Flt-1 mRNA and protein expressions were detected using immunohistochemical staining, real-time PCR and Western blot. UUO induced an elevation in Scr, renal hypoxia, inflammation, interstitial fibrosis, TGF-β1, VEGF, Flk-1, and Flt-1 mRNA and protein expression levels (P < 0.05). Rapamycin alleviated the UUO-induced renal hypoxia, infiltration of inflammatory cells and tubulointerstitial fibrosis (at days 3 and 7). Rapamycin also down-regulated the UUO-induced elevated expression levels of TGF-β1 and Flt-1 mRNA and protein (P < 0.05). Rapamycin decreased VEGF mRNA and protein expression at day 3, and increased Flk-1 mRNA and protein expression at day 7, compared with the UUO group (P < 0.05). Rapamycin shows beneficial effects by reducing UUO-induced renal hypoxia, inflammation and tubulointerstitial fibrosis.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lv, Mei; Liu, Zengrong; He, Bing

In previous studies, we reported molecular dynamics (MD) simulations showing that single-file water wires confined inside Y-shaped single-walled carbon nanotubes (Y-SWNTs) held strong and robust capability to convert and multiply charge signals [Y. S. Tu, P. Xiu, R. Z. Wan, J. Hu, R. H. Zhou, and H. P. Fang, Proc. Natl. Acad. Sci. U.S.A. 106, 18120 (2009); Y. Tu, H. Lu, Y. Zhang, T. Huynh, and R. Zhou, J. Chem. Phys. 138, 015104 (2013)]. It is fascinating to see whether the signal multiplication can be realized by other kinds of polar molecules with larger dipole moments (which make the experimentalmore » realization easier). In this article, we use MD simulations to study the urea-mediated signal conversion and multiplication with Y-SWNTs. We observe that when a Y-SWNT with an external charge of magnitude 1.0 e (the model of a signal at the single-electron level) is solvated in 1 M urea solutions, urea can induce drying of the Y-SWNT and fill its interiors in single-file, forming Y-shaped urea wires. The external charge can effectively control the dipole orientation of the urea wire inside the main channel (i.e., the signal can be readily converted), and this signal can further be multiplied into 2 (or more) output signals by modulating dipole orientations of urea wires in bifurcated branch channels of the Y-SWNT. This remarkable signal transduction capability arises from the strong dipole-induced ordering of urea wires under extreme confinement. We also discuss the advantage of urea as compared with water in the signal multiplication, as well as the robustness and biological implications of our findings. This study provides the possibility for multiplying signals by using urea molecules (or other polar organic molecules) with Y-shaped nanochannels and might also help understand the mechanism behind signal conduction in both physical and biological systems.« less

Geophysical monitoring and reactive transport modeling of ureolytically-driven calcium carbonate precipitation

PubMed Central

2011-01-01

Ureolytically-driven calcium carbonate precipitation is the basis for a promising in-situ remediation method for sequestration of divalent radionuclide and trace metal ions. It has also been proposed for use in geotechnical engineering for soil strengthening applications. Monitoring the occurrence, spatial distribution, and temporal evolution of calcium carbonate precipitation in the subsurface is critical for evaluating the performance of this technology and for developing the predictive models needed for engineering application. In this study, we conducted laboratory column experiments using natural sediment and groundwater to evaluate the utility of geophysical (complex resistivity and seismic) sensing methods, dynamic synchrotron x-ray computed tomography (micro-CT), and reactive transport modeling for tracking ureolytically-driven calcium carbonate precipitation processes under site relevant conditions. Reactive transport modeling with TOUGHREACT successfully simulated the changes of the major chemical components during urea hydrolysis. Even at the relatively low level of urea hydrolysis observed in the experiments, the simulations predicted an enhanced calcium carbonate precipitation rate that was 3-4 times greater than the baseline level. Reactive transport modeling results, geophysical monitoring data and micro-CT imaging correlated well with reaction processes validated by geochemical data. In particular, increases in ionic strength of the pore fluid during urea hydrolysis predicted by geochemical modeling were successfully captured by electrical conductivity measurements and confirmed by geochemical data. The low level of urea hydrolysis and calcium carbonate precipitation suggested by the model and geochemical data was corroborated by minor changes in seismic P-wave velocity measurements and micro-CT imaging; the latter provided direct evidence of sparsely distributed calcium carbonate precipitation. Ion exchange processes promoted through NH4+ production during urea hydrolysis were incorporated in the model and captured critical changes in the major metal species. The electrical phase increases were potentially due to ion exchange processes that modified charge structure at mineral/water interfaces. Our study revealed the potential of geophysical monitoring for geochemical changes during urea hydrolysis and the advantages of combining multiple approaches to understand complex biogeochemical processes in the subsurface. PMID:21943229

Diffuse Interstitial Brain Edema in Patients With End-Stage Renal Disease Undergoing Hemodialysis: A Tract-Based Spatial Statistics Study

PubMed Central

Kong, Xiang; Wen, Ji-qiu; Qi, Rong-feng; Luo, Song; Zhong, Jian-hui; Chen, Hui-juan; Ji, Gong-jun; Lu, Guang Ming; Zhang, Long Jiang

2014-01-01

Abstract To investigate white matter (WM) alterations and their correlation with cognition function in end-stage renal disease (ESRD) patients undergoing hemodialysis (HD) using diffusion tensor imaging (DTI) with tract-based spatial statistics (TBSS) approach. This prospective HIPAA-complaint study was approved by our institutional review board. Eighty HD ESRD patients and 80 sex- and age-matched healthy controls were included. Neuropsychological (NP) tests and laboratory tests, including serum creatinine and urea, were performed. DTI data were processed to obtain fractional anisotropy (FA) and mean diffusivity (MD) maps with TBSS. FA and MD difference between the 2 groups were compared. We also explored the associations of FA values in WM regions of lower FA with ages, NP tests, disease, and dialysis durations, serum creatinine and urea levels of ESRD patients. Compared with controls, HD ESRD patients had lower FA value in the corpus callosum, bilateral corona radiate, posterior thalamic radiation, left superior longitudinal fasciculus, and right cingulum (P < 0.05, FWE corrected). Almost all WM regions had increased MD in HD ESRD patients compared with controls (P < 0.05, FWE corrected). In some regions with lower FA, FA values showed moderate correlations with ages, NP tests, and serum urea levels. There was no correlation between FA values and HD durations, disease durations, and serum creatinine levels of ESRD patients (all P > 0.05). Diffuse interstitial brain edema and moderate WM integrity disruption occurring in HD ESRD patients, which correlated with cognitive dysfunction, and serum urea levels might be a risk factor for these WM changes. PMID:25526483

Predicting duration of mechanical ventilation in patients with carbon monoxide poisoning: a retrospective study.

PubMed

Shen, Chih-Hao; Peng, Chung-Kan; Chou, Yu-Ching; Pan, Ke-Ting; Chang, Shun-Cheng; Chang, Shan-Yueh; Huang, Kun-Lun

2015-02-01

Patients with severe carbon monoxide (CO) poisoning may develop acute respiratory failure, which needs endotracheal intubation and mechanical ventilation (MV). The objective of this study was to identify the predictors for duration of MV in patients with severe CO poisoning and acute respiratory failure. This is a retrospective observational study of 796 consecutive patients diagnosed with acute CO poisoning that presented to the emergency department. Patients who received MV were divided into 2 groups: the early extubation (EE) consisting of patients who were on MV for less than 72 hours and the nonearly extubation (NEE) consisting of patients who were on MV for more than 72 hours. Demographic and clinical data of the two groups were extracted for analysis. The intubation rate of all CO-poisoned patients was 23.4%. A total of 168 patients were enrolled in this study. The main source of CO exposure was intentional CO poisoning by charcoal burning (137 patients). Positive toxicology screening result was found in 104 patients (61.9%). The EE group had 105 patients (62.5%). On arriving at the emergency department, high incidence of hypotension; high white blood cell count; and elevation of blood urea nitrogen, creatinine, aspartate aminotransferase, alanine aminotransferase, creatine kinase, and troponin-I levels were statistically significant in the NEE group (P < .05). Positive toxicology screening result was statistically significant in the EE group (P < .05). In a multivariate analysis, elevation of troponin-I level was an independent factor for NEE (odds ratio, 1.305; 95% confidence interval, 1.024-1.663; P = .032). Positive toxicology screening result was an independent factor for EE (odds ratio, 0.222; 95% confidence interval, 0.101-0.489; P = .001). A positive toxin screen predicts extubation within the first 72 hours for patients with severe CO poisoning and acute respiratory failure. On the other hand, elevation of initial troponin-I level is a predictor for a longer duration of MV. Copyright © 2014 Elsevier Inc. All rights reserved.

Immediate metabolic effects of different nutritional regimens in critically ill medical patients.

PubMed

Müller, T F; Müller, A; Bachem, M G; Lange, H

1995-07-01

Metabolic effects of different caloric regimens were investigated in nonsurgical, medical patients with multiple-organ failure (MOF). Seven total parenteral nutrition (TPN) regimens were administered, differing in amount (14, 28, and 56 kcal/kg per day, i.e., hypo-, iso-, and hypercaloric nutrition, respectively) and distribution [carbohydrates (COH), amino acids (AA), long-chain and medium-chain triglycerides (LCT/MCT)] of calories. Each regimen was administered over 12 h. Metabolism was monitored by energy expenditure (EE), body temperature (BT), protein breakdown (PB), and blood glucose and serum lactate levels. Measurements were started within 2 days of MOF onset. The study was conducted in a medical intensive care unit. Twenty patients with MOF on mechanical ventilation (mean Apache II score x = 26) were investigated. The mean values of the EE (x = 31 kcal/kg per day), BT (x = 38 degrees C), PB (x = 1.5 g/kg per day), and lactate (x = 2.0 mmol/l) and glucose level (x = 222 mg/dl) parameters were elevated. EE, BT, and lactate and glucose levels were significantly lower under hypocaloric nutrition than during iso- and hypercaloric nutrition (p < 0.01). Differences in the metabolic effects of LCT and MCT were not significant. PB was significantly elevated under hypercaloric nutrition (p < 0.01). Protein balance was positive under hypercaloric nutrition, and negative under iso- and hypocaloric nutrition. In nonsurgical, medical patients neither hypercaloric nor isocaloric nutritional support prevented protein catabolism; in contrast, they enhanced the metabolic burden measured by EE, thermogenesis, urea production rate, and glucose and lactate levels. A hypocaloric regimen is therefore recommended for these patients during the early phase of MOF.

Effects of partial ruminal defaunation on urea-nitrogen recycling, nitrogen metabolism, and microbial nitrogen supply in growing lambs fed low or high dietary crude protein concentrations.

PubMed

Kiran, D; Mutsvangwa, T

2010-03-01

Urea-nitrogen recycling to the gastrointestinal tract (GIT), N metabolism, and urea transporter-B (UT-B) mRNA abundance in ruminal epithelium were evaluated in partially defaunated (PDFAUN) and faunated (FAUN) growing lambs fed 2 levels (10%, low, or 15%, high) of dietary CP (DM basis). Four Suffolk ram lambs (43.9 +/- 1.4 kg initial BW) were used in a 4 x 4 Latin square design with 27-d periods. Sunflower oil was fed (6%; DM basis) as an anti-protozoal agent. Nitrogen balance was measured from d 22 to 26, with concurrent measurement of urea-N kinetics using continuous intrajugular infusions of [(15)N(15)N]-urea. Feeding sunflower oil decreased (P < 0.01) total ruminal protozoa by 88%, and this was associated with a decrease (P < 0.01) in ruminal ammonia-N concentrations. Endogenous production of urea-N (UER; 26.1 vs. 34.6 g/d) and urea-N loss in urine (UUE; 10.1 vs. 15.7 g/d) were less (P < 0.01), and urea-N entering the GIT (GER; 16.0 vs. 18.9 g/d) tended to be less (P = 0.06) in PDFAUN as compared with FAUN lambs. However, as a proportion of UER, GER was greater (P < 0.01) and the proportion of recycled urea-N that was utilized for anabolism (i.e., UUA) tended to be greater (P = 0.09) in PDFAUN lambs. Partial defaunation increased (P < 0.01) microbial N supply. The UER, GER, and UUE were greater (P < 0.01) in lambs fed the high diet. However, as a proportion of UER, GER and its anabolic use were greater (P < 0.01) in lambs fed the low diet. The expression of UT-B mRNA in PDFAUN lambs was numerically greater (by 20%; P = 0.15) compared with FAUN lambs. In summary, results indicate that part of the mechanism for improved N utilization in defaunated ruminants is an increase in the proportion of endogenous urea-N output that is recycled to the GIT, thus potentially providing additional N for microbial growth.

Metabolic profile of serum and follicular fluid from postpartum dairy cows during summer and winter.

PubMed

Alves, Benner G; Alves, Kele A; Martins, Muller C; Braga, Lucas S; Silva, Thiago H; Alves, Bruna G; Santos, Ricarda M; Silva, Thiago V; Viu, Marco A O; Beletti, Marcello E; Jacomini, José O; Gambarini, Maria L

2014-01-01

This study was designed to monitor the biochemical profiles of serum and follicular fluid (FF) of postpartum dairy cows during the summer (n=30) and winter (n=30). Blood and FF (follicles ≥ 9 mm) were obtained from Girolando cows at 30, 45, 60, 75 and 90 days postpartum. The samples were collected and analysed to determine glucose, total cholesterol (TC), triglyceride (TG), urea, sodium (Na), potassium (K) and calcium (Ca) levels. Throughout the study, the following clinical variables were measured: rectal temperature (RT), respiratory rate (RR) and body condition score (BCS). In addition, the temperature humidity index (THI) was calculated for each season. During the summer season, THI was higher, BCS decreased, there was an increase in RT, and glucose, urea, Na and K serum levels were decreased (P<0.05). The levels of TC, TG, urea, K and Ca in follicular fluid increased (P<0.05). Positive correlations (P<0.05) were observed between the serum and FF levels for glucose (r=0.29), TC (r=0.24) and Ca (r=0.30). Therefore, the biochemical profile of serum and FF of dairy cows under summer heat-stress conditions demonstrates marked changes that may impair fertility during lactation.

Effect of strawberry (Fragaria × ananassa) leaf extract on diabetic nephropathy in rats

PubMed Central

Ibrahim, Doaa S; Abd El-Maksoud, Marwa A E

2015-01-01

Diabetic nephropathy is a clinical syndrome characterized by albuminuria, hypertension and progressive renal insufficiency. The aim of this study was to investigate the effect of strawberry (Fragaria × ananassa) leaf extract on diabetic nephropathy in rats. Streptozotocin (STZ) diabetic rats were orally treated with three doses (50, 100 and 200 mg/kg) of strawberry leaf extract for 30 days. Nephropathy biomarkers in plasma and kidney were examined at the end of the experiment. The three doses of strawberry leaf extract significantly decreased the levels of blood glucose, urea nitrogen, plasma creatinine, kidney injury molecule (Kim)-1, renal malondialdehyde (MDA), tumour necrosis factor alpha (TNF-α), interleukin (IL)- 6 and caspase-3 in diabetic rats. Meanwhile, the levels of plasma insulin, albumin, uric acid, renal catalase (CAT), superoxide dismutase (SOD) and vascular endothelial growth factor A (VEGF-A) were significantly elevated in diabetic rats treated with strawberry leaf extract. These results indicate the role of strawberry leaves extract as anti-diabetic, antioxidant, anti-inflammatory and anti-apoptosis in diabetic nephropathy. PMID:25645466

Experimental drug-induced changes in renal function and biodistribution of /sup 99m/Tc-MDP

DOE Office of Scientific and Technical Information (OSTI.GOV)

McAfee, J.G.; Singh, A.; Roskopf, M.

Increased renal uptake of /sup 99m/Tc methylene diphosphonate (MDP) was observed irregularly in rats after methotrexate, vincristine or gentamicin, administered separately. Cisplatin regularly induced a dose-related increased MDP uptake which correlated with the degree of tubular damage histologically. The augmented MDP renal uptake was not consistently accompanied by a decreased clearance of simultaneously injected I-131 Hippuran, particularly at lower drug dose levels. This observation agreed with previous evidence that the mechanisms of tubular transport of diphosphonates and organic acids like Hippuran are different. At higher dose levels, the augmented MDP uptake was accompanied by increased renal calcium, hypophosphatemia, elevated serummore » urea nitrogen and creatinine, and only occasional, mild hypercalcemia. The magnitude of the increased renal uptake of MDP observed could not be explained by alterations in iron metabolism or by dehydration. Drug-induced renal retention of MDP by a factor of 2 or more above normal appears to be a useful indicator of tubular damage when other parameters of renal function are sometimes normal.« less

Salicylic Acid Attenuates Gentamicin-Induced Nephrotoxicity in Rats

PubMed Central

Randjelovic, Pavle; Veljkovic, Slavimir; Stojiljkovic, Nenad; Jankovic-Velickovic, Ljubinka; Sokolovic, Dusan; Stoiljkovic, Milan; Ilic, Ivan

2012-01-01

Gentamicin (GM) is a widely used antibiotic against serious and life-threatening infections, but its usefulness is limited by the development of nephrotoxicity. The present study was designed to determine the protective effect of salicylic acid (SA) in gentamicin-induced nephrotoxicity in rats. Quantitative evaluation of gentamicin-induced structural alterations and degree of functional alterations in the kidneys were performed by histopathological and biochemical analyses in order to determine potential beneficial effects of SA coadministration with gentamicin. Gentamicin was observed to cause a severe nephrotoxicity which was evidenced by an elevation of serum urea and creatinine levels. The significant increases in malondialdehyde (MDA) levels and protein carbonyl groups indicated that GM-induced tissue injury was mediated through oxidative reactions. On the other hand, simultaneous SA administration protected kidney tissue against the oxidative damage and the nephrotoxic effect caused by GM treatment. Exposure to GM caused necrosis of tubular epithelial cells. Necrosis of tubules was found to be prevented by SA pretreatment. The results from our study indicate that SA supplement attenuates oxidative-stress associated renal injury by reducing oxygen free radicals and lipid peroxidation in gentamicin-treated rats. PMID:22666115

Ammonia as a respiratory gas in water and air-breathing fishes.

PubMed

Randall, David J; Ip, Yuen K

2006-11-01

Ammonia is produced in the liver and excreted as NH(3) by diffusion across the gills. Elevated ammonia results in an increase in gill ventilation, perhaps via stimulation of gill oxygen chemo-receptors. Acidification of the water around the fish by carbon dioxide and acid excretion enhances ammonia excretion and constitutes "environmental ammonia detoxification". Fish have difficulties in excreting ammonia in alkaline water or high concentrations of environmental ammonia, or when out of water. The mudskipper, Periphthalmodon schlosseri, is capable of active NH(4)(+) transport, maintaining low internal levels of ammonia. To prevent a back flux of NH(3), these air-breathing fish can increase gill acid excretion and reduce the membrane NH(3) permeability by modifying the phospholipid and cholesterol compositions of their skin. Several air-breathing fish species can excrete ammonia into air through NH(3) volatilization. Some fish detoxify ammonia to glutamine or urea. The brains of some fish can tolerate much higher levels of ammonia than other animals. Studies of these fish may offer insights into the nature of ammonia toxicity in general.

The role of nickel in urea assimilation by algae.

PubMed

Rees, T A; Bekheet, I A

1982-12-01

Nickel is required for urease synthesis by Phaeodactylum tricornutum and Tetraselmis subcordiformis and for growth on urea by Phaeodactylum. There is no requirement for nickel for urea amidolyase synthesis by Chlorella fusca var. vacuolata. Neither copper nor palladium can substitute for nickel but cobalt partially restored urease activity in Phaeodactylum. The addition of nickel to nickel-deficient cultures of Phaeodactylum or Tetraselmis resulted in a rapid increase of urease activity to 7-30 times the normal level; this increase was not inhibited by cycloheximide. It is concluded that nickel-deficient cells over-produce a non-functional urease protein and that either nickel or the functional urease enzyme participates in the regulation of the production of urease protein.

Total antioxidant and oxidant status of plasma and renal tissue of cisplatin-induced nephrotoxic rats: protection by floral extracts of Calendula officinalis Linn.

PubMed

Verma, Pawan Kumar; Raina, Rajinder; Sultana, Mudasir; Singh, Maninder; Kumar, Pawan

2016-01-01

The present study was aimed to determine the total antioxidant status (TAS), total oxidant status (TOS) and oxidative stress index (OSI) of plasma and renal tissue in cisplatin (cDDP) induced nephrotoxic rats and its protection by treatments with floral extracts of Calendula officinalis Linn. Treatment with cDDP elevated (p < 0.05) the levels of blood urea nitrogen, creatinine (CR), TOS, OSI and malondialdehyde (MDA) but lowered (p < 0.05) total plasma proteins, TAS, total thiols (TTH), blood glutathione (GSH) and antioxidant enzymes compared to the control group. Pre- and post-treatments of ethanolic floral extract of C. officinalis along with cDDP restored (p > 0.05) CR, albumin, TOS, GSH and activities of antioxidant enzymes in blood and renal tissue. Ethanolic extract treatments reduced (p < 0.05) MDA level in renal tissue without restoring the erythrocyte MDA level following cDDP treatment. These observations were further supported by the histopathological findings in renal tissue. Observations of the present study have shown that treatments with ethanolic floral extract of C. officinalis protect cDDP induced nephrotoxicity by restoring antioxidant system of the renal tissue.

Diversity of nitrogen isotopes and protein status in caribou: implications for monitoring northern ungulates

USGS Publications Warehouse

Gustine, David D.; Barboza, Perry S.; Lawler, James P.; Adams, Layne G.; Parker, Kathy L.; Arthur, Steve M.; Shults, Brad S.

2012-01-01

Nutritional condition is an important determinant of productivity and survival in caribou (Rangifer tarandus). We used samples of excreta (n  =  1,150) to estimate diet composition from microhistology and 2 isotopic proxies of protein status for 2 ecotypes of caribou in 4 herds in late winter (2006–2008). Isotopes of nitrogen (δ15N in parts per thousand [‰]) from excreta samples (urea, diet, and body N) were used to estimate indexes of protein status: the proportion of urea N derived from body N (p-UN) and the difference between the δ15N of the body and urinary urea (Δbody-urea). We examined dietary and terrain characteristics, δ15N, p-UN, and Δbody-urea by ecotype, herd, year, and foraging site. Multiple regression and an information-theoretic approach were used to evaluate correlates of protein status at each foraging site. The dietary and terrain characteristics of foraging sites did not vary by ecotype or herd (P > 0.108); diets were dominated by lichens (68% ± 14.1% SD). The δ15N of urea, diet, body N, p-UN, and Δbody-urea varied among foraging sites within each herd (P 15N of urinary urea was typically low (−4.68‰ ± 2.67‰ SD). Dietary N also had low δ15N (−4.18‰ ± 0.92‰ SD), whereas body N was generally heavier in 15N (2.20‰ ± 1.56‰ SD) than urinary urea or the diet. Both measures of protein status were similarly diverse between ecotypes and among herds, which limited their applicability to monitor protein status at the population level. Although we observed limitations to interpreting estimates of p-UN from highly vagile ungulates, the Δbody-urea may prove to be a useful index of protein status at smaller spatial and temporal scales. Indeed, a portion of the observed variance (r2  =  0.26) in Δbody-urea at each foraging site was explained by the proportion of shrubs in the winter diet. There remains potential in using δ15N in excreta as a noninvasive tool for evaluating protein status in northern ungulates; however, considerable analytical and sampling challenges remain for applying these isotopic approaches at large scales.

Arginase 2 Suppresses Renal Carcinoma Progression via Biosynthetic Cofactor Pyridoxal Phosphate Depletion and Increased Polyamine Toxicity.

PubMed

Ochocki, Joshua D; Khare, Sanika; Hess, Markus; Ackerman, Daniel; Qiu, Bo; Daisak, Jennie I; Worth, Andrew J; Lin, Nan; Lee, Pearl; Xie, Hong; Li, Bo; Wubbenhorst, Bradley; Maguire, Tobi G; Nathanson, Katherine L; Alwine, James C; Blair, Ian A; Nissim, Itzhak; Keith, Brian; Simon, M Celeste

2018-05-04

Kidney cancer, one of the ten most prevalent malignancies in the world, has exhibited increased incidence over the last decade. The most common subtype is "clear cell" renal cell carcinoma (ccRCC), which features consistent metabolic abnormalities, such as highly elevated glycogen and lipid deposition. By integrating metabolomics, genomic, and transcriptomic data, we determined that enzymes in multiple metabolic pathways are universally depleted in human ccRCC tumors, which are otherwise genetically heterogeneous. Notably, the expression of key urea cycle enzymes, including arginase 2 (ARG2) and argininosuccinate synthase 1 (ASS1), is strongly repressed in ccRCC. Reduced ARG2 activity promotes ccRCC tumor growth through at least two distinct mechanisms: conserving the critical biosynthetic cofactor pyridoxal phosphate and avoiding toxic polyamine accumulation. Pharmacological approaches to restore urea cycle enzyme expression would greatly expand treatment strategies for ccRCC patients, where current therapies only benefit a subset of those afflicted with renal cancer. Copyright © 2018 Elsevier Inc. All rights reserved.

One-step synthesis of layered yttrium hydroxides in immiscible liquid-liquid systems: Intercalation of sterically-bulky hydrophobic organic anions and doping of europium ions

NASA Astrophysics Data System (ADS)

Watanabe, Mebae; Fujihara, Shinobu

2014-02-01

Inorganic-organic layered rare-earth compounds were synthesized on the basis of a biphasic liquid-liquid system in one pot. Layered yttrium hydroxides (LYHs) were chosen as a host material for the intercalation of hydrophobic organic guest anions such as benzoate, sebacate, or laurate. In a typical synthesis, an organic phase dissolving carboxylic acid was placed in contact with an equal amount of an aqueous phase dissolving yttrium nitrate n-hydrate and urea. At elevated temperatures up to 80 °C, urea was hydrolyzed to release hydroxyl anions which were used to form yttrium hydroxide layers. LYHs were then precipitated with the intercalation of carboxylate anions delivered from the organic phase under the distribution law. The structure and the morphology of the LYHs could be modulated by the intercalated anions. Doped with Eu3+ ions, the LYHs exhibited red photoluminescence which was enhanced by the intercalated anions due to the antenna effect.

Nigella sativa oil attenuates chronic nephrotoxicity induced by oral sodium nitrite: Effects on tissue fibrosis and apoptosis.

PubMed

Al-Gayyar, Mohammed M H; Hassan, Hanan M; Alyoussef, Abdullah; Abbas, Ahmed; Darweish, Mohamed M; El-Hawwary, Amany A

2016-03-01

Sodium nitrite, a food preservative, has been reported to increase oxidative stress indicators such as lipid peroxidation, which can affect different organs including the kidney. Here, we investigated the toxic effects of oral sodium nitrite on kidney function in rats and evaluated potential protective effects of Nigella sativa oil (NSO). Seventy adult male Sprague-Dawley rats received 80 mg/kg sodium nitrite orally in the presence or absence of NSO (2.5, 5, and 10 ml/kg) for 12 weeks. Morphological changes were assessed by hematoxylin and eosin, Mallory trichome, and periodic acid-Schiff staining. Renal tissues were used for measurements of oxidative stress markers, C-reactive protein, cytochrome C oxidase, transforming growth factor (TGF)-beta1, monocyte chemotactic protein (MCP)-1, pJNK/JNK, and caspase-3. NSO significantly reduced sodium nitrite-induced elevation in serum urea and creatinine, as well as increasing normal appearance of renal tissue. NSO also prevented reductions in glycogen levels caused by sodium nitrite alone. Moreover, NSO treatment resulted in dose-dependent significant reductions in fibrosis markers after sodium nitrite-induced 3- and 2.7-fold increase in MCP-1 and TGF-beta1, respectively. Finally, NSO partially reduced the elevated caspase-3 and pJNK/JNK. NSO ameliorates sodium nitrite-induced nephrotoxicity through blocking oxidative stress, attenuation of fibrosis/inflammation, restoration of glycogen level, amelioration of cytochrome C oxidase, and inhibition of apoptosis.

Metabolic profiles of exercise in patients with McArdle disease or mitochondrial myopathy

PubMed Central

Sharma, Rohit; Tadvalkar, Laura; Clish, Clary B.; Haller, Ronald G.; Mootha, Vamsi K.

2017-01-01

McArdle disease and mitochondrial myopathy impair muscle oxidative phosphorylation (OXPHOS) by distinct mechanisms: the former by restricting oxidative substrate availability caused by blocked glycogen breakdown, the latter because of intrinsic respiratory chain defects. We applied metabolic profiling to systematically interrogate these disorders at rest, when muscle symptoms are typically minimal, and with exercise, when symptoms of premature fatigue and potential muscle injury are unmasked. At rest, patients with mitochondrial disease exhibit elevated lactate and reduced uridine; in McArdle disease purine nucleotide metabolites, including xanthine, hypoxanthine, and inosine are elevated. During exercise, glycolytic intermediates, TCA cycle intermediates, and pantothenate expand dramatically in both mitochondrial disease and control subjects. In contrast, in McArdle disease, these metabolites remain unchanged from rest; but urea cycle intermediates are increased, likely attributable to increased ammonia production as a result of exaggerated purine degradation. Our results establish skeletal muscle glycogen as the source of TCA cycle expansion that normally accompanies exercise and imply that impaired TCA cycle flux is a central mechanism of restricted oxidative capacity in this disorder. Finally, we report that resting levels of long-chain triacylglycerols in mitochondrial myopathy correlate with the severity of OXPHOS dysfunction, as indicated by the level of impaired O2 extraction from arterial blood during peak exercise. Our integrated analysis of exercise and metabolism provides unique insights into the biochemical basis of these muscle oxidative defects, with potential implications for their clinical management. PMID:28716914

Establishing standards for studying renal function in mice through measurements of body size-adjusted creatinine and urea levels.

PubMed

Rodrigues, Wellington Francisco; Miguel, Camila Botelho; Napimoga, Marcelo Henrique; Oliveira, Carlo Jose Freire; Lazo-Chica, Javier Emilio

2014-01-01

Strategies for obtaining reliable results are increasingly implemented in order to reduce errors in the analysis of human and veterinary samples; however, further data are required for murine samples. Here, we determined an average factor from the murine body surface area for the calculation of biochemical renal parameters, assessed the effects of storage and freeze-thawing of C57BL/6 mouse samples on plasmatic and urinary urea, and evaluated the effects of using two different urea-measurement techniques. After obtaining 24 h urine samples, blood was collected, and body weight and length were established. The samples were evaluated after collection or stored at -20°C and -70°C. At different time points (0, 4, and 90 days), these samples were thawed, the creatinine and/or urea concentrations were analyzed, and samples were restored at these temperatures for further measurements. We show that creatinine clearance measurements should be adjusted according to the body surface area, which was calculated based on the weight and length of the animal. Repeated freeze-thawing cycles negatively affected the urea concentration; the urea concentration was more reproducible when using the modified Berthelot reaction rather than the ultraviolet method. Our findings will facilitate standardization and optimization of methodology as well as understanding of renal and other biochemical data obtained from mice.

Time course of the acute response of the North Pacific spiny dogfish shark (Squalus suckleyi) to low salinity.

PubMed

Guffey, Samuel C; Goss, Greg G

2014-05-01

Dogfish are considered stenohaline sharks but are known to briefly enter estuaries. The acute response of North Pacific spiny dogfish (Squalus suckleyi) to lowered salinity was tested by exposing sharks to 21‰ salinity for 48 h. Temporal trends in blood pH, plasma osmolality, CO2, HCO3(-), Na(+), Cl(-), K(+), and urea concentrations, and in the rates of urea efflux and O2 consumption, were quantified. The rate of O2 consumption exhibited cyclic variation and was significantly depressed by lowered salinity. After 9 h, plasma [Cl(-)] stabilized at 9% below initial levels, while plasma [Na(+)] decreased by more than 20% within the first 12 h. Plasma [urea] dropped by 15% between 4 and 6 h, and continued to decrease. The rate of urea efflux increased over time, peaking after 36 h at 72% above the initial rate. Free-swimming sharks subjected to the same salinity challenge survived over 96 h and differed from cannulated sharks with respect to patterns of Na(+) and urea homeostasis. This high-resolution study reveals that dogfish exposed to 21‰ salinity can maintain homeostasis of Cl(-) and pH, but Na(+) and urea continue to be lost, likely accounting for the inability of the dogfish to fully acclimate to reduced salinity. Copyright © 2014 Elsevier Inc. All rights reserved.

Reduced bioavailable manganese causes striatal urea cycle pathology in Huntington's disease mouse model.

PubMed

Bichell, Terry Jo V; Wegrzynowicz, Michal; Tipps, K Grace; Bradley, Emma M; Uhouse, Michael A; Bryan, Miles; Horning, Kyle; Fisher, Nicole; Dudek, Karrie; Halbesma, Timothy; Umashanker, Preethi; Stubbs, Andrew D; Holt, Hunter K; Kwakye, Gunnar F; Tidball, Andrew M; Colbran, Roger J; Aschner, Michael; Neely, M Diana; Di Pardo, Alba; Maglione, Vittorio; Osmand, Alexander; Bowman, Aaron B

2017-06-01

Huntington's disease (HD) is caused by a mutation in the huntingtin gene (HTT), resulting in profound striatal neurodegeneration through an unknown mechanism. Perturbations in the urea cycle have been reported in HD models and in HD patient blood and brain. In neurons, arginase is a central urea cycle enzyme, and the metal manganese (Mn) is an essential cofactor. Deficient biological responses to Mn, and reduced Mn accumulation have been observed in HD striatal mouse and cell models. Here we report in vivo and ex vivo evidence of a urea cycle metabolic phenotype in a prodromal HD mouse model. Further, either in vivo or in vitro Mn supplementation reverses the urea-cycle pathology by restoring arginase activity. We show that Arginase 2 (ARG2) is the arginase enzyme present in these mouse brain models, with ARG2 protein levels directly increased by Mn exposure. ARG2 protein is not reduced in the prodromal stage, though enzyme activity is reduced, indicating that altered Mn bioavailability as a cofactor leads to the deficient enzymatic activity. These data support a hypothesis that mutant HTT leads to a selective deficiency of neuronal Mn at an early disease stage, contributing to HD striatal urea-cycle pathophysiology through an effect on arginase activity. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

Vascular toxicity of urea, a new "old player" in the pathogenesis of chronic renal failure induced cardiovascular diseases.

PubMed

Giardino, Ida; D'Apolito, Maria; Brownlee, Michael; Maffione, Angela Bruna; Colia, Anna Laura; Sacco, Michele; Ferrara, Pietro; Pettoello-Mantovani, Massimo

2017-12-01

Chronic kidney disease in children is an irreversible process that may lead to end-stage renal disease. The mortality rate in children with end-stage renal disease who receive dialysis increased dramatically in the last decade, and it is significantly higher compared with the general pediatric population. Furthermore, dialysis and transplant patients, who have developed end-stage renal disease during childhood, live respectively far less as compared with age/race-matched populations. Different reports show that cardiovascular disease is the leading cause of death in children with end-stage renal disease and in adults with childhood-onset chronic kidney disease, and that children with chronic kidney disease are in the highest risk group for the development of cardiovascular disease. Urea, which is generated in the liver during catabolism of amino acids and other nitrogenous metabolites, is normally excreted into the urine by the kidneys as rapidly as it is produced. When renal function is impaired, increasing concentrations of blood urea will steadily accumulate. For a long time, urea has been considered to have negligible toxicity. However, the finding that plasma urea is the only significant predictor of aortic plaque area fraction in an animal model of chronic renal failure -accelerated atherosclerosis, suggests that the high levels of urea found in chronic dialysis patients might play an important role in accelerated atherosclerosis in this group of patients. The aim of this review was to provide novel insights into the role played by urea in the pathogenesis of accelerated cardiovascular disease in renal failure.

Vascular toxicity of urea, a new “old player” in the pathogenesis of chronic renal failure induced cardiovascular diseases

PubMed Central

D’Apolito, Maria; Brownlee, Michael; Maffione, Angela Bruna; Colia, Anna Laura; Sacco, Michele; Ferrara, Pietro; Pettoello-Mantovani, Massimo

2017-01-01

Chronic kidney disease in children is an irreversible process that may lead to end-stage renal disease. The mortality rate in children with end-stage renal disease who receive dialysis increased dramatically in the last decade, and it is significantly higher compared with the general pediatric population. Furthermore, dialysis and transplant patients, who have developed end-stage renal disease during childhood, live respectively far less as compared with age/race-matched populations. Different reports show that cardiovascular disease is the leading cause of death in children with end-stage renal disease and in adults with childhood-onset chronic kidney disease, and that children with chronic kidney disease are in the highest risk group for the development of cardiovascular disease. Urea, which is generated in the liver during catabolism of amino acids and other nitrogenous metabolites, is normally excreted into the urine by the kidneys as rapidly as it is produced. When renal function is impaired, increasing concentrations of blood urea will steadily accumulate. For a long time, urea has been considered to have negligible toxicity. However, the finding that plasma urea is the only significant predictor of aortic plaque area fraction in an animal model of chronic renal failure -accelerated atherosclerosis, suggests that the high levels of urea found in chronic dialysis patients might play an important role in accelerated atherosclerosis in this group of patients. The aim of this review was to provide novel insights into the role played by urea in the pathogenesis of accelerated cardiovascular disease in renal failure. PMID:29483797

The association between a low urine pH and the components of metabolic syndrome in the Korean population: Findings based on the 2010 Korea National health and nutrition examination survey

PubMed Central

Cho, Young Hye; Lee, Sang Yeoup; Jeong, Dong Wook; Choi, Eun Jung; Nam, Kyung Jee; Kim, Yun Jin; Lee, Jeong Gyu; Yi, Yu Hyone; Tak, Young Jin; Cho, Byung Mann; Lee, Soo Bong; Lee, Ka Young

2014-01-01

Background: Low urine pH is related to obesity and insulin resistance, which are components of metabolic syndrome (MS). The aim of this study was to identify the relation between a low urine pH and MS after controlled for other covariates including demographic and lifestyle factors in adult Korean population. Materials and Methods: We analyzed data from the 2010 Korea National Health and Nutrition Examination Survey, a cross-sectional and nationally representative survey and 1960 men and 2702 women were included in this study. Study subjects were divided into the group with urine pH <5.5 and the group with urine pH ≥5.5 refer to literature. We then evaluated the association between low urine pH and MS. Results: After adjusting for age, sex, smoking status, drinking status, regular exercise, and blood urea nitrogen level, the odds ratio (OR) for the presence of MS in the group with urine pH <5.5 was 1.350 (95% confidence interval [95% CI]: 1.158-1.573) using the American Heart Association/National Heart, Lung, and Blood Institute criteria or 1.304 (95% CI: 1.082-1.572) using the International Diabetes Federation criteria. Among MS components, elevated fasting glucose (OR: 1.231, 95% CI: 1.058-1.433, P = 0.007) and elevated triglyceride (TG) (OR: 1.389, 95% CI: 1.189-1.623, P < 0.001) showed a significantly high OR. Conclusion: The findings confirmed that low urine pH is associated with MS in the Korean population. Among MS components, elevated fasting glucose and elevated TG showed a significantly high OR. PMID:25364357

Non-lipid effects of rosuvastatin-fenofibrate combination therapy in high-risk Asian patients with mixed hyperlipidemia.

PubMed

Lee, Sang-Hak; Cho, Kyoung-Im; Kim, Jang-Young; Ahn, Young Keun; Rha, Seung-Woon; Kim, Yong-Jin; Choi, Yun-Seok; Choi, Si Wan; Jeon, Dong Woon; Min, Pil-Ki; Choi, Dong-Ju; Baek, Sang Hong; Kim, Kwon Sam; Byun, Young Sup; Jang, Yangsoo

2012-03-01

The aim of this study is to compare the non-lipid effects of rosuvastatin-fenofibrate combination therapy with rosuvastatin monotherapy in high-risk Asian patients with mixed hyperlipidemia. A total of 236 patients were initially screened. After six weeks of diet and life style changes, 180 of these patients were randomly assigned to receive one of two regimens: rosuvastatin 10 mg plus fenofibrate 160 mg or rosuvastatin 10 mg. The primary outcome variables were the incidences of muscle or liver enzyme elevation. The patients were followed for 24 weeks during drug treatment and for an additional four weeks after drug discontinuation. The rates of the primary outcome variables were similar between the two groups (2.8% and 3.9% in the combination and the rosuvastatin groups, respectively, p=1.00). The combination group had more, but not significantly, common treatment-related adverse events (AEs) (13.3% and 5.6%, respectively) and drug discontinuation due to AEs (10.0% and 3.3%, respectively) than the rosouvastatin group. Combination therapy was associated with higher elevations in homocysteine, blood urea nitrogen, and serum creatinine, whereas elevation in alanine aminotransferase was greater in the rosuvastatin group. Leukocyte count and hemoglobin level decreased to a greater extent in the combination group. The combination group showed greater reductions in TG and elevation in HDL-cholesterol. In our study population, the rosuvastatin-fenofibrate combination resulted in comparable incidences of myo- or hepatotoxicity as rosuvastatin monotherapy. However, this combination may need to be used with caution in individuals with underlying pathologies such as renal dysfunction (NCT01414803). Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Reduction Expansion Synthesis as Strategy to Control Nitrogen Doping Level and Surface Area in Graphene

PubMed Central

Canty, Russell; Gonzalez, Edwin; MacDonald, Caleb; Osswald, Sebastian; Zea, Hugo; Luhrs, Claudia C.

2015-01-01

Graphene sheets doped with nitrogen were produced by the reduction-expansion (RES) method utilizing graphite oxide (GO) and urea as precursor materials. The simultaneous graphene generation and nitrogen insertion reactions are based on the fact that urea decomposes upon heating to release reducing gases. The volatile byproducts perform two primary functions: (i) promoting the reduction of the GO and (ii) providing the nitrogen to be inserted in situ as the graphene structure is created. Samples with diverse urea/GO mass ratios were treated at 800 °C in inert atmosphere to generate graphene with diverse microstructural characteristics and levels of nitrogen doping. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were used to study the microstructural features of the products. The effects of doping on the samples structure and surface area were studied by X-ray diffraction (XRD), Raman Spectroscopy, and Brunauer Emmet Teller (BET). The GO and urea decomposition-reduction process as well as nitrogen-doped graphene stability were studied by thermogravimetric analysis (TGA) coupled with mass spectroscopy (MS) analysis of the evolved gases. Results show that the proposed method offers a high level of control over the amount of nitrogen inserted in the graphene and may be used alternatively to control its surface area. To demonstrate the practical relevance of these findings, as-produced samples were used as electrodes in supercapacitor and battery devices and compared with conventional, thermally exfoliated graphene. PMID:28793618

Acute toxicity assessment of choline by inhalation, intraperitoneal and oral routes in Balb/c mice.

PubMed

Mehta, Amit Kumar; Arora, Naveen; Gaur, Shailendra Nath; Singh, Bhanu Pratap

2009-08-01

Studies suggest that choline has potential to be used as a dietary supplement and a drug for immune inflammatory diseases like asthma and rhinitis. But there are apprehensions regarding adverse effects of choline when given orally in high doses. To address this knowledge gap, toxicity assessment of choline chloride was carried out by intranasal (i.n.), oral and intraperitoneal (i.p.) routes in Balb/c mice for 28days. Body weight, food and water consumption of mice were recorded daily. Hematology and clinical chemistry were assessed to check hepatocellular functions and morphological alterations of the cells. Splenocyte counts were analysed for evaluating cellular immunity. Liver function test was performed by assaying different enzyme systems in serum such as, urea, blood urea nitrogen (BUN), creatinine, alanine aminotransferase (ALT), and aspartate aminotransferase (AST). Body weight, food and water consumption did not differ between mice treated with choline and the saline control group. Hematologic and biochemical variables were not affected with any increase in serum toxicity marker enzymes indicating normal liver functioning. Choline administration did not affect total cholesterol and high density lipoprotein levels as compared to their respective controls. Urea and blood urea nitrogen levels in choline treated mice were not different than controls. Creatinine level was, however, higher than control in i.p. treatment group, but other parameters were normal. In conclusion, the repeated consumption of choline chloride via i.n. and oral or i.p. routes did not cause toxicity in mice in the toxicological endpoints examined.

Characteristics of NO cycle coupling with urea cycle in non-hyperammonemic carriers of ornithine transcarbamylase deficiency.

PubMed

Nagasaka, Hironori; Yorifuji, Tohru; Egawa, Hiroto; Inui, Ayano; Fujisawa, Tomoo; Komatsu, Haruki; Tsukahara, Hirokazu; Uemoto, Shinji; Inomata, Yukihiro

2013-07-01

Urea cycle deficient patients with prominent hyperammonemic often exhibit abnormal production of nitric oxide (NO), which reduces vascular tone, along with amino acid abnormalities. However, information related to the metabolic changes in heterozygotes of ornithine transcarbamylase deficiency (OTCD) lacking overt hyperammonemia is quite limited. We examined vascular mediators and amino acids in non-hyperammonemic heterozygotes. Twenty-four heterozygous OTCD adult females without hyperammonemic bouts, defined as non-hyperammonemic carriers, were enrolled. We measured blood amino acids constituting urea cycle and nitric oxide (NO) cycle. Blood concentrations of nitrate/nitrite (NOx) as stable NO-metabolites, asymmetric dimethylarginine (ADMA) inhibiting NO synthesis, and endothelin-1 (ET-1) raising vascular tone were also determined. NOx concentrations were significantly lower in non-hyperammonemic carriers (p < 0.01). However, ADMA and ET-1 levels in this group were comparable to those in the age-matched control group. Arginine and citrulline levels were also significantly lower in non-hyperammonemic carriers than in controls (p < 0.01). Of the 24 non-hyperammonemic carriers, 10 often developed headaches. Their daily NOx and arginine levels were significantly lower than those in headache-free carriers (p < 0.05). In three carriers receiving oral l-arginine, blood NOx concentrations were significantly higher. In two of those three, the occurrence of headaches was decreased. These results suggest that NO cycle coupling with the urea cycle is altered substantially even in non-hyperammonemic OTCD carriers, predisposing them to headaches. Copyright © 2013 Elsevier Inc. All rights reserved.

Comparative Analysis between Ecotoxicity of Nitrogen-, Phosphorus-, and Potassium-Based Fertilizers and Their Active Ingredients

PubMed Central

Simplício, Nathan de Castro Soares; Muniz, Daphne Heloísa de Freitas; Rocha, Fernanda Regina Moreira; Martins, Denis Cavalcanti; Dias, Zélia Malena Barreira; Farias, Bruno Pereira da Costa; Oliveira-Filho, Eduardo Cyrino

2016-01-01

This study aimed to analyze the ecotoxicity of nitrogen-, phosphorus-, and potassium-based compounds to organisms of two different trophic levels in order to compare the toxic effect between high-purity substances and these substances as components of fertilizers. Dilutions were made with the fertilizers’ potassium chloride, potassium nitrate, superphosphate, urea, and their equivalent reagents, to conduct assays to establish the acute lethal concentration for half of the population (LC50). Ten individuals of the benthic snail Biomphalaria glabrata and the fish Danio rerio were exposed to each concentration of tested compounds. As a result, the toxicity levels of potassium chloride, potassium nitrate, and urea were obtained for B. glabrata and D. rerio, with the fish being more susceptible to potassium chloride in the fertilizer and the snail to potassium nitrate and urea, in both commercial and reagent forms. Regarding superphosphate, no significant toxicity was found. This study concluded that among the tested substances, KNO3 and KCl were the most toxic substances and urea the least toxic. It was not possible to establish the most sensitive species since, for KCl, the fish were more susceptible to the fertilizer and the snail to the reagent, while for KNO3 the opposite was observed. PMID:29051434

Computational and Pharmacological Evaluation of Ferrocene-Based Acyl Ureas and Homoleptic Cadmium Carboxylate Derivatives for Anti-diabetic Potential.

PubMed

Bano, Shahar; Khan, Arif-Ullah; Asghar, Faiza; Usman, Muhammad; Badshah, Amin; Ali, Saqib

2017-01-01

We investigated possible anti-diabetic effect of ferrocene-based acyl ureas: 4-ferrocenyl aniline (PFA), 1-(4-chlorobenzoyl)-3-(4-ferrocenylphenyl) urea (DPC1), 1-(3-chlorobenzoyl)-3-(4-ferrocenylphenyl) urea (DMC1), 1-(2-chlorobenzoyl)-3-(4-ferrocenylphenyl) urea (DOC1) and homoleptic cadmium carboxylates: bis (diphenylacetato) cadmium (II) (DPAA), bis (4-chlorophenylacetato) cadmium (II) (CPAA), using in silico and in vivo techniques. PFA, DPC1, DMC1, DOC1, DPAA and CPAA exhibited high binding affinities (ACE ≥ -350 Kcal/mol) against targets: aldose reductase, peroxisome proliferator-activated receptor γ, 11β-hydroxysteroid dehydrogenase-1, C-alpha glucosidase and glucokinase, while showed moderate affinities (ACE ≥ -250 Kcal/mol) against N-alpha glucosidase, dipeptidyl peptidase-IV, phosphorylated-Akt, glycogen synthase kinase-3β, fructose-1,6-bisphosphatase and phosphoenolpyruvate carboxykinase, whereas revealed lower affinities (ACE < -250 Kcal/mol) vs. alpha amylase, protein tyrosine phosphatases 1B, glycogen phosphorylase and phosphatidylinositol 3 kinase. In alloxan (300 mg/Kg)-induced diabetic mice, DPAA and DPC1 (1-10 mg/Kg) at day 1, 5, 10, 15, and 20th decreased blood glucose levels, compared to diabetic control group and improved the treated animals body weight. DPAA (10 mg/Kg) and DPC1 (5 mg/Kg) in time-dependent manner (30-120 min.) enhanced tolerance of oral glucose overload in mice. DPAA and DPCI dose-dependently at 1, 5, and 10 mg/Kg decreased glycosylated hemoglobin levels in diabetic animals, as caused by metformin. These results indicate that aforementioned derivatives of ferrocene and cadmium possess anti-diabetic potential.

In vitro studies on the effect of physical cross-linking on the biological performance of aliphatic poly(urethane urea) for blood contact applications.

PubMed

Thomas, V; Kumari, T V; Jayabalan, M

2001-01-01

The effect of physical cross-linking in candidate cycloaliphatic and hydrophobic poly(urethane urea) (4,4'-methylenebis(cyclohexylisocyanate), H(12)MDI/hydroxy-terminated polybutadiene, HTPBD/hexamethylenediamine, HDA) and poly(ether urethane urea)s (H(12)MDI/HTPBD-PTMG/HDA) on the in vitro calcification and blood-material interaction was studied. All the candidate poly(urethane urea)s and poly(ether urethane urea)s elicit acceptable hemolytic activity, cytocompatibility, calcification, and blood compatibility in vitro. The studies on blood-material interaction reveal that the present poly(urethane urea)s are superior to polystyrene microtiter plates which were used for the studies on blood-material interaction. The present investigation reveals the influence of physical cross-link density on biological interaction differently with poly(urethane urea) and poly(ether urethane urea)s. The higher the physical cross-link density in the poly(urethane urea)s, the higher the calcification and consumption of WBC in whole blood. On the other hand, the higher the physical cross-link density in the poly(ether urethane urea)s, the lesser the calcification and consumption of WBC in whole blood. However a reverse of the above trend has been observed with the platelet consumption in the poly(urethane urea)s and poly(ether urethane urea)s.

Lactobacillus reuteri 100-23 modulates urea hydrolysis in the murine stomach.

PubMed

Wilson, Charlotte M; Loach, Diane; Lawley, Blair; Bell, Tracey; Sims, Ian M; O'Toole, Paul W; Zomer, Aldert; Tannock, Gerald W

2014-10-01

Comparisons of in vivo (mouse stomach) and in vitro (laboratory culture) transcriptomes of Lactobacillus reuteri strain 100-23 were made by microarray analysis. These comparisons revealed the upregulation of genes associated with acid tolerance, including urease production, in the mouse stomach. Inactivation of the ureC gene reduced the acid tolerance of strain 100-23 in vitro, and the mutant was outcompeted by the wild type in the gut of ex-Lactobacillus-free mice. Urine analysis showed that stable isotope-labeled urea, administered by gavage, was metabolized to a greater extent in Lactobacillus-free mice than animals colonized by strain 100-23. This surprising observation was associated with higher levels of urease activity and fecal-type bacteria in the stomach digesta of Lactobacillus-free mice. Despite the modulation of urea hydrolysis in the stomach, recycling of urea nitrogen in the murine host was not affected since the essential amino acid isoleucine, labeled with a stable isotope, was detected in the livers of both Lactobacillus-free and 100-23-colonized animals. Therefore, our experiments reveal a new and unexpected impact of Lactobacillus colonization on urea hydrolysis in the murine gut. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Sanitising black water by auto-thermal aerobic digestion (ATAD) combined with ammonia treatment.

PubMed

Nordin, Annika C; Vinnerås, Björn

2015-01-01

The effect of a two-step process on the concentration of pathogens and indicator microorganisms in black water (0.9-1% total solids) was studied. The treatment combined auto-thermal aerobic digestion (ATAD) and ammonia sanitisation. First, the temperature of the black water was increased through ATAD and when a targeted temperature was reached (33, 41 and 45.5 °C studied), urea was added to a 0.5% concentration (total ammonia nitrogen >2.9 g L⁻¹). Escherichia coli and Salmonella spp. were reduced to non-detectable levels within 3 days following urea addition at temperatures above 40 °C, whereas when urea was added at 33 °C E. coli was still present after 8 days. By adding urea at temperatures of 40 °C and above, a 5 log10 reduction in Enterococcus spp. and a 3 log10 reduction in Ascaris suum eggs was achieved 1 week after the addition. With combined ATAD and ammonia treatment using 0.5% ww urea added at an aerobic digestion temperature >40 °C, black water was sanitised regarding the pathogens studied in 2 weeks of total treatment time.

Lactobacillus reuteri 100-23 Modulates Urea Hydrolysis in the Murine Stomach

PubMed Central

Wilson, Charlotte M.; Loach, Diane; Lawley, Blair; Bell, Tracey; Sims, Ian M.; O'Toole, Paul W.; Zomer, Aldert

2014-01-01

Comparisons of in vivo (mouse stomach) and in vitro (laboratory culture) transcriptomes of Lactobacillus reuteri strain 100-23 were made by microarray analysis. These comparisons revealed the upregulation of genes associated with acid tolerance, including urease production, in the mouse stomach. Inactivation of the ureC gene reduced the acid tolerance of strain 100-23 in vitro, and the mutant was outcompeted by the wild type in the gut of ex-Lactobacillus-free mice. Urine analysis showed that stable isotope-labeled urea, administered by gavage, was metabolized to a greater extent in Lactobacillus-free mice than animals colonized by strain 100-23. This surprising observation was associated with higher levels of urease activity and fecal-type bacteria in the stomach digesta of Lactobacillus-free mice. Despite the modulation of urea hydrolysis in the stomach, recycling of urea nitrogen in the murine host was not affected since the essential amino acid isoleucine, labeled with a stable isotope, was detected in the livers of both Lactobacillus-free and 100-23-colonized animals. Therefore, our experiments reveal a new and unexpected impact of Lactobacillus colonization on urea hydrolysis in the murine gut. PMID:25063664

Trace level and highly selective determination of urea in various real samples based upon voltammetric analysis of diacetylmonoxime-urea reaction product on the carbon nanotube/carbon paste electrode.

PubMed

Alizadeh, Taher; Ganjali, Mohammad Reza; Rafiei, Faride

2017-06-29

In this study an innovative method was introduced for selective and precise determination of urea in various real samples including urine, blood serum, soil and water. The method was based on the square wave voltammetry determination of an electroactive product, generated during diacetylmonoxime reaction with urea. A carbon paste electrode, modified with multi-walled carbon nanotubes (MWCNTs) was found to be an appropriate electrochemical transducer for recording of the electrochemical signal. It was found that the chemical reaction conditions influenced the analytical signal directly. The calibration graph of the method was linear in the range of 1 × 10 -7 - 1 × 10 -2  mol L -1 . The detection limit was calculated to be 52 nmol L -1 . Relative standard error of the method was also calculated to be 3.9% (n = 3). The developed determination procedure was applied for urea determination in various real samples including soil, urine, plasma and water samples. Copyright © 2017 Elsevier B.V. All rights reserved.

Urea, the most abundant component in urine, cross-reacts with a commercial 8-OH-dG ELISA kit and contributes to overestimation of urinary 8-OH-dG.

PubMed

Song, Ming-Fen; Li, Yun-Shan; Ootsuyama, Yuko; Kasai, Hiroshi; Kawai, Kazuaki; Ohta, Masanori; Eguchi, Yasumasa; Yamato, Hiroshi; Matsumoto, Yuki; Yoshida, Rie; Ogawa, Yasutaka

2009-07-01

Urinary 8-OH-dG is commonly analyzed as a marker of oxidative stress. For its analysis, ELISA and HPLC methods are generally used, although discrepancies in the data obtained by these methods have often been discussed. To clarify this problem, we fractionated human urine by reverse-phase HPLC and assayed each fraction by the ELISA method. In addition to the 8-OH-dG fraction, a positive reaction was observed in the first eluted fraction. The components in this fraction were examined by the ELISA. Urea was found to be the responsible component in this fraction. Urea is present in high concentrations in the urine of mice, rats, and humans, and its level is influenced by many factors. Therefore, certain improvements, such as a correction based on urea content or urease treatment, are required for the accurate analysis of urinary 8-OH-dG by the ELISA method. In addition, performance of the ELISA at 4 degrees C reduced the recognition of urea considerably and improved the 8-OH-dG analysis.

Pseudomonas aeruginosa mutants resistant to urea inhibition of growth on acetanilide.

PubMed

Gregoriou, M; Brown, P R; Tata, R

1977-11-01

Pseudomonas aeruginosa AI 3 was able to grow in medium containing acetanilide (N-phenylacetamide) as a carbon source when NH4+ was the nitrogen source but not when urea was the nitrogen source. AIU mutants isolated from strain AI 3 grew on either medium. Urease levels in bacteria grown in the presence of urea were 10-fold lower when NH4+ or acetanilide was also in the medium, but there were no apparent differences in urease or its synthesis between strain AI 3 and mutant AIU 1N. The first metabolic step in the acetanilide utlization is catalyzed by an amidase. Amidases in several AIU strains showed altered physiochemical properties. Urea inhibited amidase in a time-dependent reaction, but the rates of the inhibitory reaction with amidases from the AIU mutants were slower than with AI 3 amidase. The purified amidase from AIU 1N showed a marked difference in its pH/activity profile from that obtained with purified AI 3 amidase. These observations indicate that the ability of strain AIU 1N and the other mutants to grow on acetanilide/urea medium is associated with a mutation in the amidase structural gene; this was confirmed for strain AIU 1N by transduction.

Simazine degradation in bioaugmented soil: urea impact and response of ammonia-oxidizing bacteria and other soil bacterial communities.

PubMed

Guo, Qingwei; Wan, Rui; Xie, Shuguang

2014-01-01

The objective of this study was to investigate the impact of exogenous urea nitrogen on ammonia-oxidizing bacteria (AOB) and other soil bacterial communities in soil bioaugmented for simazine remediation. The previously isolated simazine-degrading Arthrobacter sp. strain SD1 was used to degrade the herbicide. The effect of urea on the simazine degradation capacity of the soil bioaugmented with Arthrobacter strain SD1 was assessed using quantitative PCR targeting the s-triazine-degrading trzN and atzC genes. Structures of bacterial and AOB communities were characterized using terminal restriction fragment length polymorphism. Urea fertilizer could affect simazine biodegradation and decreased the proportion of its trzN and atzC genes in soil augmented with Arthrobacter strain SD1. Bioaugmentation process could significantly alter the structures of both bacterial and AOB communities, which were strongly affected by urea amendment, depending on the dosage. This study could provide some new insights towards s-triazine bioremediation and microbial ecology in a bioaugmented system. However, further studies are necessary in order to elucidate the impact of different types and levels of nitrogen sources on s-triazine-degraders and bacterial and AOB communities in bioaugmented soil.

Sensitivity of condition indices to changing density in a white-tailed deer population

USGS Publications Warehouse

Sams, M.G.; Lochmiller, R.L.; Qualls, C.W.; Leslie, David M.

1998-01-01

The ways in which comprehensive condition profiles, incorporating morphometric, histologic, physiologic, and diet quality indices, responded to changes in density of a white-tailed deer (Odocoileus virginianus) population were examined. Changes in these condition indices were monitored in a northeastern Oklahoma deer herd as density declined from peaks of 80 and 72 deer/km2 in 1989 and 1990 (high-density) to lows of 39 and 41 deer/km2 in 1991 and 1992 (reduced-density), respectively. Compared to a reference population (6 deer/km2), deer sampled during high-density exhibited classic signs of nutritional stress such as low body and visceral organ masses (except elevated adrenal gland mass), low fecal nitrogen levels, reduced concentrations of serum albumin, elevated serum creatinine concentrations, and a high prevalence of parasitic infections. Although density declined by one half over the 4-yr study, gross indices of condition (in particular body mass and size) remained largely unchanged. However, selected organ masses, serum albumin and non-protein nitrogen constituents, and fecal nitrogen indices reflected improvements in nutritional status with reductions in density. Many commonly used indices of deer condition (fat reserves, hematocrit, total serum protein, and blood urea nitrogen) were not responsive to fluctuations in density. ?? Wildlife Disease Association 1998.

[Effects of water conditions and controlled release urea on yield and leaf senescence physiological characteristics in summer maize.

PubMed

Li, Guang Hao; Liu, Ping Ping; Zhao, Bin; Dong, Shu Ting; Liu, Peng; Zhang, Ji Wang; Tian, Cui Xia; He, Zai Ju

2017-02-01

In an soil column experiment with Zhengdan 958 (a summer maize cultivar planted widely in China), treatments of three water levels,severe water stress W 1 which the soil moisture kept (35±5)% of the field capacity, mild water stress W 2 which was (55±5)%,normal water W 3 which was (75±5)%, and four levels of controlled release urea fertilizer (N 0 , N 1 was 150 kg N·hm -2 ,N 2 was 225 kg N·hm -2 and N 3 was 300 kg N·hm -2 ) were included to study the interactive effects of water and controlled release urea on yield and leaf senescence characteristics of summer maize. The results showed that the coupling of water and controlled release urea had significant effects on increasing yield, delaying the senescence and keeping the high efficiency of the functional leaves. Under the same nitrogen condition, yield, LAI, chlorophyll content and the activities of SOD, POD, CAT and soluble protein content in summer maize ear leaf were significantly increased with more water supplying, and the content of MDA decreased significantly. Under the condition of the same moisture, these indicators were also significantly increased with the increasing nitrogen application and MDA content was reduced significantly. However, these indicators (except MDA) of W 3 N 3 , W 3 N 2 and W 2 N 3 treatments were maintained at a higher level and the MDA content was lo-wer compared with other treatments despite the fact that there were no significant difference among these three treatments, which indicated that the interactive effects of water and controlled release urea had an important role in maintaining the function of ear leaf, delaying the leaf senescence, and was beneficial to the photosynthates production and obtaining higher yield of summer maize. Integrating the yield, LAI, chlorophyll content, various protective enzymes activity, MDA and soluble protein content, controlled release urea application rate of 225 kg N·hm -2 was the best treatment as the soil moisture content was (75±5)% of field capacity. Continuous increase in the nitrogen application could not enhance the activities of protective enzymes, oppositely, it could cause the decline of protective enzymes activities and the increase of MDA content rapidly and speed up plants translation to senescence, which was not conductive to the efficient use of nitrogen. We suggested that coupling controlled release urea application rate of 300 kg N·hm -2 with soil moisture content of (55±5)% of field capacity was optimum.

Report of 3 Patients With Urea Cycle Defects Treated With Related Living-Donor Liver Transplant.

PubMed

Özçay, Figen; Barış, Zeren; Moray, Gökhan; Haberal, Nihan; Torgay, Adnan; Haberal, Mehmet

2015-11-01

Urea cycle defects are a group of metabolic disorders caused by enzymatic disruption of the urea cycle pathway, transforming nitrogen to urea for excretion from the body. Severe cases present in early infancy with life-threatening metabolic decompensation, and these episodes of hyperammonemia can be fatal or result in permanent neurologic damage. Despite the progress in pharmacologic treatment, long-term survival is poor especially for severe cases. Liver transplant is an alternative treatment option, providing sufficient enzymatic activity and decreasing the risk of metabolic decompensation. Three patients with urea cycle defects received related living-donor liver transplants at our hospital. Patients presented with late-onset ornithine transcarbamylase deficiency, argininosuccinate lyase deficiency, and citrullinemia. Maximum pretransplant ammonia levels were between 232 and 400 μmol/L (normal range is 18-72 μmol/L), and maximum posttransplant values were 52 to 94 μmol/L. All patients stopped medical treatment and dietary protein restriction for urea cycle defects after transplant. The patient with late-onset ornithine transcarbamylase deficiency already had motor deficits related to recurrent hyperammonemia attacks pretransplant. A major improvement could not be achieved, and he is wheelchair dependent at the age of 6 years. The other 2 patients had normal motor and mental skills before transplant, which have continued 12 and 14 months after transplant. Hepatic artery thrombosis in the patient with the ornithine transcarbamylase deficiency, intraabdominal infection in the patient with argininosuccinate lyase deficiency, and posterior reversible encephalopathy syndrome in the patient with citrullinemia were early postoperative complications. Histopathologic changes in livers explanted from patients with ornithine transcarbamylase deficiency and citrullinemia were nonspecific. The argininosuccinate lyase-deficient patient had portoportal fibrosis and cirrhotic nodule formation. In conclusion, liver transplant was a lifesaving procedure for our patients. Proper timing for transplant is important because high ammonia levels may result in permanent neurologic damage; however, transplant at younger ages also may increase morbidity.

Molecular regulation of urea cycle function by the liver glucocorticoid receptor.

PubMed

Okun, Jürgen G; Conway, Sean; Schmidt, Kathrin V; Schumacher, Jonas; Wang, Xiaoyue; de Guia, Roldan; Zota, Annika; Klement, Johanna; Seibert, Oksana; Peters, Achim; Maida, Adriano; Herzig, Stephan; Rose, Adam J

2015-10-01

One of the major side effects of glucocorticoid (GC) treatment is lean tissue wasting, indicating a prominent role in systemic amino acid metabolism. In order to uncover a novel aspect of GCs and their intracellular-receptor, the glucocorticoid receptor (GR), on metabolic control, we conducted amino acid and acylcarnitine profiling in human and mouse models of GC/GR gain- and loss-of-function. Blood serum and tissue metabolite levels were determined in Human Addison's disease (AD) patients as well as in mouse models of systemic and liver-specific GR loss-of-function (AAV-miR-GR) with or without dexamethasone (DEX) treatments. Body composition and neuromuscular and metabolic function tests were conducted in vivo and ex vivo, the latter using precision cut liver slices. A serum metabolite signature of impaired urea cycle function (i.e. higher [ARG]:[ORN + CIT]) was observed in human (CTRL: 0.45 ± 0.03, AD: 1.29 ± 0.04; p < 0.001) and mouse (AAV-miR-NC: 0.97 ± 0.13, AAV-miR-GR: 2.20 ± 0.19; p < 0.001) GC/GR loss-of-function, with similar patterns also observed in liver. Serum urea levels were consistently affected by GC/GR gain- (∼+32%) and loss (∼-30%) -of-function. Combined liver-specific GR loss-of-function with DEX treatment revealed a tissue-autonomous role for the GR to coordinate an upregulation of liver urea production rate in vivo and ex vivo, and prevent hyperammonaemia and associated neuromuscular dysfunction in vivo. Liver mRNA expression profiling and GR-cistrome mining identified Arginase I (ARG1) a urea cycle gene targeted by the liver GR. The liver GR controls systemic and liver urea cycle function by transcriptional regulation of ARG1 expression.

Effects of arginine treatment on nutrition, growth and urea cycle function in seven Japanese boys with late-onset ornithine transcarbamylase deficiency.

PubMed

Nagasaka, Hironori; Yorifuji, Tohru; Murayama, Kei; Kubota, Mitsuru; Kurokawa, Keiji; Murakami, Tomoko; Kanazawa, Masaki; Takatani, Tomozumi; Ogawa, Atsushi; Ogawa, Emi; Yamamoto, Shigenori; Adachi, Masanori; Kobayashi, Kunihiko; Takayanagi, Masaki

2006-09-01

The aim of this study was to investigate the effects of arginine on nutrition, growth and urea cycle function in boys with late-onset ornithine transcarbamylase deficiency (OTCD). Seven Japanese boys with late-onset OTCD enrolled in this study resumed arginine treatment after the cessation of this therapy for a few years. Clinical presentations such as vomiting and unconsciousness, plasma amino acids and urinary orotate excretion were followed chronologically to evaluate urea cycle function and protein synthesis with and without this therapy. In addition to height and body weight, blood levels of proteins, lipids, growth hormone (GH), insulin-like growth factor-I (IGF-I) and IGF-binding protein -3 (IGFBP-3) were monitored. The frequency of hyperammonemic attacks and urinary orotate excretion decreased significantly following the resumption of arginine treatment. Despite showing no marked change in body weight, height increased gradually. Extremely low plasma arginine increased to normal levels, while plasma glutamine and alanine levels decreased considerably. Except for a slight increase in high-density lipoprotein cholesterol level, blood levels of markers for nutrition did not change. In contrast, low serum IGF-I and IGFBP-3 levels increased to age-matched control levels, and normal urinary GH secretion became greater than the level observed in the controls. Arginine treatment is able to reduces attacks of hyperammonemia in boys with late-onset OTCD and to increase their growth.

Urinary Urea, Uric Acid and Hippuric Acid as Potential Biomarkers in Multiple Sclerosis Patients.

PubMed

Atya, Hanaa B; Ali, Sahar A; Hegazy, Mohamed I; El Sharkawi, Fathia Z

2018-04-01

Urine is a proven source of metabolite biomarkers and has the potential to be a rapid, noninvasive, inexpensive, and efficient diagnostic tool for various human diseases. Despite these advantages, urine is an under-investigated source of biomarkers for multiple sclerosis (MS). The objective was to investigate the level of some urinary metabolites (urea, uric acid and hippuric acid) in patients with MS and correlate their levels to the severity of the disease, MS subtypes and MS treatment. The urine samples were collected from 73 MS patients-48 with RRMS and 25 with SPMS- and age matched 75 healthy controls. The values of urinary urea, uric acid and hippuric acid in MS patients were significantly decreased, and these metabolites in SPMS pattern showed significantly decrease than RRMS pattern. Also showed significant inverse correlation with expanded disability status scale and number of relapses. Accordingly, they may act as a potential urinary biomarkers for MS, and correlate to disease progression.

Serum Amino Acid Profiling in Citrin-Deficient Children Exhibiting Normal Liver Function During the Apparently Healthy Period.

PubMed

Miyazaki, Teruo; Nagasaka, Hironori; Komatsu, Haruki; Inui, Ayano; Morioka, Ichiro; Tsukahara, Hirokazu; Kaji, Shunsaku; Hirayama, Satoshi; Miida, Takashi; Kondou, Hiroki; Ihara, Kenji; Yagi, Mariko; Kizaki, Zenro; Bessho, Kazuhiko; Kodama, Takahiro; Iijima, Kazumoto; Yorifuji, Tohru; Matsuzaki, Yasushi; Honda, Akira

2018-04-14

Citrin (mitochondrial aspartate-glutamate transporter) deficiency causes the failures in both carbohydrate-energy metabolism and the urea cycle, and the alterations in the serum levels of several amino acids in the stages of newborn (NICCD) and adult (CTLN2). However, the clinical manifestations are resolved between the NICCD and CTLN2, but the reasons are still unclear. This study evaluated the serum amino acid profile in citrin-deficient children during the healthy stage. Using HPLC-MS/MS analysis, serum amino acids were evaluated among 20 citrin-deficient children aged 5-13 years exhibiting normal liver function and 35 age-matched healthy controls. The alterations in serum amino acids characterized in the NICCD and CTLN2 stages were not observed in the citrin-deficient children. Amino acids involved in the urea cycle, including arginine, ornithine, citrulline, and aspartate, were comparable in the citrin-deficient children to the respective control levels, but serum urea was twofold higher, suggestive of a functional urea cycle. The blood sugar level was normal, but glucogenic amino acids and glutamine were significantly decreased in the citrin-deficient children compared to those in the controls. In addition, significant increases of ketogenic amino acids, branched-chain amino acids (BCAAs), a valine intermediate 3-hydroxyisobutyrate, and β-alanine were also found in the citrin-deficient children. The profile of serum amino acids in the citrin-deficient children during the healthy stage showed different characteristics from the NICCD and CTLN2 stages, suggesting that the failures in both urea cycle function and energy metabolism might be compensated by amino acid metabolism. In the citrin-deficient children during the healthy stage, the characteristics of serum amino acids, including decrease of glucogenic amino acids, and increase of ketogenic amino acids, BCAAs, valine intermediate, and β-alanine, were found by comparison to the age-matched healthy control children, and it suggested that the characteristic alteration of serum amino acids may be resulted from compensation for energy metabolism and ammonia detoxification.

Responses of Ammonia-Oxidizing Bacterial and Archaeal Populations to Organic Nitrogen Amendments in Low-Nutrient Groundwater ▿

PubMed Central

Reed, David W.; Smith, Jason M.; Francis, Christopher A.; Fujita, Yoshiko

2010-01-01

To evaluate the potential for organic nitrogen addition to stimulate the in situ growth of ammonia oxidizers during a field scale bioremediation trial, samples collected from the Eastern Snake River Plain Aquifer in Idaho before, during, and after the addition of molasses and urea were subjected to PCR analysis of ammonia monooxygenase subunit A (amoA) genes. Ammonia-oxidizing bacteria (AOB) and archaea (AOA) were present in all of the samples tested, with AOA amoA genes outnumbering AOB amoA genes in all of the samples. Following urea addition, nitrate levels rose and bacterial amoA copy numbers increased dramatically, suggesting that urea hydrolysis stimulated nitrification. Bacterial amoA diversity was limited to two Nitrosomonas phylotypes, whereas archaeal amoA analyses revealed 20 distinct operational taxonomic units, including several that were markedly different from all previously reported sequences. Results from this study demonstrate the likelihood of stimulating ammonia-oxidizing communities during field scale manipulation of groundwater conditions to promote urea hydrolysis. PMID:20190081

Predictive values of semi-quantitative procalcitonin test and common biomarkers for the clinical outcomes of community-acquired pneumonia.

PubMed

Ugajin, Motoi; Yamaki, Kenichi; Hirasawa, Natsuko; Yagi, Takeo

2014-04-01

The semi-quantitative serum procalcitonin test (Brahms PCT-Q) is available conveniently in clinical practice. However, there are few data on the relationship between results for this semi-quantitative procalcitonin test and clinical outcomes of community-acquired pneumonia (CAP). We investigated the usefulness of this procalcitonin test for predicting the clinical outcomes of CAP in comparison with severity scoring systems and the blood urea nitrogen/serum albumin (B/A) ratio, which has been reported to be a simple but reliable prognostic indicator in our prior CAP study. This retrospective study included data from subjects who were hospitalized for CAP from August 2010 through October 2012 and who were administered the semi-quantitative serum procalcitonin test on admission. The demographic characteristics; laboratory biomarkers; microbiological test results; Pneumonia Severity Index scores; confusion, urea nitrogen, breathing frequency, blood pressure, ≥ 65 years of age (CURB-65) scale scores; and age, dehydration, respiratory failure, orientation disturbance, pressure (A-DROP) scale scores on hospital admission were retrieved from their medical charts. The outcomes were mortality within 28 days of hospital admission and the need for intensive care. Of the 213 subjects with CAP who were enrolled in the study, 20 died within 28 days of hospital admission, and 32 required intensive care. Mortality did not differ significantly among subjects with different semi-quantitative serum procalcitonin levels; however, subjects with serum procalcitonin levels ≥ 10.0 ng/mL were more likely to require intensive care than those with lower levels (P < .001). The elevation of semi-quantitative serum procalcitonin levels was more frequently observed in subjects with proven etiology, especially pneumococcal pneumonia. Using the receiver operating characteristic curves for mortality, the area under the curve was 0.86 for Pneumonia Severity Index class, 0.81 for B/A ratio, 0.81 for A-DROP, 0.80 for CURB-65, and 0.57 for semi-quantitative procalcitonin test. The semi-quantitative serum procalcitonin level on hospital admission was less predictive of mortality from CAP compared with the B/A ratio. However, the subjects with serum procalcitonin levels ≥ 10.0 ng/mL were more likely to require intensive care than those with lower levels.

Hypervolemic hypernatremia is the most common type of hypernatremia in the intensive care unit.

PubMed

Sarahian, Sanaz; Pouria, Mohammad Mehdi; Ing, Todd S; Sam, Ramin

2015-11-01

A high incidence of hypervolemic hypernatremia has been described in patients recovering from acute kidney injury (AKI) in intensive care units. However, this has been limited to only a few cases. One hundred fifty adult patients recovering from AKI in the intensive care unit of a single institution during a 6-year period, who developed hypernatremia during the course of their illness, were investigated. Serum and urine electrolytes, osmolality, urea nitrogen and creatinine were measured. The weights of these patients at the time of hypernatremia development and at presentation to the hospital were also measured. Even though the hypernatremia was mild in most patients (146-160 mEq/L), the average rise in serum sodium concentration was 14.5 ± 7.1 mEq/L. Of the 34 patients who had all urinary studies available, the average urine osmolality was 436 ± 128 mmol/kg of which 172 ± 54 mmol/L was contributed by sodium, potassium and their accompanying anion. Another 204 ± 96 mmol/L was accounted for by urea and creatinine (mainly urea). Almost all the patients had hypervolemia as evidenced by the presence of edema and an average weight gain of more than 9 ± 11 kg between the time of presentation and the onset of hypernatremia despite likely having lost muscle mass from being in the intensive care unit for several days. The weight data were available in 54 patients, and only eight of these patients had lost weight at the time of the development of hypernatremia. Hypervolemic hypernatremia is by far the most common cause of hypernatremia in patients in the intensive care unit. Even though the patients are in negative fluid balance at the time of the development of the hypernatremia, earlier saline administration has caused massive volume overload despite the ongoing losses. Post-AKI diuresis in the face of inability to maximally concentrate the urine because of renal failure often leads to mainly mild elevations in serum sodium concentration. The urine solute is mainly urea because of the often high serum urea concentrations with little electrolytes being present in the urine.

Attenuation of CCl4-Induced Oxidative Stress and Hepatonephrotoxicity by Saudi Sidr Honey in Rats.

PubMed

Al-Yahya, Mohammed; Mothana, Ramzi; Al-Said, Mansour; Al-Dosari, Mohammed; Al-Musayeib, Nawal; Al-Sohaibani, Mohammed; Parvez, Mohammad Khalid; Rafatullah, Syed

2013-01-01

The present study was undertaken to investigate the possible protective effect of Saudi Sidr honey (SSH) on carbon tetrachloride (CCl4) induced oxidative stress and liver and kidney damage in rat. Moreover, the antioxidant activity and the phenolic and flavonoidal contents were determined. The hepatorenal protective activity of the SSH was determined by assessing biochemical, hematological, and histological parameters. Serum transaminases, ALP, GGT, creatinine, bilirubin urea, uric acid, and MDA level in liver and kidney tissues were significantly elevated, and the antioxidant status of nonprotein sulfhydryls, albumin, and total protein levels in liver and kidney were declined significantly in CCl4 alone treated animals. Pretreatment with SSH and silymarin prior to the administration of CCl4 significantly prevented the increase of the serum levels of enzyme markers and reduced oxidative stress. SSH also exhibited a significant lipid-lowering effect and caused an HDL-C enhanced level in serum. The histopathological evaluation of the liver and kidney also revealed that honey protected incidence of both liver and kidney lesions. Moreover, SSH showed a strong antioxidant activity in DPPH and β -carotene-linoleic acid assays. SSH was found to contain phenolic compounds. Additionally, the SSH supplementation restored the hepatocytes viability against 2',7'-dichlorofluorescein (DCF) toxicity in ex vivo test.

Attenuation of CCl4-Induced Oxidative Stress and Hepatonephrotoxicity by Saudi Sidr Honey in Rats

PubMed Central

Al-Yahya, Mohammed; Mothana, Ramzi; Al-Said, Mansour; Al-Dosari, Mohammed; Al-Musayeib, Nawal; Al-Sohaibani, Mohammed; Parvez, Mohammad Khalid; Rafatullah, Syed

2013-01-01

The present study was undertaken to investigate the possible protective effect of Saudi Sidr honey (SSH) on carbon tetrachloride (CCl4) induced oxidative stress and liver and kidney damage in rat. Moreover, the antioxidant activity and the phenolic and flavonoidal contents were determined. The hepatorenal protective activity of the SSH was determined by assessing biochemical, hematological, and histological parameters. Serum transaminases, ALP, GGT, creatinine, bilirubin urea, uric acid, and MDA level in liver and kidney tissues were significantly elevated, and the antioxidant status of nonprotein sulfhydryls, albumin, and total protein levels in liver and kidney were declined significantly in CCl4 alone treated animals. Pretreatment with SSH and silymarin prior to the administration of CCl4 significantly prevented the increase of the serum levels of enzyme markers and reduced oxidative stress. SSH also exhibited a significant lipid-lowering effect and caused an HDL-C enhanced level in serum. The histopathological evaluation of the liver and kidney also revealed that honey protected incidence of both liver and kidney lesions. Moreover, SSH showed a strong antioxidant activity in DPPH and β-carotene-linoleic acid assays. SSH was found to contain phenolic compounds. Additionally, the SSH supplementation restored the hepatocytes viability against 2′,7′-dichlorofluorescein (DCF) toxicity in ex vivo test. PMID:23533498

Urea Hydrogen Peroxide Reduces the Numbers of Lactobacilli, Nourishes Yeast, and Leaves No Residues in the Ethanol Fermentation

PubMed Central

Narendranath, N. V.; Thomas, K. C.; Ingledew, W. M.

2000-01-01

Urea hydrogen peroxide (UHP) at a concentration of 30 to 32 mmol/liter reduced the numbers of five Lactobacillus spp. (Lactobacillus plantarum, L. paracasei, Lactobacillus sp. strain 3, L. rhamnosus, and L. fermentum) from ∼107 to ∼102 CFU/ml in a 2-h preincubation at 30°C of normal-gravity wheat mash at ∼21 g of dissolved solids per ml containing normal levels of suspended grain particles. Fermentation was completed 36 h after inoculation of Saccharomyces cerevisiae in the presence of UHP, even when wheat mash was deliberately contaminated (infected) with L. paracasei at ∼107 CFU/ml. There were no significant differences in the maximum ethanol produced between treatments when urea hydrogen peroxide was used to kill the bacteria and controls (in which no bacteria were added). However, the presence of L. paracasei at ∼107 CFU/ml without added agent resulted in a 5.84% reduction in the maximum ethanol produced compared to the control. The bactericidal activity of UHP is greatly affected by the presence of particulate matter. In fact, only 2 mmol of urea hydrogen peroxide per liter was required for disinfection when mashes had little or no particulate matter present. No significant differences were observed in the decomposition of hydrogen peroxide in normal-gravity wheat mash at 30°C whether the bactericidal agent was added as H2O2 or as urea hydrogen peroxide. NADH peroxidase activity (involved in degrading H2O2) increased significantly (P = 0.05) in the presence of 0.75 mM hydrogen peroxide (sublethal level) in all five strains of lactobacilli tested but did not persist in cells regrown in the absence of H2O2. H2O2-resistant mutants were not expected or found when lethal levels of H2O2 or UHP were used. Contaminating lactobacilli can be effectively managed by UHP, a compound which when used at ca. 30 mmol/liter happens to provide near-optimum levels of assimilable nitrogen and oxygen that aid in vigorous fermentation performance by yeast. PMID:11010858

Metformin-induced lactic acidosis: a case series.

PubMed

Silvestre, Joana; Carvalho, Susana; Mendes, Vitor; Coelho, Luis; Tapadinhas, Camila; Ferreira, Pedro; Povoa, Pedro; Ceia, Fatima

2007-10-31

Unlike other agents used in the treatment of type 2 diabetes mellitus, metformin has been shown to reduce mortality in obese patients. It is therefore being increasingly used in higher doses. The major concern of many physicians is a possible risk of lactic acidosis. The reported frequency of metformin related lactic acidosis is 0.05 per 1000 patient-years; some authors advocate that this rate is equal in those patients not taking metformin. We present two case reports of metformin-associated lactic acidosis. The first case is a 77 year old female with a past medical history of hypertension and type 2 diabetes mellitus who had recently been prescribed metformin (3 g/day), perindopril and acetylsalicylic acid. She was admitted to the emergency department two weeks later with abdominal pain and psychomotor agitation. Physical examination revealed only signs of poor perfusion. Laboratory evaluation revealed hyperkalemia, elevated creatinine and blood urea nitrogen and mild leukocytosis. Arterial blood gases showed severe lactic acidemia. She was admitted to the intensive care unit. Vasopressor and ventilatory support was initiated and continuous venovenous hemodiafiltration was instituted. Twenty-four hours later, full clinical recovery was observed, with return to a normal serum lactate level. The patient was discharged from the intensive care unit on the sixth day. The second patient is a 69 year old male with a past medical history of hypertension, type 2 diabetes mellitus and ischemic heart disease who was on metformin (4 g/day), glycazide, acetylsalicylic acid and isosorbide dinitrate. He was admitted to the emergency department in shock with extreme bradycardia. Initial evaluation revealed severe lactic acidosis and elevated creatinine and urea. The patient was admitted to the Intensive Care Unit and commenced on continuous venovenous hemodiafiltration in addition to other supportive measures. A progressive recovery was observed and he was discharged from the intensive care unit on the seventh day. We present two case reports of severe lactic acidosis most probably associated with high doses of metformin in patients with no known contraindications for metformin prescription. In both patients no other condition was identified to cause such severe lactic acidosis. Although controversial, lactic acidosis should be considered in patients taking metformin.

A simple apparatus for measuring the blood urea, manufactured by Dr. Luigj Benusi in 1943 in Albania.

PubMed

Tartari, Flamur; Buzo, Stiliano; Vyshka, Gentian

2009-01-01

The apparatus invented by Dr. Luigj Benusi in 1943, in Tirana, was a practical application of the Kowarsky technique and Ambard laws, helping in determining blood urea levels and very important to a variety of diseases, mainly kidney disorders. The apparatus was invented and prepared from very simple laboratory materials, such as glasses, test tubes, corks and volumetric cylinders. Technologically, it was based upon the determination of blood urea through hypobromite, and, among the advantages of the apparatus of Benusi, were its extreme simplicity, the smaller amount of blood needed for producing results (2 milliliters), as well as an easiest way to clean up and to manage the apparatus from a practical point of everyday use.

Co-encapsulation of enzyme and sensitive dye as a tool for fabrication of microcapsule based sensor for urea measuring.

PubMed

Kazakova, Lyubov I; Shabarchina, Lyudmila I; Sukhorukov, Gleb B

2011-06-21

Enzyme based micron sized sensing system with optical readout was fabricated by co-encapsulation of urease and dextran couple with pH sensitive dye SNARF-1 into polyelectrolyte multilayer capsules. Co-precipitation of calcium carbonate, urease and dextran followed up by multilayer film coating and Ca-extracting by EDTA resulted in the formation of 3.5-4 micron capsules, what enable the calibrated fluorescence response to urea in concentration range from 10(-6) to 10(-1) M. The presence of urea can be monitored on a single capsule level as illustrated by confocal fluorescent microscopy. Variations in urease:dye ratio in capsules, applicability and limits of use of that type multi-component microencapsulated sensors are discussed.

The combined effects of urea application and simulated acid rain on soil acidification and microbial community structure.

PubMed

Liu, Xingmei; Zhou, Jian; Li, Wanlu; Xu, Jianming; Brookes, Philip C

2014-05-01

Our aim was to test the effects of simulated acid rain (SAR) at different pHs, when applied to fertilized and unfertilized soils, on the leaching of soil cations (K, Ca, Mg, Na) and Al. Their effects on soil pH, exchangeable H(+) and Al(3+) and microbial community structure were also determined. A Paleudalfs soil was incubated for 30 days, with and without an initial application of urea (200 mg N kg(-1)soil) as nitrogen (N) fertilizer. The soil was held in columns and leached with SAR at three pH levels. Six treatments were tested: SAR of pH 2.5, 4.0 and 5.6 leaching on unfertilized soil (T1, T2 and T3), and on soils fertilized with urea (T4, T5 and T6). Increasing acid inputs proportionally increased cation leaching in both unfertilized and fertilized soils. Urea application increased the initial Ca and Mg leaching, but had no effect on the total concentrations of Ca, Mg and K leached. There was no significant difference for the amount of Na leached between the different treatments. The SAR pH and urea application had significant effects on soil pH, exchangeable H(+) and Al(3+). Urea application, SAR treated with various pH, and the interactions between them all had significant impacts on total phospholipid fatty acids (PLFAs). The highest concentration of total PLFAs occurred in fertilized soils with SAR pH5.6 and the lowest in soils leached with the lowest SAR pH. Soils pretreated with urea then leached with SARs of pH 4.0 and 5.6 had larger total PLFA concentrations than soil without urea. Bacterial, fungal, actinomycete, Gram-negative and Gram-positive bacterial PLFAs had generally similar trends to total PLFAs.

Localization and regulation of a facilitative urea transporter in the kidney of the red-eared slider turtle (Trachemys scripta elegans).

PubMed

Uchiyama, Minoru; Kikuchi, Ryosuke; Konno, Norifumi; Wakasugi, Tatsuya; Matsuda, Kouhei

2009-01-01

Urea is the major excretory end product of nitrogen metabolism in most chelonian reptiles. In the present study, we report the isolation of a 1632 base pair cDNA from turtle kidney with one open reading frame putatively encoding a 403-residue protein, the turtle urea transporter (turtle UT). The first cloned reptilian UT has high homology with UTs (facilitated urea transporters) cloned from vertebrates, and most closely resembles the UT-A subfamily. Injection of turtle UT cRNA into Xenopus oocytes induced a 6-fold increase in [(14)C]urea uptake that was inhibited by phloretin. The turtle UT mRNA expression and tissue distribution were examined by RT-PCR with total RNA from various tissues. Expression of turtle UT mRNA was restricted to the kidney, and no signal was detected in the other tissues, such as brain, heart, alimentary tract and urinary bladder. An approximately 58 kDa protein band was detected in membrane fractions of the kidney by western blot using an affinity-purified antibody that recognized turtle UT expressed in Xenopus oocytes. In an immunohistochemical study using the anti-turtle UT antibody, UT-immunopositive cells were observed along the distal tubule but not in the collecting duct. In turtles under dry conditions, plasma osmolality and urea concentration increased, and using semi-quantitative RT-PCR the UT mRNA expression level in the kidney was found to increase 2-fold compared with control. The present results, taken together, suggest that the turtle UT probably contributes to urea transport in the distal tubule segments of the kidney in response to hyperosmotic stress under dry conditions.

Aberrant expression and distribution of enzymes of the urea cycle and other ammonia metabolizing pathways in dogs with congenital portosystemic shunts.

PubMed

van Straten, Giora; van Steenbeek, Frank G; Grinwis, Guy C M; Favier, Robert P; Kummeling, Anne; van Gils, Ingrid H; Fieten, Hille; Groot Koerkamp, Marian J A; Holstege, Frank C P; Rothuizen, Jan; Spee, Bart

2014-01-01

The detoxification of ammonia occurs mainly through conversion of ammonia to urea in the liver via the urea cycle and glutamine synthesis. Congenital portosystemic shunts (CPSS) in dogs cause hyperammonemia eventually leading to hepatic encephalopathy. In this study, the gene expression of urea cycle enzymes (carbamoylphosphate synthetase (CPS1), ornithine carbamoyltransferase (OTC), argininosuccinate synthetase (ASS1), argininosuccinate lyase (ASL), and arginase (ARG1)), N-acetylglutamate synthase (NAGS), Glutamate dehydrogenase (GLUD1), and glutamate-ammonia ligase (GLUL) was evaluated in dogs with CPSS before and after surgical closure of the shunt. Additionally, immunohistochemistry was performed on urea cycle enzymes and GLUL on liver samples of healthy dogs and dogs with CPSS to investigate a possible zonal distribution of these enzymes within the liver lobule and to investigate possible differences in distribution in dogs with CPSS compared to healthy dogs. Furthermore, the effect of increasing ammonia concentrations on the expression of the urea cycle enzymes was investigated in primary hepatocytes in vitro. Gene-expression of CPS1, OTC, ASL, GLUD1 and NAGS was down regulated in dogs with CPSS and did not normalize after surgical closure of the shunt. In all dogs GLUL distribution was localized pericentrally. CPS1, OTC and ASS1 were localized periportally in healthy dogs, whereas in CPSS dogs, these enzymes lacked a clear zonal distribution. In primary hepatocytes higher ammonia concentrations induced mRNA levels of CPS1. We hypothesize that the reduction in expression of urea cycle enzymes, NAGS and GLUD1 as well as the alterations in zonal distribution in dogs with CPSS may be caused by a developmental arrest of these enzymes during the embryonic or early postnatal phase.

Aberrant Expression and Distribution of Enzymes of the Urea Cycle and Other Ammonia Metabolizing Pathways in Dogs with Congenital Portosystemic Shunts

PubMed Central

van Straten, Giora; van Steenbeek, Frank G.; Grinwis, Guy C. M.; Favier, Robert P.; Kummeling, Anne; van Gils, Ingrid H.; Fieten, Hille; Groot Koerkamp, Marian J. A.; Holstege, Frank C. P.; Rothuizen, Jan; Spee, Bart

2014-01-01

The detoxification of ammonia occurs mainly through conversion of ammonia to urea in the liver via the urea cycle and glutamine synthesis. Congenital portosystemic shunts (CPSS) in dogs cause hyperammonemia eventually leading to hepatic encephalopathy. In this study, the gene expression of urea cycle enzymes (carbamoylphosphate synthetase (CPS1), ornithine carbamoyltransferase (OTC), argininosuccinate synthetase (ASS1), argininosuccinate lyase (ASL), and arginase (ARG1)), N-acetylglutamate synthase (NAGS), Glutamate dehydrogenase (GLUD1), and glutamate-ammonia ligase (GLUL) was evaluated in dogs with CPSS before and after surgical closure of the shunt. Additionally, immunohistochemistry was performed on urea cycle enzymes and GLUL on liver samples of healthy dogs and dogs with CPSS to investigate a possible zonal distribution of these enzymes within the liver lobule and to investigate possible differences in distribution in dogs with CPSS compared to healthy dogs. Furthermore, the effect of increasing ammonia concentrations on the expression of the urea cycle enzymes was investigated in primary hepatocytes in vitro. Gene-expression of CPS1, OTC, ASL, GLUD1 and NAGS was down regulated in dogs with CPSS and did not normalize after surgical closure of the shunt. In all dogs GLUL distribution was localized pericentrally. CPS1, OTC and ASS1 were localized periportally in healthy dogs, whereas in CPSS dogs, these enzymes lacked a clear zonal distribution. In primary hepatocytes higher ammonia concentrations induced mRNA levels of CPS1. We hypothesize that the reduction in expression of urea cycle enzymes, NAGS and GLUD1 as well as the alterations in zonal distribution in dogs with CPSS may be caused by a developmental arrest of these enzymes during the embryonic or early postnatal phase. PMID:24945279

Metabolic and thyroidal response in air-breathing perch (Anabas testudineus) to water-borne kerosene.

PubMed

Peter, Valsa S; Joshua, Elizabeth K; Wendelaar Bonga, Sjoerd E; Peter, M C Subhash

2007-01-01

To address the physiological compensatory adaptations in air-breathing fish to a toxicant, we studied the metabolite pattern, serum and liver enzymes and thyroidal response in a tropical air-breathing perch, Anabas testudineus (kept at 30 degrees C in a 12-h L:D cycle) after exposing the fish for 48h to the water-soluble fraction of kerosene. The concentrations of serum glucose (P <0.05), triglycerides (P <0.01) and liver total protein (P <0.05) were significantly increased in kerosene-exposed fish. The serum urea level, however, remained unaffected. A significant (P <0.05) increase in liver RNA occurred without changing the liver DNA concentration. Kerosene exposure decreased the level of aspartate aminotransferase activities in serum (P <0.001) and liver (P <0.05) but it increased (P <0.05) the liver alanine aminotransferase activity without changing its activity in serum. The levels of serum (P <0.01) and liver (P <0.001) lactate dehydrogenase activity were declined and the serum (P <0.05) and liver (P <0.05) alkaline phosphatase activity levels were elevated in kerosene-treated fish. The nominated levels (3.33-6.66ml/L) of kerosene significantly (P <0.01) elevated the thyroxine (T(4)) titre, and reduced (P <0.05) the triiodothyronine (T(3)) titre. The fish pretreated with either T(3) or T(4) and exposed to kerosene had a metabolic and thyroidal response that differed from that in control fish treated with kerosene: no rise in serum glucose was observed, nor in triglycerides, total protein and RNA in the liver, whereas declined levels of T(4) and T(3) were observed. The upregulation of the thyroid along with the marked metabolite changes point to a positive involvement of thyroid in energy metabolism during kerosene exposure. This is consistent with the hypothesis that the fish thyroid responds to the action of petroleum products and influences the metabolic homeostasis of this air-breathing fish.

Replacing alfalfa silage with tannin-containing birdsfoot trefoil silage in total mixed rations for lactating dairy cows.

PubMed

Broderick, G A; Grabber, J H; Muck, R E; Hymes-Fecht, U C

2017-05-01

Two lactation trials were conducted comparing the feeding value of silages made from birdsfoot trefoil (BFT, Lotus corniculatus L.) that had been selected for low (BFTL), medium (BFTM), and high (BFTH) levels of condensed tannins (CT) to an alfalfa silage (AS) when fed as the principal forage in total mixed rations. Diets also included corn silage, high-moisture shelled corn, soybean meal, soy hulls, and supplemental fat. In trial 1, 32 lactating Holstein cows were blocked by days in milk, assigned to treatment sequences in 8 balanced 4 × 4 Latin squares, and fed 50% dietary dry matter from AS or 1 of 3 BFT silages containing 0.6, 1.2, or 1.7% CT. Diets averaged 17.5 to 19.5% crude protein and 26% neutral detergent fiber on a dry matter basis. Data were collected over the last 2 wk of each 4-wk period. Intakes were 1.3 to 2.8 kg of dry matter/d greater on BFT than on AS and cows gained 0.5 kg of body weight/d on BFT diets while losing 0.14 kg of body weight/d on the AS diet; this resulted in greater milk per dry matter intake (DMI) on AS. Linear effects indicated true protein yield and milk urea nitrogen declined with increasing CT concentration and quadratic effects indicated DMI, energy-corrected milk, and fat yield were increased at intermediate CT concentration. True protein yield and apparent N-efficiency were greater, and milk urea nitrogen lower, on all BFT diets than on AS. In trial 2, 50 lactating Holstein cows were fed a covariate AS diet for 2 wk and then blocked by parity and days in milk and randomly assigned to 1 of 5 diets that were fed continuously for 12 wk. Diets contained (dry matter basis) 48% AS, 16% AS plus 32% of 1 of 3 BFT silages with 0.5, 0.8, or 1.5% CT, or 48% of an equal mixture of each BFT silage. Diets averaged 16.5% crude protein and 30% neutral detergent fiber. Intake and milk yield tended to be lower on AS than BFT, but body weight gains averaged 0.6 kg/d on all diets. Cows fed any of the BFT silages had reduced milk urea nitrogen and ruminal ammonia and reduced urinary N excretion. Feeding the BFT mixture reduced concentrations of milk true protein and milk urea nitrogen and depressed apparent nutrient digestibility. Among diets containing the individual BFT silages, linear reductions in DMI and yield of milk, fat, true protein, lactose, and SNF were observed with increasing CT concentration. By contrast, a previous trial with the same BFT populations showed that substituting BFTH silage containing 1.6% CT for AS in rations containing 60% silage dry matter had no effect on intake, increased yield of milk, energy-corrected milk and milk components, elevated protein use-efficiency, but with a more modest reduction in milk urea nitrogen and urinary N excretion. Silage analyses suggested that the inconsistent responses among trials were related to growth environment or ensiling effects that altered tannin-protein interactions in BFT silage. Differences in diet formulation among trials may have also influenced responses. Results from the current and previous trials indicate further work is needed to identify optimum tannin levels in forages. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Nephro-protective action of P. santalinus against alcohol-induced biochemical alterations and oxidative damage in rats.

PubMed

Bulle, Saradamma; Reddy, Vaddi Damodara; Hebbani, Ananda Vardhan; Padmavathi, Pannuru; Challa, Chandrasekhar; Puvvada, Pavan Kumar; Repalle, Elisha; Nayakanti, Devanna; Aluganti Narasimhulu, Chandrakala; Nallanchakravarthula, Varadacharyulu

2016-12-01

The present study investigated the antioxidant potential of P. santalinus heartwood methanolic extract (PSE) against alcohol-induced nephro-toxicity. The results indicated an increase in the concentration of kidney damage plasma markers, urea and creatinine with a concomitant decrease in the concentration of uric acid in alcohol-administered rats. A significant decrease in plasma electrolytes and mineral levels with increased kidney thiobarbituric acid reactive substances (TBARS) and nitric oxide (NOx) levels was also observed. PSE treatment to alcohol-administered rats effectively prevented the elevation in TBARS and NOx levels. Decreased activity of Na + /K + -ATPase in alcohol administered rats was brought to near normal levels with treatment of PSE. Chronic alcohol consumption affects antioxidant enzymatic activity and reabsorption function of the kidney which is evident from the decreased level of GSH as well as the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione s-transferase (GST). However, treatment with PSE to alcohol-administered rats significantly enhanced these enzymatic activities and reduced glutathione (GSH) content close to normal level. Alcohol-induced organ damage was evident from morphological changes in the kidney. Nevertheless, administration of PSE effectively restored these morphological changes to normal. The flavonoid and tannoid compounds might have protective activity against alcohol-induced oxidative/nitrosative stress mediated kidney damage. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Urea transporter UT-B deletion induces DNA damage and apoptosis in mouse bladder urothelium.

PubMed

Dong, Zixun; Ran, Jianhua; Zhou, Hong; Chen, Jihui; Lei, Tianluo; Wang, Weiling; Sun, Yi; Lin, Guiting; Bankir, Lise; Yang, Baoxue

2013-01-01

Previous studies found that urea transporter UT-B is abundantly expressed in bladder urothelium. However, the dynamic role of UT-B in bladder urothelial cells remains unclear. The objective of this study is to evaluate the physiological roles of UT-B in bladder urothelium using UT-B knockout mouse model and T24 cell line. Urea and NO measurement, mRNA expression micro-array analysis, light and transmission electron microscopy, apoptosis assays, DNA damage and repair determination, and intracellular signaling examination were performed in UT-B null bladders vs wild-type bladders and in vitro T24 epithelial cells. UT-B was highly expressed in mouse bladder urothelium. The genes, Dcaf11, MCM2-4, Uch-L1, Bnip3 and 45 S pre rRNA, related to DNA damage and apoptosis were significantly regulated in UT-B null urothelium. DNA damage and apoptosis highly occurred in UT-B null urothelium. Urea and NO levels were significantly higher in UT-B null urothelium than that in wild-type, which may affect L-arginine metabolism and the intracellular signals related to DNA damage and apoptosis. These findings were consistent with the in vitro study in T24 cells that, after urea loading, exhibited cell cycle delay and apoptosis. UT-B may play an important role in protecting bladder urothelium by balancing intracellular urea concentration. Disruption of UT-B function induces DNA damage and apoptosis in bladder, which can result in bladder disorders.

Urea Transporter UT-B Deletion Induces DNA Damage and Apoptosis in Mouse Bladder Urothelium

PubMed Central

Zhou, Hong; Chen, Jihui; Lei, Tianluo; Wang, Weiling; Sun, Yi; Lin, Guiting; Bankir, Lise; Yang, Baoxue

2013-01-01

Background Previous studies found that urea transporter UT-B is abundantly expressed in bladder urothelium. However, the dynamic role of UT-B in bladder urothelial cells remains unclear. The objective of this study is to evaluate the physiological roles of UT-B in bladder urothelium using UT-B knockout mouse model and T24 cell line. Methodology/Principal Findings Urea and NO measurement, mRNA expression micro-array analysis, light and transmission electron microscopy, apoptosis assays, DNA damage and repair determination, and intracellular signaling examination were performed in UT-B null bladders vs wild-type bladders and in vitro T24 epithelial cells. UT-B was highly expressed in mouse bladder urothelium. The genes, Dcaf11, MCM2-4, Uch-L1, Bnip3 and 45 S pre rRNA, related to DNA damage and apoptosis were significantly regulated in UT-B null urothelium. DNA damage and apoptosis highly occurred in UT-B null urothelium. Urea and NO levels were significantly higher in UT-B null urothelium than that in wild-type, which may affect L-arginine metabolism and the intracellular signals related to DNA damage and apoptosis. These findings were consistent with the in vitro study in T24 cells that, after urea loading, exhibited cell cycle delay and apoptosis. Conclusions/Significance UT-B may play an important role in protecting bladder urothelium by balancing intracellular urea concentration. Disruption of UT-B function induces DNA damage and apoptosis in bladder, which can result in bladder disorders. PMID:24204711

Arginase activity, urea, and hydroxyproline concentration are reduced in keratoconus keratocytes.

PubMed

Stachon, Tanja; Kolev, Krasimir; Flaskó, Zsuzsa; Seitz, Berthold; Langenbucher, Achim; Szentmáry, Nóra

2017-01-01

Keratoconus (KC) is a disease characterized by thinning and deformation of the cornea, but its etiology remains unknown. Seventy percent of the corneal stroma consists of collagen, which is composed of three intertwined polypeptide chains with glycine-hydroxyproline-proline repeats along their sequence. Arginase is a cytoplasmatic enzyme and catalyzes the conversion of arginine to urea and ornithine, which serves as a precursor for the endogenous synthesis of proline and hydroxyproline. The purpose of this study was to analyze arginase activity, as well as collagen and urea formation in normal and KC-keratocytes and to determine the impact of urea on keratocyte viability and proliferation in vitro. Primary human keratocytes were isolated by digestion in collagenase (1.0 mg/mL) from surgically removed corneas of eight keratoconus patients and eight normal human corneal buttons and cultured in DMEM/Ham's F12 medium supplemented with 5 % fetal calf serum. Arginase activity and urea concentration were measured in cell-lysates, hydroxyproline concentration in supernatant of cultured keratocytes using colorimetric assay. Cell viability and cell proliferation of cultured keratocytes were assessed after treatment with urea at concentrations up to10 mM for 24 h using assays for metabolic activity and DNA replication. Arginase activity and urea concentration in KC-keratocytes decreased by about 50 % compared to normal keratocytes (p = 0.003 and p = 0.008). Hydroxyproline synthesized by cultured KC-keratocytes was also approximately 50 % less compared to normal keratocytes (p = 0.02) and this difference decreased following treatment with 5.0 or 10.0 mM urea (p = 0.02; 0.03), without any change in cell viability (p > 0.09). However, the urea treatment increased modestly (by 20 %) the proliferation rate of KC-keratocytes (p = 0.04; 0.04; 0.04), without any effect on normal cultured keratocytes (p > 0.09). We identified suppressed arginase activity in the metabolic program of cultured keratoconus keratocytes. The level of urea, as one product of the enzyme arginase was also decreased. This results in impaired collagen synthesis, evidenced in the culture by reduced hydroxyproline concentration. In addition, our data showed that the other product of the arginase reaction, urea supports the proliferation of KC-keratocytes, without changes in their viability. The metabolic reprogramming of keratoconus keratocytes and its impact on development of a clinically detectable keratoconus disease has to be further analyzed.

Comparison of clinical associations and laboratory abnormalities in children with moderate and severe dehydration.

PubMed

Hayajneh, Wail A; Jdaitawi, Hussein; Al Shurman, Abdullah; Hayajneh, Yaseen A

2010-03-01

To search for possible early clinical associations and laboratory abnormalities in children with severe dehydration in northern Jordan. We prospectively evaluated 251 children with acute gastroenteritis. Dehydration assessment was done following a known clinical scheme. Probable clinical associations and laboratory abnormalities were examined against the preassigned dehydration status. Children with severe dehydration had significantly more hypernatremia and hyperkalemia, less isonatremia, and higher mean levels of urea, creatinine, and glucose (P < 0.005). Receiver operating characteristic curves showed statistically significant area under the curve values for laboratory variables. These area under the curve values were 0.991 (95% confidence interval [CI] 0.980-1.001) for serum urea, 0.862 (95% CI 0.746-0.978) for sodium, 0.850 (95% CI 0.751-0.949) for creatinine, 0.69 (95% CI 0.555-0.824) for potassium, and 0.684 (95% CI 0.574-0.795) for glucose (P < 0.05 for all). Certain independent serum cutoff levels of urea, creatinine, sodium, glucose, and potassium had high negative predictive value (100%), whereas other cutoff values for each, except potassium, had high positive predictive value (100%) for severe dehydration. Historic clinical characteristics of patients did not correlate to dehydration degree. Serum urea, creatinine, sodium, potassium, and glucose were useful independently in augmenting clinical examination to diagnose the degree of dehydration status among children presenting with gastroenteritis. Serum urea performed the best among all. On the contrary, none of the examined historical clinical patterns could be correlated to the dehydration status. Larger and multicenter studies are needed to validate our results and to examine their impact on final outcomes.

In vitro gas production in rumen fluid of buffalo as affected by urea-calcium mixture in high-quality feed block.

PubMed

Cherdthong, Anusorn; Wanapat, Metha

2014-04-01

This study aimed to determine the effect of urea-calcium sulphate mixture (U-cas) levels in high-quality feed block (HQFB) on ruminal digestibility, fermentation and gas kinetics in rumen fluid of swamp buffalo by using in vitro techniques. The treatments were seven levels of U-cas incorporated in HQFB at 0, 3, 6, 9, 12, 15 and 18% and the experimental design was a completely randomized design. Gas production rate constants for the insoluble fraction, potential extent of gas and cumulative gas were linearly increased with increasing levels of U-cas in HQFB. The in vitro dry matter digestibility, in vitro organic matter digestibility, true digestibility and microbial mass were altered by treatments and were greatest at 18% U-cas supplementation. Concentrations of propionate were linearly increased with increasing levels of U-cas and was highest with U-cas supplementation at 18%. The NH3 -N concentration was highest when urea was added in the HQFB while NH3 -N concentration tended to be reduced with increasing level of U-cas. The findings suggest supplementation of 18% U-cas in HQFB improves kinetics of gas production, rumen fermentation, digestibility and microbial mass as well as controlling the rate of N degradation in the rumen of swamp buffalo. © 2014 Japanese Society of Animal Science.

Effect of Microbial Interaction on Urea Metabolism in Chinese Liquor Fermentation.

PubMed

Wu, Qun; Lin, Jianchun; Cui, Kaixiang; Du, Rubin; Zhu, Yang; Xu, Yan

2017-12-20

Urea is the primary precursor of the carcinogen ethyl carbamate in fermented foods. Understanding urea metabolism is important for controlling ethyl carbamate production. Using Chinese liquor as a model system, we used metatranscriptome analysis to investigate urea metabolism in spontaneous food fermentation processes. Saccharomyces cerevisiae was dominant in gene transcription for urea biosynthesis and degradation. Lysinibacillus sphaericus was dominant for urea degradation. S. cerevisiae degraded 18% and L. sphaericus degraded 13% of urea in their corresponding single cultures, whereas they degraded 56% of urea in coculture after 12 h. Compared to single cultures, transcription of CAR1, DAL2, and argA, which are related to urea biosynthesis, decreased by 51, 36, and 69% in coculture, respectively. Transcription of DUR1 and ureA, which are related to urea degradation, increased by 227 and 70%, respectively. Thus, coexistence of the two strains promoted degradation of urea via transcriptional regulation of genes related to urea metabolism.

Pseudomonas aeruginosa mutants resistant to urea inhibition of growth on acetanilide.

PubMed Central

Gregoriou, M; Brown, P R; Tata, R

1977-01-01

Pseudomonas aeruginosa AI 3 was able to grow in medium containing acetanilide (N-phenylacetamide) as a carbon source when NH4+ was the nitrogen source but not when urea was the nitrogen source. AIU mutants isolated from strain AI 3 grew on either medium. Urease levels in bacteria grown in the presence of urea were 10-fold lower when NH4+ or acetanilide was also in the medium, but there were no apparent differences in urease or its synthesis between strain AI 3 and mutant AIU 1N. The first metabolic step in the acetanilide utlization is catalyzed by an amidase. Amidases in several AIU strains showed altered physiochemical properties. Urea inhibited amidase in a time-dependent reaction, but the rates of the inhibitory reaction with amidases from the AIU mutants were slower than with AI 3 amidase. The purified amidase from AIU 1N showed a marked difference in its pH/activity profile from that obtained with purified AI 3 amidase. These observations indicate that the ability of strain AIU 1N and the other mutants to grow on acetanilide/urea medium is associated with a mutation in the amidase structural gene; this was confirmed for strain AIU 1N by transduction. PMID:410788

[Effect of DMPP on inorganic nitrogen runoff loss from vegetable soil].

PubMed

Yu, Qiao-Gang; Fu, Jian-Rong; Ma, Jun-Wei; Ye, Jing; Ye, Xue-Zhu

2009-03-15

The effect of urea with 1% 3,4-dimethyl pyrazole phosphate (DMPP) on inorganic nitrogen runoff loss from agriculture field was determined in an undisturbed vegetable soil by using the simulated artificial rainfall method. The results show that, during the three simulated artificial rainfall period, the ammonium nitrogen content in the runoff water is increased 1.42, 2.82 and 1.95 times with the DMPP application treatment compared to regular urea treatment, respectively. In the urea with DMPP addition treatment, the nitrate nitrogen content is decreased 70.2%, 59.7% and 52.1% in the three simulated artificial rainfall runoff water, respectively. The nitrite nitrogen content is also decreased 98.7%, 90.6% and 85.6% in the three simulated artificial rainfall runoff water, respectively. The nitrate nitrogen and nitrite nitrogen runoff loss are greatly declined with the DMPP addition in the urea. Especially the nitrite nitrogen is in a significant low level and is near to the treatment with no fertilizer application. The inorganic nitrogen runoff loss is declined by 39.0% to 44.8% in the urea with DMPP addition treatment. So DMPP could be used as an effective nitrification inhibitor to control the soil ammonium oxidation, decline the nitrogen runoff loss, lower the nitrogen transformation risk to the waterbody and be beneficial for the ecological environment.

Metabolites related to renal function, immune activation, and carbamylation are associated with muscle composition in older adults.

PubMed

Lustgarten, Michael S; Fielding, Roger A

2017-12-15

Reduced skeletal muscle density in older adults is associated with insulin resistance, decreased physical function, and an increased all-cause mortality risk. To elucidate mechanisms that may underlie the maintenance of skeletal muscle density, we conducted a secondary analysis of previously published muscle composition and serum metabolomic data in 73 older adults (average age, 78y). Multivariable-adjusted linear regression was used to examine associations between 321 metabolites with muscle composition, defined as the ratio between normal density (NDM) with low density (LDM) thigh muscle cross sectional area (NDM/LDM). Sixty metabolites were significantly (p≤0.05 and q<0.30) associated with NDM/LDM. Decreased renal function and the immune response have been previously linked with reduced muscle density, but the mechanisms underlying these connections are less clear. Metabolites that were significantly associated with muscle composition were then tested for their association with circulating markers of renal function (blood urea nitrogen, creatinine, uric acid), and with the immune response (neutrophils/lymphocytes) and activation (kynurenine/tryptophan). 43 significant NDM/LDM metabolites (including urea) were co-associated with at least 1 marker of renal function; 23 of these metabolites have been previously identified as uremic solutes. The neutrophil/lymphocyte ratio was significantly associated with NDM/LDM (β±SE: -0.3±0.1, p=0.01, q=0.04). 35 significant NDM/LDM metabolites were co-associated with immune activation. Carbamylation (defined as homocitrulline/lysine) was identified as a pathway that may link renal function and immune activation with muscle composition, as 29 significant NDM/LDM metabolites were co-associated with homocitrulline/lysine, with at least 2 markers of renal function, and with kynurenine/tryptophan. When considering that elevated urea and uremic metabolites have been linked with an increased systemic microbial burden, that antimicrobial defense can be reduced in the presence of carbamylation, and that adipocytes can promote host defense, we propose the novel hypothesis that the age-related increase in adipogenesis within muscle may be a compensatory antimicrobial response to protect against an elevated microbial burden. Copyright © 2017 Elsevier Inc. All rights reserved.

Is the alkaline tide a signal to activate metabolic or ionoregulatory enzymes in the dogfish shark (Squalus acanthias)?

PubMed

Wood, Chris M; Kajimura, Makiko; Mommsen, Thomas P; Walsh, Patrick J

2008-01-01

Experimental metabolic alkalosis is known to stimulate whole-animal urea production and active ion secretion by the rectal gland in the dogfish shark. Furthermore, recent evidence indicates that a marked alkaline tide (systemic metabolic alkalosis) follows feeding in this species and that the activities of the enzymes of the ornithine-urea cycle (OUC) for urea synthesis in skeletal muscle and liver and of energy metabolism and ion transport in the rectal gland are increased at this time. We therefore evaluated whether alkalosis and/or NaCl/volume loading (which also occurs with feeding) could serve as a signal for activation of these enzymes independent of nutrient loading. Fasted dogfish were infused for 20 h with either 500 mmol L(-1) NaHCO3 (alkalosis + volume expansion) or 500 mmol L(-1) NaCl (volume expansion alone), both isosmotic to dogfish plasma, at a rate of 3 mL kg(-1) h(-1). NaHCO3 infusion progressively raised arterial pH to 8.28 (control = 7.85) and plasma [HCO3-] to 20.8 mmol L(-1) (control = 4.5 mmol L(-1)) at 20 h, with unchanged arterial P(CO2), whereas NaCl/volume loading had no effect on blood acid-base status. Rectal gland Na+,K+-ATPase activity was increased 50% by NaCl loading and more than 100% by NaHCO3 loading, indicating stimulatory effects of both volume expansion and alkalosis. Rectal gland lactate dehydrogenase activity was elevated 25% by both treatments, indicating volume expansion effects only, whereas neither treatment increased the activities of the aerobic enzymes citrate synthase, NADP-isocitrate dehydrogenase, or the ketone body-utilizing enzyme beta-hydroxybutyrate dehydrogenase in the rectal gland or liver. The activity of ornithine-citrulline transcarbamoylase in skeletal muscle was doubled by NaHCO3 infusion, but neither treatment altered the activities of other OUC-related enzymes (glutamine synthetase, carbamoylphosphate synthetase III). We conclude that both the alkaline tide and salt loading/volume expansion act as signals to activate some but not all of the elevated metabolic pathways and ionoregulatory mechanisms needed during processing of a meal.

Cytokines profile and its correlation with endothelial damage and oxidative stress in patients with type 1 diabetes mellitus and nephropathy.

PubMed

Pestana, Rodrigo M C; Domingueti, Caroline P; Duarte, Rita C F; Fóscolo, Rodrigo B; Reis, Janice S; Rodrigues, Ana Maria S; Martins, Laís B; Sousa, Lirlândia P; Lage, Daniela P; Ferreira, Cláudia N; Ferreira, Adaliene V M; Fernandes, Ana P; Gomes, Karina B

2016-08-01

The aim of the present study was to investigate the association between the presence of albuminuria and cytokines profile with biomarkers of endothelial damage and oxidative stress in patients with type 1 diabetes mellitus (DM1). The sample was composed by 35 healthy individuals, 63 DM1 patients with normoalbuminuria (<30 mg of albumin/g of creatinine) and 62 DM1 patients with micro- and macroalbuminuria (≥30 mg of albumin/g of creatinine). Plasma and urinary cytokines (TNF-α, IL-6 and IL-10) and thrombomodulin levels were determined by ELISA. Oxidative status was evaluated using the TBARS and MTT assays. Diabetic patients were characterized by elevated levels of urinary cytokines TNF-α, IL-6 and IL-10. Those with macroalbuminuria presented significantly higher TNF-α and IL-10 urinary levels when compared to other groups. Urinary and plasmatic levels of TNF-α were positively correlated with plasma levels of cystatin C, creatinine, urea and albuminuria, while they were negatively correlated with estimated glomerular filtration rate. Urinary IL-10 levels proved positive correlation with fasting glucose, HbA1c, thrombomodulin and TBARS, while IL-6 plasma levels were positively correlated with HbA1c and albuminuria. Only urinary TNF-α levels were associated with the presence and severity of macroalbuminuria, after logistic regression analysis. This finding suggests that measurement of urinary TNF-α level may be helpful to evaluate progression to nephropathy in DM1 patients.

Stability of urea in solution and pharmaceutical preparations.

PubMed

Panyachariwat, Nattakan; Steckel, Hartwig

2014-01-01

The stability of urea in solution and pharmaceutical preparations was analyzed as a function of temperature (25°-60°C), pH (3.11-9.67), and initial urea concentration (2.5%-20%). This study was undertaken to (i) obtain more extensive, quantitative information relative to the degradation of urea in both aqueous and non-aqueous solutions and in pharmaceutical preparations, and (ii) test the effects of initial urea concentration, pH, buffer, and temperature values on urea degradation. The stability analysis shows that urea is more stable at the pH range of 4-8 and the stability of urea decreases by increase in temperature for all pH values. Within the experimental range of temperature and initial urea concentration values, the lowest urea degradation was found with lactate buffer pH 6.0. The urea decomposition rate in solution and pharmaceutical preparations shows the dependence of the initial urea concentrations. At higher initial urea concentrations, the rate of degradation is a decreasing function with time. This suggests that the reverse reaction is a factor in the degradation of concentrated urea solution. For non-aqueous solvents, isopropanol showed the best effort in retarding the decomposition of urea. Since the losses in urea is directly influenced by its stability at a given temperature and pH, the stability analysis of urea by the proposed model can be used to prevent the loss and optimize the operating condition for urea-containing pharmaceutical preparations.

Protective effects of the dietary supplementation of turmeric (Curcuma longa L.) on sodium arsenite-induced biochemical perturbation in mice.

PubMed

Karim, Md Rezaul; Haque, Abedul; Islam, Khairul; Ali, Nurshad; Salam, Kazi Abdus; Saud, Zahangir Alam; Hossain, Ekhtear; Fajol, Abul; Akhand, Anwarul Azim; Himeno, Seiichiro; Hossain, Khaled

2010-12-01

The present study was undertaken to evaluate the protective effect of turmeric powder on arsenic toxicity through mice model. Swiss albino male mice were divided into four groups. The first group was used as control, while groups 2, 3, and 4 were treated with turmeric powder (T, 50 mg/kg body weight/day), sodium arsenite (Sa, 10 mg/kg body weight/day) and turmeric plus Sa (T+Sa), respectively. Results showed that oral administration of Sa reduced the weight gain of the mice compared to the control group and food supplementation of turmeric prevented the reduction of weight gain. Turmeric abrogated the Sa-induced elevation of serum urea, glucose, triglyceride (TG) level and alanine aminotransferase (ALT) activity except the activity of alkaline phosphatase (ALP). Turmeric also prevented the Sa-induced perturbation of serum butyryl cholinesterase activity (BChE). Therefore, ameliorating effect of turmeric on Sa-treated mice suggested the future application of turmeric to reduce or to prevent arsenic toxicity in human.

Relative efficacy of carbenicillin indanyl sodium and of trimethoprim/sulfamethoxazole in urinary-tract infections.

PubMed

Seneca, H

1979-05-01

In a 10-day study, carbenicillin indanyl sodium cured urinary-tract infections in 22 of 30 patients (ages, 24-91). In 3 of the remaining patients the treatment was a failure; in 3 others the drug had to be discontinued because of diarrhea and vomiting; and in 2 instances it induced overgrowth of Candida albicans in the urine. Carbenicillin was lethal to Pseudomonas aeruginosa in all 9 cases, to Proteus mirabilis in all 6 cases, and to enterococcus in all 3 cases. A trimethoprim/sulfamethoxazole combination cured urinary-tract infections in 18 of 30 other patients (ages, 28-91), but failed in 3. In 3 patients it gave rise to a skin rash; in 2 to elevation of blood urea nitrogen and creatinine levels; in 1 to neutropenia; and in 1 to overgrowth of Candida albicans in the urine. Reinfection occurred in 2 patients. Carbenicillin indanyl sodium was more effective than the sulfonamide/trimethoprim combination.

Synthesis, biological evaluation and molecular docking of N-phenyl thiosemicarbazones as urease inhibitors.

PubMed

Hameed, Abdul; Khan, Khalid Mohammed; Zehra, Syeda Tazeen; Ahmed, Ramasa; Shafiq, Zahid; Bakht, Syeda Mahwish; Yaqub, Muhammad; Hussain, Mazhar; de la Vega de León, Antonio; Furtmann, Norbert; Bajorath, Jürgen; Shad, Hazoor Ahmad; Tahir, Muhammad Nawaz; Iqbal, Jamshed

2015-08-01

Urease is an important enzyme which breaks urea into ammonia and carbon dioxide during metabolic processes. However, an elevated activity of urease causes various complications of clinical importance. The inhibition of urease activity with small molecules as inhibitors is an effective strategy for therapeutic intervention. Herein, we have synthesized a series of 19 benzofurane linked N-phenyl semithiocarbazones (3a-3s). All the compounds were screened for enzyme inhibitor activity against Jack bean urease. The synthesized N-phenyl thiosemicarbazones had varying activity levels with IC50 values between 0.077 ± 0.001 and 24.04 ± 0.14 μM compared to standard inhibitor, thiourea (IC50 = 21 ± 0.11 μM). The activities of these compounds may be due to their close resemblance of thiourea. A docking study with Jack bean urease (PDB ID: 4H9M) revealed possible binding modes of N-phenyl thiosemicarbazones. Copyright © 2015 Elsevier Inc. All rights reserved.

Levels of lactic acid, normal level & its relation to food, glucose, cholesterol, raised blood urea and phenformin therapy.

PubMed

Patel, J C; Sawant, M S; Amin, B M

2000-01-01

1. The level of lactic acid was found to be 25 mg percent in 95 percent of 186 normal Indians. There was no difference due to sex and age. 2. Level of lactic acid was estimated in blood of normal persons and diabetics Type II patients to observe the effects of food and glucose. There was no change except the level of lactic acid was in higher but in normal range. 3. Hyperglycemia of over 300 mg raised the blood lactic acid in 25 percent of patients. 4. Lactic acid was not affected by hypercholesteremia but was raised in 60 percent of cases with raised blood urea. 5. Lactic acid was found to remain within normal limits in 48 type II diabetics treated with phenformin dose varying from 50 mg to 225 mg per day. The duration of treatment varied from one year to seven years.

Blood Test: Basic Metabolic Panel (BMP)

MedlinePlus

... the body's fluid levels and its acid-base balance. Normal levels of these electrolytes help keep cells in the body working as they should. Blood urea nitrogen (BUN) and creatinine , which are waste products filtered ...

Blood Test: Comprehensive Metabolic Panel (CMP)

MedlinePlus

... the body's fluid levels and its acid-base balance. Normal levels of these electrolytes help keep cells in the body working as they should. Blood urea nitrogen (BUN) and creatinine , which are waste products filtered ...

Passion fruit hulls particleboard: the effect of urea formaldehyde level on physical and mechanical properties

NASA Astrophysics Data System (ADS)

Iswanto, A. H.; Sucipto, T.; Adlina, E.; Prabuningrum, D. S.

2018-02-01

The purpose of this research was to explore the suitability of Passion Fruit Hulls (PFH) as a raw material particleboard with variants of urea formaldehyde adhesive content (UF). In this research, PFH particles filtered by sieve in size of 10 mesh to throw dust particles. Furthermore, the particles dried until reaches of 5% moisture content. Levels of UF adhesive was using comprise of 10%, 12% and 14%. Hot pressing conducted at 120°C temperature for 10 minutes at a pressure of 30 kg/cm2. The results showed that in moisture content for 10% adhesive level, almost all the parameters such as thickness swelling, modulus of elasticity (MOE) and modulus of rupture (MOR) that produced did not fulfiled the standard. The 14% adhesive level produced of the best of PFH particleboard.

Impairment of liver synthetic function and the production of plasma proteins in primary breast cancer patients on doxorubicincyclophosphamide (AC) protocol.

PubMed

Saleem, Zikria; Ahmad, Mobasher; Hashmi, Furqan Khurshid; Saeed, Hamid; Aziz, Muhammad Tahir

2016-09-01

Doxorubicin and Cyclophosphamide (AC protocol) combination is usually considered as a first line therapy in newly diagnosed breast cancer patients. Thus, a retrospective observational study was conducted to monitor the effect of AC protocol on liver synthetic functions and production of plasma proteins in breast cancer patients, reporting to specialized cancer care hospital of Lahore, Pakistan. A total of 75 patients (n=75) on AC protocol with breast cancer were observed in this study. The patient data including age, gender, body surface area, dosage, disease status and laboratory biochemical values were recorded by reviewing historical treatment records. Pre-treatment values were taken as baseline values for albumin, globulin, blood urea nitrogen (BUN), albumin/globulin (A/G) ratio and total proteins. The baseline values were compared after each cycle of by applying ANOVA using statistical tool SPSS® version 21. The plasma levels of blood urea nitrogen (BUN), total protein and globulin dropped significantly (p<0.05) in patients of all age groups. However, the albumin levels were not significantly changed (p>0.05). The A/G ratio level increased (p<0.05) as a result of reduction in globulin levels. Significant changes in plasma protein levels were observed in the elderly patients (50 to 65 years) than patients between 20 to 50 years of age. AC protocol impairs liver synthetic functions as observed by decreased blood urea nitrogen (BUN) and plasma protein levels.

Contribution of citrulline to the formation of ethyl carbamate during Chinese rice wine production.

PubMed

Wang, Peihong; Sun, Junyong; Li, Xiaomin; Wu, Dianhui; Li, Tong; Lu, Jian; Chen, Jian; Xie, Guangfa

2014-04-01

Ethyl carbamate is a well-known carcinogen and widely occurs in Chinese rice wine. To provide more clues to minimise ethyl carbamate accumulation, the levels of possible precursors of ethyl carbamate in Chinese rice wine were investigated by HPLC. Studies of the possible precursors of ethyl carbamate in Chinese raw rice wine with various additives and treatments indicated that significant amounts of urea can account for ethyl carbamate formation. It was also recognised that citrulline is another important precursor that significantly affects ethyl carbamate production during the boiling procedure used in the Chinese rice wine manufacturing process. Besides urea and citrulline, arginine was also found to be an indirect ethyl carbamate precursor due to its ability to form urea and citrulline by microorganism metabolism.

Expanded metabolic versatility of ubiquitous nitrite-oxidizing bacteria from the genus Nitrospira.

PubMed

Koch, Hanna; Lücker, Sebastian; Albertsen, Mads; Kitzinger, Katharina; Herbold, Craig; Spieck, Eva; Nielsen, Per Halkjaer; Wagner, Michael; Daims, Holger

2015-09-08

Nitrospira are a diverse group of nitrite-oxidizing bacteria and among the environmentally most widespread nitrifiers. However, they remain scarcely studied and mostly uncultured. Based on genomic and experimental data from Nitrospira moscoviensis representing the ubiquitous Nitrospira lineage II, we identified ecophysiological traits that contribute to the ecological success of Nitrospira. Unexpectedly, N. moscoviensis possesses genes coding for a urease and cleaves urea to ammonia and CO2. Ureolysis was not observed yet in nitrite oxidizers and enables N. moscoviensis to supply ammonia oxidizers lacking urease with ammonia from urea, which is fully nitrified by this consortium through reciprocal feeding. The presence of highly similar urease genes in Nitrospira lenta from activated sludge, in metagenomes from soils and freshwater habitats, and of other ureases in marine nitrite oxidizers, suggests a wide distribution of this extended interaction between ammonia and nitrite oxidizers, which enables nitrite-oxidizing bacteria to indirectly use urea as a source of energy. A soluble formate dehydrogenase lends additional ecophysiological flexibility and allows N. moscoviensis to use formate, with or without concomitant nitrite oxidation, using oxygen, nitrate, or both compounds as terminal electron acceptors. Compared with Nitrospira defluvii from lineage I, N. moscoviensis shares the Nitrospira core metabolism but shows substantial genomic dissimilarity including genes for adaptations to elevated oxygen concentrations. Reciprocal feeding and metabolic versatility, including the participation in different nitrogen cycling processes, likely are key factors for the niche partitioning, the ubiquity, and the high diversity of Nitrospira in natural and engineered ecosystems.

Alterations in malondialdehyde levels and laboratory parameters among methamphetamine abusers.

PubMed

Suriyaprom, Kanjana; Tanateerabunjong, Rossukon; Tungtrongchitr, Anchalee; Tungtrongchitr, Rungsunn

2011-12-01

To determine the concentrations of malondialdehyde, biochemical, and hematological parameters among methamphetamine abusers compared with a healthy control group and to evaluate the association between malondialdehyde and biochemical-hematological parameters. The concentrations of malondialdehyde, lipids, liver enzymes, albumin, blood urea nitrogen, creatinine, and hematological measurements were determined in 60 methamphetamine abusers and 60 controls. Significantly higher levels of malondialdehyde were found in the methamphetamine abusers than the controls [2.45 (2.12-2.81) vs. 1.41 (1.15-2.08)]. The levels ofalanine aminotransferase and alkaline phosphatase and white blood cell and platelet counts of the methamphetamine abusers were significantly elevated (p-value < 0.05) compared with the controls. Meanwhile, the levels of hemoglobin, hematocrit, albumin and body mass index were significantly lower among the methamphetamine-abusing group than the control group (p-value < 0.05). It was found that higher numbers of methamphetamine tablets per day were associated with higher malondialdehyde concentrations in methamphetamine abusers, and that malondialdehyde concentration inversely correlated with albumin level (r = -0.458, p-value < 0.05). Stepwise multiple regression analysis revealed that number of methamphetamine tablets per day, white blood cell count and albumin level were independent predictors of malondialdehyde level (p-value < 0.05). Methamphetamine abuse is related to increased lipid peroxidation, changes in inflammatory marker level, increase in liver enzymes, and decrease in hemoglobin and hematocrit concentrations. These effects may be early signs of the development of diseases associated with methamphetamine abuse.

The physiology of the Tambaqui (Colossoma macropomum) at pH 8.0.

PubMed

Wood, Chris M; Gonzalez, R J; Ferreira, Márcio Soares; Braz-Mota, Susana; Val, Adalberto Luis

2018-05-01

The Tambaqui is a model neotropical teleost which is of great economic and cultural importance in artisanal fisheries and commercial aquaculture. It thrives in ion-poor, often acidic Amazonian waters and exhibits excellent regulation of physiology down to water pH 4.0. Curiously, however, it is reported to perform poorly in aquaculture at pH 8.0, an only slightly alkaline pH which would be benign for most freshwater fish. In initial experiments with Tambaqui of intermediate size (30-50 g), we found that ammonia excretion rate was unchanged at pH 4, 5, 6, and 7, but elevated after 20-24 h at pH 8, exactly opposite the pattern seen in most teleosts. Subsequent experiments with large Tambaqui (150-300 g) demonstrated that only ammonia, and not urea excretion was increased at pH 8.0, and that the elevation was proportional to a general increase in MO 2 . There was an accompanying elevation in net acidic equivalent excretion and/or basic equivalent uptake which occurred mainly at the gills. Net Na + balance was little affected while Cl - balance became negative, implicating a disturbance of Cl - versus base exchange rather than Na + versus acid exchange. Arterial blood pH increased by 0.2 units at pH 8.0, reflecting combined metabolic and respiratory alkaloses. Most parameters recovered to control levels by 18-24 h after return to pH 6.0. With respect to large Tambaqui, we conclude that a physiology adapted to acidic pH performs inappropriately at moderately alkaline pH. In small Tambaqui (4-15 g), the responses were very different, with an initial inhibition of ammonia excretion rate at pH 8.0 followed by a subsequent restoration of control levels. Elevated ammonia excretion rate occurred only after return to pH 6.0. Furthermore, MO 2 , plasma cortisol, and branchial vH + ATPase activities all declined during pH 8.0 exposure in small Tambaqui, in contrast to the responses in larger fish. Overall, small Tambaqui appear to cope better at pH 8.0, a difference that may correlate with their natural history in the wild.

Physiological and molecular ontogeny of branchial and extra-branchial urea excretion in posthatch rainbow trout (Oncorhynchus mykiss).

PubMed

Zimmer, Alex M; Wood, Chris M

2016-02-01

All teleost fish produce ammonia as a metabolic waste product. In embryos, ammonia excretion is limited by the chorion, and fish must detoxify ammonia by synthesizing urea via the ornithine urea cycle (OUC). Although urea is produced by embryos and larvae, urea excretion (J(urea)) is typically low until yolk sac absorption, increasing thereafter. The aim of this study was to determine the physiological and molecular characteristics of J(urea) by posthatch rainbow trout (Oncorhynchus mykiss). Following hatch, whole body urea concentration decreased over time, while J(urea) increased following yolk sac absorption. From 12 to 40 days posthatch (dph), extra-branchial routes of excretion accounted for the majority of J(urea), while the gills became the dominant site for J(urea) only after 55 dph. This represents the most delayed branchial ontogeny of any process studied to date. Urea transporter (UT) gene expression in the gills and skin increased over development, consistent with increases in branchial and extra-branchial J(urea). Following exposure to 25 mmol/l urea, the accumulation and subsequent elimination of exogenous urea was much greater at 55 dph than 12 dph, consistent with increased UT expression. Notably, UT gene expression in the gills of 55 dph larvae increased in response to high urea. In summary, there is a clear increase in urea transport capacity over posthatch development, despite a decrease in OUC activity. Copyright © 2016 the American Physiological Society.

Urea transporter knockout mice and their renal phenotypes.

PubMed

Fenton, Robert A; Yang, Baoxue

2014-01-01

Urea transporter gene knockout mice have been created for the study of the urine-concentrating mechanism. The major findings in studies of the renal phenotype of these mice are as follows: (1) Urea accumulation in the inner medullary interstitium is dependent on intrarenal urea recycling mediated by urea transporters; (2) urea transporters are essential for preventing urea-induced osmotic diuresis and thus for water conservation; (3) NaCl concentration in the inner medullary interstitium is not significantly affected by the absence of IMCD, descending limb of Henle and descending vasa recta urea transporters. Studies in urea transporter knockout mouse models have highlighted the essential role of urea for producing maximally concentrated urine.

Effect of chromium picolinate on histopathological alterations in STZ and neonatal STZ diabetic rats.

PubMed

Shinde, Urmila A; Goyal, R K

2003-01-01

Earlier studies from our laboratory have indicated insulin sensitizing action of chromium picolinate as the mechanism of its anti-diabetic activity in experimental models of type I and type II diabetes. In the present investigation, we have evaluated the effects of chronic administration of chromium picolinate on the functional and histological alterations of streptozotocin (STZ)-induced diabetes in rats. Type I diabetes was induced by intravenous injection of STZ (40 mg/kg) in adult rats, whereas, type II diabetes was induced by intraperitoneal injection of STZ (90 mg/kg) in 2-day old rat pups which in adulthood develop abnormalities resembling type II diabetes. Chromium picolinate was administered at 8 microg/ml in drinking water for 6 weeks and was found to improve glucose tolerance and increase insulin sensitivity of STZ-diabetic rats. This treatment decrease elevated serum creatinine and urea levels as well as elevated serum levels of hepatic enzymes of both groups of diabetic rats. Histopathological studies of kidney and liver show decrease in the intensity and incidence of vacuolations, cellular infiltration and hypertrophy of STZ and nSTZ (neonatal STZ) diabetic rats. Chronic treatment with chromium picolinate however, did not alter the normal function or morphology of control rats. Chronic chromium picolinate at the therapeutic doses that improved glucose tolerance, was observed to have no hepatotoxic or nephrotoxic potential. It was rather found to improve renal and hepatic function and to reduce abnormalities associated with STZ-diabetes. Chromium picolinate could play an important role in the long term management of diabetes mellitus.

Improving ammonium and nitrate release from urea using clinoptilolite zeolite and compost produced from agricultural wastes.

PubMed

Omar, Latifah; Ahmed, Osumanu Haruna; Ab Majid, Nik Muhamad

2015-01-01

Improper use of urea may cause environmental pollution through NH3 volatilization and NO3 (-) leaching from urea. Clinoptilolite zeolite and compost could be used to control N loss from urea by controlling NH4 (+) and NO3 (-) release from urea. Soil incubation and leaching experiments were conducted to determine the effects of clinoptilolite zeolite and compost on controlling NH4 (+) and NO3 (-) losses from urea. Bekenu Series soil (Typic Paleudults) was incubated for 30, 60, and 90 days. A soil leaching experiment was conducted for 30 days. Urea amended with clinoptilolite zeolite and compost significantly reduced NH4 (+) and NO3 (-) release from urea (soil incubation study) compared with urea alone, thus reducing leaching of these ions. Ammonium and NO3 (-) leaching losses during the 30 days of the leaching experiment were highest in urea alone compared with urea with clinoptilolite zeolite and compost treatments. At 30 days of the leaching experiment, NH4 (+) retention in soil with urea amended with clinoptilolite zeolite and compost was better than that with urea alone. These observations were because of the high pH, CEC, and other chemical properties of clinoptilolite zeolite and compost. Urea can be amended with clinoptilolite zeolite and compost to improve NH4 (+) and NO3 (-) release from urea.

Kt/Vurea and Nonurea Small Solute Levels in the Hemodialysis Study

PubMed Central

Sirich, Tammy L.; Fong, Kara D.; Plummer, Natalie S.; Shafi, Tariq; Hwang, Seungyoung; Banerjee, Tanushree; Zhu, Yunnuo; Powe, Neil R.; Hai, Xin; Hostetter, Thomas H.

2016-01-01

The Hemodialysis (HEMO) Study showed that high-dose hemodialysis providing a single-pool Kt/Vurea of 1.71 provided no benefit over a standard treatment providing a single-pool Kt/Vurea of 1.32. Here, we assessed whether the high-dose treatment used lowered plasma levels of small uremic solutes other than urea. Measurements made ≥3 months after randomization in 1281 patients in the HEMO Study showed a range in the effect of high-dose treatment compared with that of standard treatment: from no reduction in the level of p-cresol sulfate or asymmetric dimethylarginine to significant reductions in the levels of trimethylamine oxide (−9%; 95% confidence interval [95% CI], −2% to −15%), indoxyl sulfate (−11%; 95% CI, −6% to −15%), and methylguanidine (−22%; 95% CI, −18% to −27%). Levels of three other small solutes also decreased slightly; the level of urea decreased 9%. All-cause mortality did not significantly relate to the level of any of the solutes measured. Modeling indicated that the intermittency of treatment along with the presence of nondialytic clearance and/or increased solute production accounted for the limited reduction in solute levels with the higher Kt/Vurea. In conclusion, failure to achieve greater reductions in solute levels may explain the failure of high Kt/Vurea treatment to improve outcomes in the HEMO Study. Furthermore, levels of the nonurea solutes varied widely among patients in the HEMO Study, and achieved Kt/Vurea accounted for very little of this variation. These results further suggest that an index only on the basis of urea does not provide a sufficient measure of dialysis adequacy. PMID:27026365

Recent analytical approaches to detect exhaled breath ammonia with special reference to renal patients.

PubMed

Krishnan, Sanduru Thamarai; Devadhasan, Jasmine Pramila; Kim, Sanghyo

2017-01-01

The ammonia odor from the exhaled breath of renal patients is associated with high levels of blood urea nitrogen. Typically, in the liver, ammonia and ammonium ions are converted into urea through the urea cycle. In the case of renal dysfunction, urea is unable to be removed and that causes a buildup of excessive ammonia. As small molecules, ammonia and ammonium ions can be forced into the blood-lung barrier and occur in exhaled breath. Therefore, people with renal failure have an ammonia (fishy) odor in their exhaled breath. Thus, exhaled breath ammonia can be a potential biomarker for monitoring renal diseases during hemodialyis. In this review, we have summarized the source of ammonia in the breath of end-stage renal disease patient, cause of renal disorders, exhaled breath condensate, and breath sampling. Further, various biosensor approaches to detect exhaled ammonia from renal patients and other ammonia systems are also discussed. We conclude with future perspectives, namely colorimetric-based real-time breathing diagnosis of renal failure, which might be useful for prospective studies.

Renal and biochemical changes produced in broilers by high-protein, high-calcium, urea-containing, and vitamin-A-deficient diets.

PubMed

Chandra, M; Singh, B; Soni, G L; Ahuja, S P

1984-01-01

Three hundred 18-day-old male chicks (Arbor Acre) were divided into five groups of 60 each and given high-protein (42.28%), high-calcium (3.37%), urea-containing (5%), vitamin-A-deficient, or control diets to study the effect of nutritional imbalances on the development of nephritis and related biochemical changes over 15 weeks. The first four diets increased the levels of glutamate oxaloacetate transaminase, glutamate pyruvate transaminase, uric acid, and nonprotein nitrogen in serum. Blood urea was increased by only the urea diet. Hypoglycemia and a decrease in hepatic glucose-6-phosphatase were also observed in chicks fed the first four diets. The vitamin-A-deficient diet resulted in a depletion of vitamin A in the liver and kidneys. These changes were directly correlated with the prolonged feeding of experimental diets and also with the severity of nephritis and degenerative changes in various organs. It was concluded that increasing the intake of nitrogen or calcium in order to increase production may in fact have the opposite effect, leading to degenerative changes in various tissues and to nephritis.

Performance of composite boards from long strand oil palm trunk bonded by isocyanate and urea formaldehyde adhesives

NASA Astrophysics Data System (ADS)

Hermanto, Indra; Massijaya, M. Y.

2018-03-01

In this research, the obtained long strand were produced from the outer part of oil palm trunk and then hot-prepressed. The three-ply composite boards were made from hot-prepressed long strand and use bonded by isocyanate and urea formaldehyde adhesives with a glue spread variation of 150 g/m2, 225 g/m2, and 300 g/m2. The board target density was 0.65 g/cm3, face and back layers orientation is the same and the core layer was perpendicular to the face and back layers. The research results showed that : (1) composite boards bonded by isocyanate performed better physical and mechanical properties compared to those of bonded by urea formaldehyde, (2) utilization of higher glue spread level would improve the physical and mechanical properties of the composite board. (3) composite boards bonded by isocyanate and urea formaldehyde adhesives at glue spread of 225 g/m2, 300 g/m2, respectively were enough to fulfill the JIS A 5908 (2003) standard.

Isotopic studies of urea metabolism in rabbits

PubMed Central

Regoeczi, E.; Irons, L.; Koj, A.; McFarlane, A. S.

1965-01-01

1. The half-life of [15N]urea was found to be significantly longer than that of [14C]urea injected at the same time, the differences being due to endogenous catabolism of urea, which is accompanied by little or no reutilization of 14C but is approx. 20% for 15N. [15N]Urea therefore appears to be valueless as an indicator of nitrogen metabolism unless the extents of endogenous catabolism of urea and of fractional reutilization of 15N can be separately estimated. 2. Though measurements of the radioactivity of expired 14CO2 confirmed the existence of considerable urea catabolism these could not be used for quantitative assessments. 3. Alternative graphical methods based on [14C]urea specific activities in plasma and urine samples were used to calculate the fraction of urea production that is excreted. Values by the two methods were in good agreement and showed that some animals excrete less than half the urea that they produce. 4. Specific activity differences between simultaneous samples of urinary and plasma urea reflect the presence of a pool of urea in the kidney that is not in equilibrium with the body urea pool. Calculations indicate the presence of urea in the kidney that in some cases may represent as much as 15% of the body pool, and in two animals in which post-mortem renal analyses were performed the masses of urea found agreed closely with the calculated values. 5. A model for urea metabolism is proposed that includes this pool in the excretory pathway. The related theory is shown to be adequate to explain the shape of the specific activity curves of urinary urea from the time of injection and the constant delay of the specific activity of urinary urea, relative to that of plasma urea, that is observed after a short preliminary equilibration period. 6. The body urea pool was calculated from the activity retained at 1·5hr. by excluding renal activity and the corrected specific activity of plasma urea at the same time. The urea pool was calculated to be distributed at the plasma concentration in a substantially smaller water volume than that found by injecting tritiated water in five animals. Reasons for this are discussed. 7. Urea synthesis rates calculated from the pool values are in close agreement with rates calculated from the mass of urea recovered in the urine and the fraction of newly synthesized urea that is excreted. PMID:14340103

Analysis of Consequences of Birth Asphyxia in Infants: A Regional Study in Southern Punjab, Pakistan.

PubMed

Samad, Noreen; Farooq, Samia; Hafeez, Kinza; Maryam, Mukharma; Rafi, Muhammad Aftab

2016-12-01

To evaluate the biochemical consequences and platelet counts of birth asphyxia in neonates. Cohort study. Department of Child Health, Nishter Medical College and Hospital, Multan, from September to November 2015. The data of 50 (50%) asphyxiated neonates and 50 (50%) non-asphyxiated neonates, with age range less than 1 month, was collected from Children Ward of Nishtar Hospital, Multan, Pakistan. Data on platelet count in blood, kidney function tests (creatinine, urea), liver function tests (bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST)) and cardiac enzyme test (lactate dehydrogenase (LDH)) were analysed by paired sample t-test by SPSS software. Sociodemographic data of those neonate's mothers was also collected. In asphyxiated neonates LDH, ALT, AST, creatinine, bilirubin, urea levels were higher than healthy infants, while the platelet count was smaller in asphyxiated neonates than healthy infants. There was a higher rate of alteration in platelet count, levels of LDH, AST, ALT, urea creatinine and bilirubin in asphyxiated infants. These alterations may be correlated with damage of vital organ of asphyxiated neonates.

Biochemical differences in ethnic groups in Durango, Mexico.

PubMed

Lares-Asseff, Ismael; Lujín-García, Azalia; Sosa-Macías, Martha; Lazalde-Ramos, Blanca; Loera-Castañeda, Veronica; Galaviz-Hernández, Carlos; Villanueva-Fierro, Ignacio

2012-01-01

The aim of this study was to assess biochemical differences between Tepehuano indigenous people, and Mennonite and Mestizo populations of Durango, Mexico. Our study involved 334 volunteers aged 15 to 80 years; 132 Mennonite and 130 Mestizo individuals from Nuevo Ideal Municipality and 72 Tepehuano indigenous people from Mezquital Durango were evaluated. A clinical history and fast determination of aspartate aminotransferase (AST), alanine aminotransferase (ALT), uric acid, urea and creatinine were performed on each studied case. Statistically significant differences between the three studied groups were found for age, weight and height (P < .05), with higher values observed in men. The highest plasma urea levels were found in Mennonite compared to Mestizo people, followed by the Tepehuano indigenous. Higher biochemical parameters were found in men (vs women) in the studied groups. The percentage of individuals with abnormal levels for AST, ALT and uric acid were higher in Tepehuano indigenous people than in Mestizo, whereas the urea and creatinine percentages were higher in Mestizo people. The differences found on biochemical tests, could be explained by differences in lifestyle such as diet and sanitary habits.

Electrochemical fabrication of nanoporous copper films in choline chloride-urea deep eutectic solvent.

PubMed

Zhang, Q B; Abbott, Andrew P; Yang, C

2015-06-14

Nanoporous copper films were fabricated by a facile electrochemical alloying/dealloying process without the need of a template. A deep eutectic solvent made from choline chloride (ChCl) and urea was used with zinc oxide as the metal salt. Cyclic voltammetry was used to characterise the electrochemical reduction of zinc and follow Cu-Zn alloy formation on the copper substrate at elevated temperatures from 353 to 393 K. The alloy formation was confirmed by X-ray diffraction spectra. 3D, open and bicontinuous nanoporous copper films were obtained by in situ electrochemically etching (dealloying) of the zinc component in the Cu-Zn surface alloys at an appropriate potential (-0.4 V vs. Ag). This dealloying process was found to be highly temperature dependent and surface diffusion controlled, which involved the self-assembly of copper atoms at the alloy/electrolyte interface. Additionally, the effects of the deposition parameters, including deposition temperature, current density as well as total charge density on resulting the microstructure were investigated by scanning electron microscopy, and atomic force microscope.

Estimate of production of gaseous nitrogen in the human body based on (15)N analysis of breath N2 after administration of [(15)N2]urea.

PubMed

Junghans, Peter

2013-01-01

After oral administration of [(15)N2]urea (1.5 mmol, 95 atom% (15)N), we found that breath N2 was significantly (15)N-labelled. The result suggests that molecular nitrogen in breath must be partly produced endogenously. Based on a metabolic model, the endogenous N2 production was estimated to be 0.40±0.25 mmol kg(-1) d(-1) or 2.9±1.8 % of the total (urinary and faecal) N excretion in fasted healthy subjects (n=4). In patients infected with Helicobacter pylori (n=5), the endogenous N2 production was increased to 1.24±0.59 mmol kg(-1) d(-1) or 9.0±4.3 % of the total N excretion compared to the healthy controls (p<0.05). We conclude that N balance and gas exchange measurements may be affected by endogenously produced nitrogen, especially in metabolic situations with elevated nitrosation, for instance in oxidative and nitrosative stress-related diseases such as H. pylori infections.

Deposits from Creams Containing 20% (w/w) Urea and Suppression of Crystallization (Part 2): Novel Analytical Methods of Urea Accumulated in the Stratum Corneum by Tape stripping and Colorimetry.

PubMed

Goto, Norio; Morita, Yutaka; Terada, Katsuhide

2016-01-01

The transfer of urea from a urea formulation to the stratum corneum varies with the formulation base and form, and impacts the formulation's therapeutic effect. Consequently, determining the amount of urea transferred is essential for developing efficient formulations. This study assessed a simple method for measuring the amount of urea accumulated in the stratum corneum. Conventional methods rely on labeling urea used in the formulation with radiocarbon ((14)C) or other radioactive isotopes (RIs), retrieving the transferred urea from the stratum corneum by tape stripping, then quantitating the urea. The handling and use of RIs, however, is subject to legal regulation and can only be performed in sanctioned facilities, so methods employing RIs are neither simple nor convenient. We therefore developed a non-radiolabel method "tape stripping-colorimetry (T-C)" that combines tape stripping with colorimetry (urease-glutamate dehydrogenase (GLDH)) for the quantitative measurement of urea. Urea in the stratum corneum is collected by tape stripping and measured using urease-GLDH, which is commonly used to measure urea nitrogen in blood tests. The results indicate that accurate urea measurement by the T-C method requires the application of 1400 mg (on hairless rats) of a 20% urea solution on a 50 cm(2) (5×10 cm) area. Further, we determined the amount of urea accumulated in the stratum corneum using formulations with different urea concentrations, and the time course of urea accumulation from formulations differing in the rate of urea crystallization. We demonstrate that the T-C method is simple and convenient, with no need for (14)C or other RIs.

How Helicobacter pylori urease may affect external pH and influence growth and motility in the mucus environment: evidence from in-vitro studies.

PubMed

Sidebotham, Ramon L; Worku, Mulugeta L; Karim, Q Najma; Dhir, Nirmal K; Baron, J Hugh

2003-04-01

Survival of Helicobacter pylori is dependent upon urease in the cytoplasm and at the bacterial surface. We have sought to clarify how alkaline ammonium salts, released from urea by this enzyme, might alter mucus pH and so affect growth and motility of the bacterium in the gastric mucus environment. Experiments were conducted in vitro to determine how the growth and motility of H. pylori are affected by changes in external pH, and how the bacterium, by hydrolysing urea, alters the pH of the bicarbonate buffer that occurs at the gastric mucosal surface. These data were fitted into experimental models that describe how pH varies within the mucus layer in the acid-secreting stomach. H. pylori was motile between pH 5 and 8, with optimal motility at pH 5. It grew between pH 6 and 8, with optimal growth at pH 6. The bacterium had urease activity between pH 2.7 and 7.4, as evidenced by pH rises in bicarbonate-buffered solutions of urea. Changes in buffer pH were dependent upon initial pH and urea concentration, with the greatest rate of pH change occurring at pH 3. Modelling experiments utilizing these data indicated that (1) in the absence of urease, H. pylori growth and motility in the mucus layer would be restricted severely by low mucus pH in the acid-secreting stomach, and (2) urease will sometimes inhibit H. pylori growth and motility in the mucus layer by elevating the pH of the mucus environment above pH 8. Urease is essential to the growth and motility of H. pylori in the mucus layer in the acid-secreting stomach, but, paradoxically, sometimes it might suppress colonization by raising the mucus pH above 8. This latter effect may protect the bacteria from the adverse consequences of overpopulation.

Effect of dietary protein concentration and degradability on response to rumen-protected methionine in lactating dairy cows.

PubMed

Broderick, G A; Stevenson, M J; Patton, R A

2009-06-01

An incomplete 8 x 8 Latin square trial (4-wk periods; 12 wk total) using 32 multiparous and 16 primiparous Holstein cows was conducted to assess the production response to crude protein (CP), digestible rumen-undegraded protein (RUP), and rumen-protected Met (RPM; fed as Mepron; Degussa Corp., Kennesaw, GA). Diets contained [dry matter (DM) basis] 21% alfalfa silage, 34% corn silage, 22 to 26% high-moisture corn, 10 to 14% soybean meal, 4% soyhulls, 2% added fat, 1.3% minerals and vitamins, and 27 to 28% neutral detergent fiber. Treatments were a 2 x 2 x 2 factorial arrangement of the following main effects: 15.8 or 17.1% dietary CP, with or without supplemental rumen-undegraded protein (RUP) from expeller soybean meal, and 0 or 9 g of RPM/d. None of the 2- or 3-way interactions was significant. Higher dietary CP increased DM intake 1.1 kg/d and yield of milk 1.7 kg/d, 3.5% fat-corrected milk (FCM) 2.2 kg/d, fat 0.10 kg/d, and true protein 0.05 kg/d, and improved apparent N balance and DM and fiber digestibility. However, milk urea N and estimated urinary excretion of urea-N and total-N also increased, and apparent N efficiency (milk-N/N-intake) fell from 33 to 30% when cows consumed higher dietary CP. Positive effects of feeding more RUP were increased feed efficiency and milk fat content plus 1.8 kg/d greater FCM and 0.08 kg/d greater fat, but milk protein content was lower and milk urea N and urinary urea excretion were elevated. Supplementation with RPM increased DM intake 0.7 kg/d and FCM and fat yield by 1.4 and 0.06 kg/d, and tended to increase milk fat content and yield of milk and protein.

Urea metabolism in plants.

PubMed

Witte, Claus-Peter

2011-03-01

Urea is a plant metabolite derived either from root uptake or from catabolism of arginine by arginase. In agriculture, urea is intensively used as a nitrogen fertilizer. Urea nitrogen enters the plant either directly, or in the form of ammonium or nitrate after urea degradation by soil microbes. In recent years various molecular players of plant urea metabolism have been investigated: active and passive urea transporters, the nickel metalloenzyme urease catalyzing the hydrolysis of urea, and three urease accessory proteins involved in the complex activation of urease. The degradation of ureides derived from purine breakdown has long been discussed as a possible additional metabolic source for urea, but an enzymatic route for the complete hydrolysis of ureides without a urea intermediate has recently been described for Arabidopsis thaliana. This review focuses on the proteins involved in plant urea metabolism and the metabolic sources of urea but also addresses open questions regarding plant urea metabolism in a physiological and agricultural context. The contribution of plant urea uptake and metabolism to fertilizer urea usage in crop production is still not investigated although globally more than half of all nitrogen fertilizer is applied to crops in the form of urea. Nitrogen use efficiency in crop production is generally well below 50% resulting in economical losses and creating ecological problems like groundwater pollution and emission of nitric oxides that can damage the ozone layer and function as greenhouse gasses. Biotechnological approaches to improve fertilizer urea usage bear the potential to increase crop nitrogen use efficiency. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Urea-Aromatic Stacking and Concerted Urea Transport: Conserved Mechanisms in Urea Transporters Revealed by Molecular Dynamics.

PubMed

Padhi, Siladitya; Priyakumar, U Deva

2016-10-11

Urea transporters are membrane proteins that selectively allow urea molecules to pass through. It is not clear how these transporters allow rapid conduction of urea, a polar molecule, in spite of the presence of a hydrophobic constriction lined by aromatic rings. The current study elucidates the mechanism that is responsible for this rapid conduction by performing free energy calculations on the transporter dvUT with a cumulative sampling time of about 1.3 μs. A parallel arrangement of aromatic rings in the pore enables stacking of urea with these rings, which, in turn, lowers the energy barrier for urea transport. Such interaction of the rings with urea is proposed to be a conserved mechanism across all urea-conducting proteins. The free energy landscape for the permeation of multiple urea molecules reveals an interplay between interurea interaction and the solvation state of the urea molecules. This is for the first time that multiple molecule permeation through any small molecule transporter has been modeled.

A Fragment of the LG3 Peptide of Endorepellin Is Present in the Urine of Physically Active Mining Workers: A Potential Marker of Physical Activity

PubMed Central

Parker, Tony J.; Sampson, Dayle L.; Broszczak, Daniel; Chng, Yee L.; Carter, Shea L.; Leavesley, David I.; Parker, Anthony W.; Upton, Zee

2012-01-01

Biomarker analysis has been implemented in sports research in an attempt to monitor the effects of exertion and fatigue in athletes. This study proposed that while such biomarkers may be useful for monitoring injury risk in workers, proteomic approaches might also be utilised to identify novel exertion or injury markers. We found that urinary urea and cortisol levels were significantly elevated in mining workers following a 12 hour overnight shift. These levels failed to return to baseline over 24 h in the more active maintenance crew compared to truck drivers (operators) suggesting a lack of recovery between shifts. Use of a SELDI-TOF MS approach to detect novel exertion or injury markers revealed a spectral feature which was associated with workers in both work categories who were engaged in higher levels of physical activity. This feature was identified as the LG3 peptide, a C-terminal fragment of the anti-angiogenic/anti-tumourigenic protein endorepellin. This finding suggests that urinary LG3 peptide may be a biomarker of physical activity. It is also possible that the activity mediated release of LG3/endorepellin into the circulation may represent a biological mechanism for the known inverse association between physical activity and cancer risk/survival. PMID:22457785

A fragment of the LG3 peptide of endorepellin is present in the urine of physically active mining workers: a potential marker of physical activity.

PubMed

Parker, Tony J; Sampson, Dayle L; Broszczak, Daniel; Chng, Yee L; Carter, Shea L; Leavesley, David I; Parker, Anthony W; Upton, Zee

2012-01-01

Biomarker analysis has been implemented in sports research in an attempt to monitor the effects of exertion and fatigue in athletes. This study proposed that while such biomarkers may be useful for monitoring injury risk in workers, proteomic approaches might also be utilised to identify novel exertion or injury markers. We found that urinary urea and cortisol levels were significantly elevated in mining workers following a 12 hour overnight shift. These levels failed to return to baseline over 24 h in the more active maintenance crew compared to truck drivers (operators) suggesting a lack of recovery between shifts. Use of a SELDI-TOF MS approach to detect novel exertion or injury markers revealed a spectral feature which was associated with workers in both work categories who were engaged in higher levels of physical activity. This feature was identified as the LG3 peptide, a C-terminal fragment of the anti-angiogenic/anti-tumourigenic protein endorepellin. This finding suggests that urinary LG3 peptide may be a biomarker of physical activity. It is also possible that the activity mediated release of LG3/endorepellin into the circulation may represent a biological mechanism for the known inverse association between physical activity and cancer risk/survival.

Testicular dysfunction in experimental chronic renal insufficiency: a deficiency of nocturnal pineal N-acetyltransferase activity.

PubMed Central

Holmes, E. W.; Hojvat, S. A.; Kahn, S. E.; Bermes, E. W.

1989-01-01

Biochemical correlates of neuroendocrine/gonadal function and nocturnal levels of serotonin N-acetyltransferase (NAT) activity were determined in partially nephrectomized (PNx), male, Long Evans rats following a 5-week period of chronic renal insufficiency (CRI). PNx animals demonstrated two to four-fold elevations in urea nitrogen and three to four-fold reductions (P less than 0.02) in plasma total testosterone concentrations as compared to sham-operated controls. The pituitary LH contents of PNx rats were decreased to approximately 60% of the control value (P less than 0.05). There were no differences in plasma prolactin levels between the control and PNx groups either at mid-day or in the middle of the night. Nocturnal pineal NAT activity in PNx rats was markedly reduced to approximately 20% of the control value (P less than 0.001). Similar evidence of gonadal dysfunction (reduced plasma total testosterone and testes testosterone content) and a significant decrease in night-time levels of pineal NAT activity were also observed after 13 weeks of CRI in PNx rats of the Sprague-Dawley strain that were housed under a different photoperiod. These results suggest that pineal gland dysfunction is a feature of CRI in the PNx model. Such an abnormality might contribute to the pathogenesis of gonadal dysfunction in CRI. PMID:2765391

Amino acid metabolism during exercise in trained rats: the potential role of carnitine in the metabolic fate of branched-chain amino acids.

PubMed

Ji, L L; Miller, R H; Nagle, F J; Lardy, H A; Stratman, F W

1987-08-01

The influence of endurance training and an acute bout of exercise on plasma concentrations of free amino acids and the intermediates of branched-chain amino acid (BCAA) metabolism were investigated in the rat. Training did not affect the plasma amino acid levels in the resting state. Plasma concentrations of alanine (Ala), aspartic acid (Asp), asparagine (Asn), arginine (Arg), histidine (His), isoleucine (Ile), leucine (Leu), lysine (Lys), methionine (Met), phenylalanine (Phe), proline (Pro), serine (Ser), threonine (Thr), and valine (Val) were significantly lower, whereas glutamate (Glu), glycine (Gly), ornithine (Orn), tryptophan (Trp), tyrosine (Tyr), creatinine, urea, and ammonia levels were unchanged, after one hour of treadmill running in the trained rats. Plasma concentration of glutamine (Glu), the branched-chain keto acids (BCKA) and short-chain acyl carnitines were elevated with exercise. Ratios of plasma BCAA/BCKA were dramatically lowered by exercise in the trained rats. A decrease in plasma-free carnitine levels was also observed. These data suggest that amino acid metabolism is enhanced by exercise even in the trained state. BCAA may only be partially metabolized within muscle and some of their carbon skeletons are released into the circulation in forms of BCKA and short-chain acyl carnitines.

Determination of urea kinetics by isotope dilution with [13C]urea and gas chromatography-isotope ratio mass spectrometry (GC-IRMS) analysis.

PubMed

Kloppenburg, W D; Wolthers, B G; Stellaard, F; Elzinga, H; Tepper, T; de Jong, P E; Huisman, R M

1997-07-01

1. Stable urea isotopes can be used to study urea kinetics in humans. The use of stable urea isotopes for studying urea kinetic parameters in humans on a large scale is hampered by the high costs of the labelled material. We devised a urea dilution for measurement of the distribution volume, production rate and clearance of urea in healthy subjects and renal failure patients using the inexpensive single labelled [13C]urea isotope with subsequent analysis by headspace chromatography-isotope ratio MS (GC-IRMS) of the [13C]urea enrichment. 2. The method involves measurement of the molar percentage excess of [13C]urea in plasma samples taken over a 4 h period after an intravenous bolus injection of [13C]urea. During the sample processing procedure, the plasma samples together with calibration samples containing a known molar percentage excess of [13C]urea are acidified with phosphoric acid to remove endogenous CO2, and are subsequently incubated with urease to convert the urea present in the plasma samples into CO2. The 13C enrichment of the generated CO2 is analysed by means of GC-IRMS. This method allows measurement of the molar percentage excess of [13C]urea to an accuracy of 0.02%. 3. Reproducibility studies showed that the sample processing procedure [within-run coefficient of variation (CV) < 2.8% and between-run CV < 8.8%] and the GC-IRMS analysis (within-day CV < 1.3% and between-day CV < 1.3%) could be repeated with good reproducibility. 4. In clinical urea kinetic studies in a healthy subject and in a renal failure patient without residual renal function, reproducible values of the distribution volume, production rate and clearance of urea were determined using minimal amounts of [13C]urea (25-50 mg). 5. Because only low [13C]urea enrichments are needed in this urea dilution method using GC-IRMS analysis, the costs of urea kinetic studies are reduced considerably, especially in patients with renal failure.

A perfusion study of the handling of urea and urea analogues by the gills of the dogfish shark (Squalus acanthias).

PubMed

Wood, Chris M; Liew, Hon Jung; De Boeck, Gudrun; Walsh, Patrick J

2013-01-01

The branchial mechanism of urea retention in elasmobranchs was investigated using an in vitro isolated-perfused head preparation, as well as in vivo samples, in the spiny dogfish shark. Both in vivo and in control saline perfusions containing 350 mmol L(-1) urea, calculated intracellular urea concentrations in gill epithelial cells were close to extracellular concentrations. Urea efflux to the external water fell only non-significantly, and calculated gill intracellular urea concentration did not change when perfusate urea concentration was reduced from 350 to 175 mmol L(-1) with osmotic compensation by 175 mmol L(-1) mannitol. However, when the urea analogues thiourea or acetamide were present in the perfusate at concentrations equimolar (175 mmol L(-1)) to those of urea (175 mmol L(-1)), urea efflux rates were increased 4-fold and 6.5-fold respectively, and calculated gill intracellular urea concentrations were depressed by about 55%. Analogue efflux rates were similar to urea efflux rates. Previous studies have argued that either the basolateral or apical membranes provided the limiting permeability barrier, and/or that a back-transporter on the basolateral membranes of gill cells is responsible for urea retention. The present results provide new evidence that the apical membrane is the limiting factor in maintaining gill urea impermeability, and raise the prospect that a urea back-transporter, which can be competitively inhibited by thiourea and acetamide, operates at the apical membrane.

Isotope ratio mass spectrometry (IRMS) versus laser-assisted ratio analyzer (LARA): a comparative study using two doses of.

PubMed

Savarino, V; Landi, F; Dulbecco, P; Ricci, C; Tessieri, L; Biagini, R; Gatta, L; Miglioli, M; Celle, G; Vaira, D

2000-11-01

This study was carried out to compare the measurements and the diagnostic accuracy of the traditional expensive IRMS and the new economical LARA system using two doses of [13C]urea + two different test meals in patients undergoing upper gastrointestinal endoscopy, both before and after anti-Helicobacter treatment. A total of 354 dyspeptic patients underwent endoscopy with gastric biopsies to diagnose H. pylori infection by CLO-test and histology. No patients had taken antibiotics, bismuth, or antisecretory drugs in the 4 weeks before testing. After overnight fasting, breath samples were collected simultaneously in both plastic and glass tubes at baseline and at 30 and 60 min after urea ingestion. In 237 patients 100 mg [13C]urea + Ensure and in 117 patients 75 mg [13C]urea + citric acid were given. The test was also performed with the two urea dosages and meals in 67 and 64 infected patients, respectively, four weeks after anti-Helicobacter therapy. H. pylori was considered eradicated when both biopsy-based tests were negative. A delta value >5 per thousand was considered positive. Breath samples with insufficient CO2 levels at both 30 and 60 min were excluded from final analysis (N = 37 in pre- and N = 8 in posttreatment). There was excellent agreement between overall delta values of the two machines with both [13C]urea 100 mg + Ensure and [13C]urea 75 mg + citric acid. The 95% CI of the difference against the mean was wider with the former (mean -1.3, +6.3, and -9.4) than with the latter urea dosage and test meal (mean -1.2, +5.2 and -8.1). LARA and IRMS were equally effective (P = NS) in distinguishing infected from uninfected patients before therapy using both doses of [13C]urea and test meals (sensitivity ranged from 95% to 99% and specificity from 95% to 97%). This good performance was maintained in the posttreatment phase (sensitivity ranged from 90% to 100% and specificity from 90% to 97%), without any statistical difference among the various combinations (P = NS). The LARA system is a valid alternative to IRMS in the diagnosis of H. pylori infection. Both machines provide highly reliable results after 30 min, so that the 60 min sample can be avoided. The dose of 75 mg + citric acid suffices to ensure an accurate UBT. The test performed with both devices and [13C]urea dosages is very effective also for posttherapy evaluation of H. pylori status.

Protective effect of Heliotropium eichwaldi against cisplatin-induced nephrotoxicity in mice.

PubMed

Sharma, Surendra Kr; Goyal, Naveen

2012-05-01

The aim of the present study was to evaluate the nephroprotective effect of methanolic extract of Heliotropium eichwaldii (MHE) in mice with cisplatin-induced acute renal damage. Nephrotoxicity was induced by a single intraperitoneal injection of cisplatin (16mg/kg). Swiss albino mice were injected with vehicle, cisplatin, cisplatin plus MHE 200 mg/kg and cisplatin plus MHE 400mg/kg, respectively. MHE was administered for 7 d at a dose of 200 and 400 mg/kg per day orally starting 4 d before cisplatin injection. Animals were sacrificed 3d after treatment and blood as well as kidney tissue was isolated and analyzed. The various parameters such as blood urea nitrogen (BUN), serum creatinine (CRE), malondialdehyde (MDA), and catalase (CAT) and superoxide dismutase (SOD) activities were analyzed. MHE treatment significantly reduced BUN and serum CRE levels elevated by cisplatin administration (P<0.05). Also, it significantly attenuated cisplatin-induced increase in MDA level and improved the decreased CAT and SOD activities in renal cortical homogenates (P<0.05). Additionally, histopathological examination and scoring showed that MHE markedly ameliorated cisplatin-induced renal tubular necrosis. MHE can be considered a potential candidate for protection of nephrotoxicity induced by cisplatin.

Remnant B-cell-stimulative and anti-oxidative effects of Persea americana fruit extract studied in rats introduced into streptozotocin - induced hyperglycaemic state.

PubMed

Rao, U S Mahadeva; Adinew, Bizuneh

2011-01-01

Insulin-stimulative and anti-oxidative effects of Persea americana fruit extract were evaluated using streptozotocin (STZ). Ethanol extract of P. americana in the concentration of 300 mg/kg body weight/rat /day was orally administered to rats introduced into STZ-induced hyperglycaemic state for a period of 30 days. After the treatment with avocado fruit extract, the elevated levels of blood glucose, glycosylated haemoglobin, blood urea and serum creatinine seen in the hyperglycaemic rats, reverted back to near normal. Similarly, significantly decreased plasma insulin and haemoglobin levels went back to near normal after the treatment, suggesting the insulin-stimulative effect of P. americana fruit. Determination of thiobarbituric acid reactive substances (TBARS), hydroperoxides and both enzymatic and non-enzymatic antioxidants, confirmed the anti-oxidative potential of avocado fruit extract which, in turn, might be responsible for its hypoglycaemic potential. Changes in activities of enzymes such as serum aspartate transaminase (AST), serum alanine transaminase (ALT), and serum alkaline phosphatase (ALP) seen in the control and experimental rats, revealed the tissue-protective nature of Persea americana fruits, while all of the analysed biochemical parameters were comparable to those obtained with gliclazide as a standard reference drug.

Hyperammonemic syndrome after Roux-en-Y gastric bypass.

PubMed

Fenves, Andrew Z; Shchelochkov, Oleg A; Mehta, Ankit

2015-04-01

Hyperammonemic encephalopathy is an uncommon but severe complication of the Roux-en-Y gastric bypass surgery for obesity. Mechanisms underlying this complication are incompletely understood, resulting in delayed recognition and management. This study evaluated common laboratory findings and possible etiology of hyperammonemic encephalopathy after successful Roux-en-Y gastric bypass surgery. A retrospective review of 20 patients identified through our own clinical practice was conducted, with the addition of similar cases from other institutions identified through the review of literature. Patients presenting with hyperammonemic encephalopathy after Roux-en-Y gastric bypass surgery presented with overlapping clinical and laboratory findings. Common features included: (1) weight loss following successful Roux-en-Y gastric bypass for obesity; (2) hyperammonemic encephalopathy accompanied by elevated plasma glutamine levels; (3) absence of cirrhosis; (4) hypoalbuminemia; and (5) low plasma zinc levels. The mortality rate was 50%. Ninety-five percent of patients were women. Three patients were diagnosed with proximal urea cycle disorders. One patient experienced improvement in the hyperammonemia after surgical correction of spontaneous splenorenal shunt. Hyperammonemic encephalopathy after Roux-en-Y gastric bypass surgery is a newly recognized, potentially fatal syndrome with diverse pathophysiologic mechanisms encompassing genetic and nongenetic causes. © 2015 The Obesity Society.

Influence of milk urea concentration on fractional urea disappearance rate from milk to blood plasma in dairy cows.

PubMed

Spek, J W; Dijkstra, J; Bannink, A

2016-05-01

The relationship between milk urea nitrogen (MUN; mg of N/dL) and urinary N excretion is affected, among others, by diurnal dynamics in MUN, which in turn is largely influenced by feed intake pattern and characteristics of urea transfer from blood plasma to milk and vice versa. This study aimed to obtain insight in urea transfer characteristics within the mammary gland and from the mammary gland to blood plasma in dairy cows at various concentrations of plasma urea nitrogen (PUN; mg of N/dL) and MUN. Urea transfer from milk to blood plasma and urea transfer within the mammary gland itself was evaluated in a 4×4 Latin square design using 4 lactating multiparous Holstein-Friesian cows (milk production of 39.8±4.70kg/d and 90±3.9 d in milk). Treatments consisted of 4 primed continuous intravenous urea infusions of 0, 5, 10, and 15g of urea/h. Boluses of [(15)N(15)N]urea were injected in cistern milk at 20, 60, and 100 min before the 1700h milking. Milk was collected in portions of approximately 2 L at the 1700h milking. Milk samples were analyzed for urea and enrichment of (15)N-urea. Results from one cow were discarded because of leakage of milk from the teats after injection of boluses of [(15)N(15)N]urea. Increasing urea infusion rate linearly increased PUN from 11.4 (0g of urea/h) to 25.9mg/dL (15g of urea/h) and MUN from 10.3 (0g of urea/h) to 23.5 (15g of urea/h) mg of N/dL. The percentage of injected [(15)N(15)N]urea recovered from milk at the time of injection was not affected by urea infusion rate and varied between 65.1 and 73.0%, indicating that a substantial portion of injected [(15)N(15)N]urea was not accounted for by collected milk. The estimated fractional disappearance rate of (15)N-urea from milk to blood (Kurea; per hour) linearly increased from 0.429 (0g of urea/h) to 0.641 per hour (15g of urea/h). Cistern injected [(15)N(15)N]urea diffused within 20 min after injection toward alveoli milk. Calculations with the average Kurea estimated in this study show that 89% of an initial difference between PUN and MUN will have disappeared after 4 h. In conclusion, urea disappearance from milk in the mammary gland is substantial, as well as the intramammary urea exchange between cistern, duct, and alveoli milk. However, results have to be interpreted with caution given the lack of full recovery of dosed (15)N urea at time of injection. Information on Kurea is useful to quantify the effects of diurnal variation in PUN on MUN, which enhances the utility of MUN as an indicator for N excretion in urine. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Inhibition of post-traumatic septic proteolysis and ureagenesis and stimulation of hepatic acute-phase protein production by branched-chain amino acid TPN.

PubMed

Chiarla, C; Siegel, J H; Kidd, S; Coleman, B; Mora, R; Tacchino, R; Placko, R; Gum, M; Wiles, C E; Belzberg, H

1988-08-01

Previous studies have shown that severe sepsis after major trauma results in the reprioritization of release of hepatic acute-phase proteins (APP). They suggest competition for leucine for nutritional utilization may be responsible. To test this hypothesis, a branched-chain enriched (46.6%) amino acid mixture (BCAA) was administered on a prospective randomized basis with standard TPN therapy to 16 septic post-trauma patients. After sepsis was diagnosed, a randomized therapy (control-TPN or BCAA-TPN) was given for 12 days, or until death occurred. Total calories and amino acid nitrogen (N) administered were not different in the two groups (t-test) and q 8 h (347 study periods) amino acid clearances, urinary urea nitrogen excretion, muscle proteolysis from 3-methyl-histidine (3-MH) excretion, and standard indices of sepsis severity and hepatic function were measured, as well as platelets (PLAT), leucocytes (WBC), albumin (ALB), and six acute-phase proteins: C-reactive protein (CRP), alpha-1-antitrypsin (A1TRIP), fibrinogen (FIBRIN), alpha-2-macroglobulin (AMACRO), ceruloplasmin (CERUL), and transferrin (TRANS). Using Scheffé analysis of all contrasts the data showed: BCAA resulted in a fall in 24-hour urea N excretion (24.0 to 20.0 gm/24 hr) and in proteolysis (138 to 126 gm/24 hr) (p less than 0.0001). Prestudy CRP levels were all elevated, but compared to control where APP reprioritization occurred, over the initial 10 days of therapy BCAA patients had a more rapid fall in CRP with a more rapid rise in FIBRIN, TRANS, CERUL, ALBUMIN, AMACRO, and A1TRIP (all p less than 0.0001) relative to CRP. Also, the sepsis-reduced clearances of glutamine and glutamate, alanine, and proline were increased (p less than 0.0001) during BCAA even though urea nitrogen production was reduced (p less than 0.0001). The increase in leucine clearance with BCAA-enriched TPN was positively correlated (r2 = 0.601; p less than 0.0001) with the increase in the sum of all APP and ALB and was also associated with an increase both in FIBRIN and in platelets (p less than 0.0001). The BCAA-related increase in FIBRIN (9.1 to 11.9 mg/ml) occurred at the same time as a fall in prothrombin time (p less than 0.0001). BCAA-enriched TPN reduced proteolysis and amino acid catabolism and appeared to increase the levels of the more rapidly appearing anti-inflammatory and nutritional hepatic APP and formed coagulation elements in post-traumatic sepsis.

Survival after treatment with phenylacetate and benzoate for urea-cycle disorders.

PubMed

Enns, Gregory M; Berry, Susan A; Berry, Gerard T; Rhead, William J; Brusilow, Saul W; Hamosh, Ada

2007-05-31

The combination of intravenous sodium phenylacetate and sodium benzoate has been shown to lower plasma ammonium levels and improve survival in small cohorts of patients with historically lethal urea-cycle enzyme defects. We report the results of a 25-year, open-label, uncontrolled study of sodium phenylacetate and sodium benzoate therapy (Ammonul, Ucyclyd Pharma) in 299 patients with urea-cycle disorders in whom there were 1181 episodes of acute hyperammonemia. Overall survival was 84% (250 of 299 patients). Ninety-six percent of the patients survived episodes of hyperammonemia (1132 of 1181 episodes). Patients over 30 days of age were more likely than neonates to survive an episode (98% vs. 73%, P<0.001). Patients 12 or more years of age (93 patients), who had 437 episodes, were more likely than all younger patients to survive (99%, P<0.001). Eighty-one percent of patients who were comatose at admission survived. Patients less than 30 days of age with a peak ammonium level above 1000 micromol per liter (1804 microg per deciliter) were least likely to survive a hyperammonemic episode (38%, P<0.001). Dialysis was also used in 56 neonates during 60% of episodes and in 80 patients 30 days of age or older during 7% of episodes. Prompt recognition of a urea-cycle disorder and treatment with both sodium phenylacetate and sodium benzoate, in conjunction with other therapies, such as intravenous arginine hydrochloride and the provision of adequate calories to prevent catabolism, effectively lower plasma ammonium levels and result in survival in the majority of patients. Hemodialysis may also be needed to control hyperammonemia, especially in neonates and older patients who do not have a response to intravenous sodium phenylacetate and sodium benzoate. Copyright 2007 Massachusetts Medical Society.

Biochemical markers and neuropsychological functioning in distal urea cycle disorders.

PubMed

Waisbren, Susan E; Cuthbertson, David; Burgard, Peter; Holbert, Amy; McCarter, Robert; Cederbaum, Stephen

2018-02-08

Urea cycle disorders often present as devastating metabolic conditions, resulting in high mortality and significant neuropsychological damage, despite treatment. The Urea Cycle Disorders Longitudinal Study is a natural history study that collects data from regular clinical follow-up and neuropsychological testing. This report examines links between biochemical markers (ammonia, glutamine, arginine, citrulline) and primary neuropsychological endpoints in three distal disorders, argininosuccinic acid synthetase deficiency (ASD or citrullinemia type I), argininosuccinic acid lyase deficiency (ASA or ALD), and arginase deficiency (ARGD). Laboratory results and test scores from neuropsychological evaluations were assessed in 145 study participants, ages 3 years and older, with ASD (n = 64), ASA (n = 65) and ARGD (n = 16). Mean full scale IQ was below the population mean of 100 ± 15 for all groups: (ASD = 79 ± 24; ASA = 71 ± 21; ARGD = 65 ± 19). The greatest deficits were noted in visual performance and motor skills for all groups. While ammonia levels remain prominent as prognostic biomarkers, other biomarkers may be equally valuable as correlates of neuropsychological functioning. Cumulative exposure to the biomarkers included in the study proved to be highly sensitive indicators of neuropsychological outcomes, even when below the cut-off levels generally considered toxic. Blood levels of biomarkers obtained on the day of neuropsychological evaluations were not correlated with measures of functioning for any disorder in any domain. The importance of cumulative exposure supports early identification and confirms the need for well-controlled management of all biochemical abnormalities (and not just ammonia) that occur in urea cycle disorders.

Immunoglobulin and antibody levels in bronchoalveolar lavage fluid from symptomatic and asymptomatic pigeon breeders.

PubMed Central

Reynolds, S P; Edwards, J H; Jones, K P; Davies, B H

1991-01-01

Twenty-one symptomatic subjects with pigeon breeders' lung (PBL) and 10 asymptomatic pigeon breeders, with a similar exposure to pigeon antigens, underwent bronchoalveolar lavage. Total IgG, IgM and IgA in lavage fluid were determined as were specific antibody levels against antigens in pigeon serum and droppings. Results were converted to levels in epithelial lining fluid (ELF) using lavage and serum urea ratios. It was found that symptomatics represent a group that is hyperreactive to pigeon antigens compared with the asymptomatic group with significantly higher IgG, IgM, IgA levels as well as specific antibody levels against pigeon serum and droppings. Paired serum and ELF samples from 12 symptomatic subjects showed significantly elevated IgG, IgM and IgA levels in ELF compared with serum when values were expressed in terms of albumin. This strongly supports the concept of local production of immunoglobulins within the lung after inhaling immunogens as opposed to their diffusion from the vasculature. Results for IgA indicate that any putative protective role for this immunoglobulin is not valid in relation to the prevention of extrinsic allergic alveolitis. Analysis of smoking habits, lung immunoglobulins and response to inhalation challenge confirm the negative influence of smoking on total and functional lung immunoglobulins; however, levels in the ELF of ex-smokers suggest that the effect of smoking is not permanent. Smoking did not prevent responses to inhalation challenge. PMID:1934595

Improving Ammonium and Nitrate Release from Urea Using Clinoptilolite Zeolite and Compost Produced from Agricultural Wastes

PubMed Central

Omar, Latifah; Ahmed, Osumanu Haruna; Majid, Nik Muhamad Ab.

2015-01-01

Improper use of urea may cause environmental pollution through NH3 volatilization and NO3 − leaching from urea. Clinoptilolite zeolite and compost could be used to control N loss from urea by controlling NH4 + and NO3 − release from urea. Soil incubation and leaching experiments were conducted to determine the effects of clinoptilolite zeolite and compost on controlling NH4 + and NO3 − losses from urea. Bekenu Series soil (Typic Paleudults) was incubated for 30, 60, and 90 days. A soil leaching experiment was conducted for 30 days. Urea amended with clinoptilolite zeolite and compost significantly reduced NH4 + and NO3 − release from urea (soil incubation study) compared with urea alone, thus reducing leaching of these ions. Ammonium and NO3 − leaching losses during the 30 days of the leaching experiment were highest in urea alone compared with urea with clinoptilolite zeolite and compost treatments. At 30 days of the leaching experiment, NH4 + retention in soil with urea amended with clinoptilolite zeolite and compost was better than that with urea alone. These observations were because of the high pH, CEC, and other chemical properties of clinoptilolite zeolite and compost. Urea can be amended with clinoptilolite zeolite and compost to improve NH4 + and NO3 − release from urea. PMID:25793220

Nitrogen Fertilization Elevated Spatial Heterogeneity of Soil Microbial Biomass Carbon and Nitrogen in Switchgrass and Gamagrass Croplands

NASA Astrophysics Data System (ADS)

Jian, S.; Li, J.; Guo, C.; Hui, D.; Deng, Q.; Yu, C. L.; Dzantor, K. E.; Lane, C.

2017-12-01

Nitrogen (N) fertilizers are widely used to increase bioenergy crop yield but intensive fertilizations on spatial distributions of soil microbial processes in bioenergy croplands remains unknown. To quantify N fertilization effect on spatial heterogeneity of soil microbial biomass carbon (MBC) and N (MBN), we sampled top mineral horizon soils (0-15cm) using a spatially explicit design within two 15-m2 plots under three fertilization treatments in two bioenergy croplands in a three-year long fertilization experiment in Middle Tennessee, USA. The three fertilization treatments were no N input (NN), low N input (LN: 84 kg N ha-1 in urea) and high N input (HN: 168 kg N ha-1 in urea). The two crops were switchgrass (SG: Panicum virgatum L.) and gamagrass (GG: Tripsacum dactyloides L.). Results showed that N fertilizations little altered central tendencies of microbial variables but relative to LN, HN significantly increased MBC and MBC:MBN (GG only). HN possessed the greatest within-plot variances except for MBN (GG only). Spatial patterns were generally evident under HN and LN plots and much less so under NN plots. Substantially contrasting spatial variations were also identified between croplands (GG>SG) and among variables (MBN, MBC:MBN > MBC). No significant correlations were identified between soil pH and microbial variables. This study demonstrated that spatial heterogeneity is elevated in microbial biomass of fertilized soils likely by uneven fertilizer application, the nature of soil microbial communities and bioenergy crops. Future researchers should better match sample sizes with the heterogeneity of soil microbial property (i.e. MBN) in bioenergy croplands.

Effects of feeding and fasting on wolf blood and urine characteristics

USGS Publications Warehouse

DelGiudice, G.D.; Seal, U.S.; Mech, L.D.

1987-01-01

Feeding and fasting trials were conducted with 2 groups (A and B) of 4 gray wolves (Canis lupus) each during January 1980. The groups were fed for 9 days and fasted for 10 days in a cross-over design. Blood and urine samples and weight data were collected every 2-3 days during each trial. Hemoglobin (Hb) concentrations, red blood cell (RBC) counts, and hematocrits (HCT) were elevated in both groups during fasting. White blood cell (WBC) counts, serum urea nitrogen (SUN), triiodothyronine (T3), and insulin concentrations decreased during fasting in Groups A and B. Mean corpuscular hemoglobin concentration (MCHC), serum cholesterol, triglyceride, and iron (Fe) concentrations were diminished in fasted Group A wolves compared to fed Group B. Creatine phosphokinase (CPK) concentrations were elevated in fed Group A wolves. Serum creatinine (C) concentrations were reduced in both groups during feeding. Urinary urea: creatinine (U:C), potassium:creatine (K:C), and sodium:creatinine (Na:C, pooled Group A and B data) ratios decreased in fasted wolves. Differences were not found between fed and fasted wolves for mean corpuscular volume (MCV), serum cortisol, glucose, calcium (Ca), bilirubin, serum glutamate-oxaloacetate transaminase (SGOT), serum glutamate-pyruvate transaminase (SGOT), serum glutamate-pyruvate transaminase (SGPT), alkaline phosphatase, and luteinizing hormone (LH) concentrations, total iron binding capacity (TIBC), and urinary calcium: creatine (Ca:C) ratios. Analysis of multiple blood or urine samples collected from free-ranging wolves would be useful in enabling researches and managers to identify the nutritional status and general health of wolves over time.

Ancient Chinese Formula Qiong-Yu-Gao Protects Against Cisplatin-Induced Nephrotoxicity Without Reducing Anti-tumor Activity

PubMed Central

Teng, Zhi-Ying; Cheng, Xiao-Lan; Cai, Xue-Ting; Yang, Yang; Sun, Xiao-Yan; Xu, Jin-Di; Lu, Wu-Guang; Chen, Jiao; Hu, Chun-Ping; Zhou, Qian; Wang, Xiao-Ning; Li, Song-Lin; Cao, Peng

2015-01-01

Cisplatin is a highly effective anti-cancer chemotherapeutic agent; however, its clinical use is severely limited by serious side effects, of which nephrotoxicity is the most important. In this study, we investigated whether Qiong-Yu-Gao (QYG), a popular traditional Chinese medicinal formula described 840 years ago, exhibits protective effects against cisplatin-induced renal toxicity. Using a mouse model of cisplatin-induced renal dysfunction, we observed that pretreatment with QYG attenuated cisplatin-induced elevations in blood urea nitrogen and creatinine levels, ameliorated renal tubular lesions, reduced apoptosis, and accelerated tubular cell regeneration. Cisplatin-mediated elevations in tumor necrosis factor alpha (TNF-α) mRNA, interleukin-1 beta (IL-1β) mRNA, and cyclooxygenase-2 (COX-2) protein in the kidney were also significantly suppressed by QYG treatment. Furthermore, QYG reduced platinum accumulation in the kidney by decreasing the expression of copper transporter 1 and organic cation transporter 2. An in vivo study using implanted Lewis lung cancer cells revealed that concurrent administration of QYG and cisplatin did not alter the anti-tumor activity of cisplatin. Our findings suggest that the traditional Chinese medicinal formula QYG inhibits cisplatin toxicity by several mechanisms that act simultaneously, without compromising its therapeutic efficacy. Therefore, QYG may be useful in the clinic as a protective agent to prevent cisplatin-induced nephrotoxicity. PMID:26510880

Biodegradation of sulfosulphuron in agricultural soil by Trichoderma sp.

PubMed

Yadav, U; Choudhury, P P

2014-11-01

Sulfosulphuron-degrading fungus was isolated by enrichment technique from the sulfosulphuron-contaminated soil of wheat rhizosphere. To assess the biodegradation potential of isolated Trichoderma sp., minimal potato dextrose agar broth with different levels of sulfosulphuron (up to 2 g l(-1) ) was evaluated in the growth and biotransformation experiments. ESI LC-MS/MS analysis revealed the presence of degradation products 2-amino-4,6-dimethoxypyrimidine (I) and 2-ethylsulfonyl imidazo{1,2-a} pyridine-3-sulfonamide-2-ethylsulfonyl imidazo{1,2-a} pyridine-3-sulfonamide (II) indicating the cleavage of the urea bridge and the presence of the by-product N-(4,6-dimethoxypyrimidin-2-yl)urea (III) indicating the degradation of sulfonylamide linkage. Two other metabolites, N-(4,6-dimethoxypyrimidin-2-yl)-N'-hydroxyurea (IV) and N, N'-bis(4,6-dimethoxypyrimidin-2-yl)urea (V), were also identified. From the previous reports, it was found that the degradation of sulfonyl urea herbicides took place through the chemical degradation of the sulfonylurea bridge followed by microbial degradation. During this investigation, Trichoderma sp. grew well with and degraded sulfosulphuron via both the decarboxylation on the sulphonyl urea bridge and the hydrolytic cleavage of the sulfonylamide linkage as demonstrated by the formation of metabolites. Trichoderma is nonphytopathogenic in nature, and some species of it restrict the growth of soil-dwelling phytopathogens. Therefore, it is a promising candidate for the decontamination of soil from sulfosulphuron residues. The degradation of sulfosulphuron by any individual fungus is being reported for the first time. Trichoderma sp. isolated from wheat-rhizospheric soil could survive in minimal broth rich in sulfosulphuron. Previous reports have described the complete degradation of any sulfonyl urea herbicides by micro-organisms only after the pH-dependent chemical hydrolysis of the sulfonyl urea bridge of the herbicide. This study demonstrates the novel result that the Trichoderma sp. utilized the sulfosulphuron as a sole carbon source and degraded it by cleaving sulfonyl urea bridge and sulfonylamide linkage. Thus, the application of Trichoderma sp., which is nonphytopathogenic, has the potential to decontaminate agricultural soil from sulfosulphuron load. © 2014 The Society for Applied Microbiology.

Urea adsorption by activated carbon prepared from palm kernel shell

NASA Astrophysics Data System (ADS)

Ooi, Chee-Heong; Sim, Yoke-Leng; Yeoh, Fei-Yee

2017-07-01

Dialysis treatment is crucial for patients suffer from renal failure. The dialysis system removes the uremic toxin to a safe level in a patient's body. One of the major limitations of the current hemodialysis system is the capability to efficiently remove uremic toxins from patient's body. Nanoporous materials can be applied to improve the treatment. Palm kernel shell (PKS) biomass generated from palm oil mills can be utilized to prepare high quality nanoporous activated carbon (AC) and applied for urea adsorption in the dialysis system. In this study, AC was prepared from PKS via different carbonization temperatures and followed by carbon dioxide gas activation processes. The physical and chemical properties of the samples were studied. The results show that the porous AC with BET surface areas ranging from 541 to 622 m2g-1 and with total pore volumes varying from 0.254 to 0.297 cm3g-1, are formed with different carbonization temperatures. The equilibrium constant for urea adsorption by AC samples carbonized at 400, 500 and 600 °C are 0.091, 0.287 and 0.334, respectively. The increase of carbonization temperatures from 400 to 600 °C resulted in the increase in urea adsorption by AC predominantly due to increase in surface area. The present study reveals the feasibility of preparing AC with good porosity from PKS and potentially applied in urea adsorption application.

Erythrocyte permeability to urea and water: comparative study in rodents, ruminants, carnivores, humans, and birds.

PubMed

Liu, Lifeng; Lei, Tianluo; Bankir, Lise; Zhao, Dan; Gai, Xiaodong; Zhao, Xuejian; Yang, Baoxue

2011-01-01

Mammalian erythrocytes exhibit high urea permeability (P (urea)) due to UT-B expression in their cytoplasmic membrane. This high P (urea) allows fast equilibration of urea in erythrocytes during their transit in the hyperosmotic renal medulla. It also allows more urea (in addition to that in plasma) to participate in counter-current exchange between ascending and descending vasa recta, thus improving the trapping of urea in the medulla and improving urine concentrating ability. To determine if P (urea) in erythrocytes is related to diet and urine concentrating ability, we measured P (urea) in erythrocytes from 11 different mammals and 5 birds using stopped-flow light scattering. Carnivores (dog, fox, cat) exhibited high P (urea) (in x10(-5) cm/s, 5.3 ± 0.6, 3.8 ± 0.5 and 2.8 ± 0.7, respectively). In contrast, herbivores (cow, donkey, sheep) showed much lower P (urea) (0.8 ± 0.2, 0.7 ± 0.2, 1.0 ± 0.1, respectively). Erythrocyte P (urea) in human (1.1 ± 0.2), and pig (1.5 ± 0.1), the two omnivores, was intermediate. Rodents and lagomorphs (mouse, rat, rabbit) had P (urea) intermediate between carnivores and omnivores (3.3 ± 0.4, 2.5 ± 0.3 and 2.4 ± 0.3, respectively). Birds that do not excrete urea and do not express UT-B in their erythrocytes had very low values (<0.1 × 10(-5) cm/s). In contrast to P (urea), water permeability, measured simultaneously, was relatively similar in all mammals. The species differences in erythrocytes P (urea) most probably reflect adaptation to the different types of diet and resulting different needs for concentrating urea in the urine.

Ammonia and greenhouse gas emissions from a subtropical wheat field under different nitrogen fertilization strategies.

PubMed

Liu, Shuai; Wang, Jim J; Tian, Zhou; Wang, Xudong; Harrison, Stephen

2017-07-01

Minimizing soil ammonia (NH 3 ) and nitrous oxide (N 2 O) emission factors (EFs) has significant implications in regional air quality and greenhouse gas (GHG) emissions besides nitrogen (N) nutrient loss. The aim of this study was to investigate the impacts of different N fertilizer treatments of conventional urea, polymer-coated urea, ammonia sulfate, urease inhibitor (NBPT, N-(n-butyl) thiophosphoric triamide)-treated urea, and nitrification inhibitor (DCD, dicyandiamide)-treated urea on emissions of NH 3 and GHGs from subtropical wheat cultivation. A field study was established in a Cancienne silt loam soil. During growth season, NH 3 emission following N fertilization was characterized using active chamber method whereas GHG emissions of N 2 O, carbon dioxide (CO 2 ), and methane (CH 4 ) were by passive chamber method. The results showed that coated urea exhibited the largest reduction (49%) in the EF of NH 3 -N followed by NBPT-treated urea (39%) and DCD-treated urea (24%) over conventional urea, whereas DCD-treated urea had the greatest suppression on N 2 O-N (87%) followed by coated urea (76%) and NBPT-treated urea (69%). Split fertilization of ammonium sulfate-urea significantly lowered both NH 3 -N and N 2 O-N EF values but split urea treatment had no impact over one-time application of urea. Both NBPT and DCD-treated urea treatments lowered CO 2 -C flux but had no effect on CH 4 -C flux. Overall, application of coated urea or urea with NPBT or DCD could be used as a mitigation strategy for reducing NH 3 and N 2 O emissions in subtropical wheat production in Southern USA. Copyright © 2017. Published by Elsevier B.V.

[Adsorbent effect of activated carbon on small molecular uremic toxin and its influence factors].

PubMed

Yang, Bo; Jiang, Yun-sheng; Li, Jun

2003-06-01

To analyze the adsorbent effect of activated carbon on uremic toxin and its influence factors. Uremic toxins (urea, creatinine and uric acid) were dissolved in the distilled water to obtain uremic toxic solution. Activated carbon was added to the solution, and the concentrations of uremic toxins were measured at different time spots. To determine the influence factors, some possible related materials, such as bile, amino acid, Ringer's, solution of glucose, HCl or NaOH respectively were added simultaneously. The concentrations of toxins in uremic toxic solution decreased 5 min after adding the activated carbon. The concentration of urea was the lowest at 30 min, but it increased after 50 min; while the concentrations of creatinine and uric acid reached the lowest level from 10 to 30 min after adding the activated carbon, and maintained at the same level after that. The bile, amino acid, electrolyte, glucose and pH value did not influence the adsorption of uric acid significantly, but they influenced the adsorption of urea and creatinine. Bile and amino acid influenced the concentration of urea remarkably, following glucose, NaOH and HCl. The effect of pH 2.0 solution on the creatinine concentration was the most significant, following glucose. Activated carbon has adsorptive effect on uremic toxins, but its adsorptive effect decreases as time goes on. Bile, glucose, amino acid, NaOH and HCl can affect the adsorptive effect of activated carbon on uremic toxins to some extent.

A perfusion study of the handling of urea and urea analogues by the gills of the dogfish shark (Squalus acanthias)

PubMed Central

Liew, Hon Jung; De Boeck, Gudrun; Walsh, Patrick J.

2013-01-01

The branchial mechanism of urea retention in elasmobranchs was investigated using an in vitro isolated-perfused head preparation, as well as in vivo samples, in the spiny dogfish shark. Both in vivo and in control saline perfusions containing 350 mmol L−1 urea, calculated intracellular urea concentrations in gill epithelial cells were close to extracellular concentrations. Urea efflux to the external water fell only non-significantly, and calculated gill intracellular urea concentration did not change when perfusate urea concentration was reduced from 350 to 175 mmol L−1 with osmotic compensation by 175 mmol L−1 mannitol. However, when the urea analogues thiourea or acetamide were present in the perfusate at concentrations equimolar (175 mmol L−1) to those of urea (175 mmol L−1), urea efflux rates were increased 4-fold and 6.5-fold respectively, and calculated gill intracellular urea concentrations were depressed by about 55%. Analogue efflux rates were similar to urea efflux rates. Previous studies have argued that either the basolateral or apical membranes provided the limiting permeability barrier, and/or that a back-transporter on the basolateral membranes of gill cells is responsible for urea retention. The present results provide new evidence that the apical membrane is the limiting factor in maintaining gill urea impermeability, and raise the prospect that a urea back-transporter, which can be competitively inhibited by thiourea and acetamide, operates at the apical membrane. PMID:23638369

Artificial intelligence: a new approach for prescription and monitoring of hemodialysis therapy.

PubMed

Akl, A I; Sobh, M A; Enab, Y M; Tattersall, J

2001-12-01

The effect of dialysis on patients is conventionally predicted using a formal mathematical model. This approach requires many assumptions of the processes involved, and validation of these may be difficult. The validity of dialysis urea modeling using a formal mathematical model has been challenged. Artificial intelligence using neural networks (NNs) has been used to solve complex problems without needing a mathematical model or an understanding of the mechanisms involved. In this study, we applied an NN model to study and predict concentrations of urea during a hemodialysis session. We measured blood concentrations of urea, patient weight, and total urea removal by direct dialysate quantification (DDQ) at 30-minute intervals during the session (in 15 chronic hemodialysis patients). The NN model was trained to recognize the evolution of measured urea concentrations and was subsequently able to predict hemodialysis session time needed to reach a target solute removal index (SRI) in patients not previously studied by the NN model (in another 15 chronic hemodialysis patients). Comparing results of the NN model with the DDQ model, the prediction error was 10.9%, with a not significant difference between predicted total urea nitrogen (UN) removal and measured UN removal by DDQ. NN model predictions of time showed a not significant difference with actual intervals needed to reach the same SRI level at the same patient conditions, except for the prediction of SRI at the first 30-minute interval, which showed a significant difference (P = 0.001). This indicates the sensitivity of the NN model to what is called patient clearance time; the prediction error was 8.3%. From our results, we conclude that artificial intelligence applications in urea kinetics can give an idea of intradialysis profiling according to individual clinical needs. In theory, this approach can be extended easily to other solutes, making the NN model a step forward to achieving artificial-intelligent dialysis control.

Urea Synthesis and Excretion in Aedes aegypti Mosquitoes Are Regulated by a Unique Cross-Talk Mechanism

PubMed Central

Isoe, Jun; Scaraffia, Patricia Y.

2013-01-01

Aedes aegypti mosquitoes do not have a typical functional urea cycle for ammonia disposal such as the one present in most terrestrial vertebrates. However, they can synthesize urea by two different pathways, argininolysis and uricolysis. We investigated how formation of urea by these two pathways is regulated in females of A. aegypti. The expression of arginase (AR) and urate oxidase (UO), either separately or simultaneously (ARUO) was silenced by RNAi. The amounts of several nitrogen compounds were quantified in excreta using mass spectrometry. Injection of mosquitoes with either dsRNA-AR or dsRNA-UO significantly decreased the expressions of AR or UO in the fat body (FB) and Malpighian tubules (MT). Surprisingly, the expression level of AR was increased when UO was silenced and vice versa, suggesting a cross-talk regulation between pathways. In agreement with these data, the amount of urea measured 48 h after blood feeding remained unchanged in those mosquitoes injected with dsRNA-AR or dsRNA-UO. However, allantoin significantly increased in the excreta of dsRNA-AR-injected females. The knockdown of ARUO mainly led to a decrease in urea and allantoin excretion, and an increase in arginine excretion. In addition, dsRNA-AR-injected mosquitoes treated with a specific nitric oxide synthase inhibitor showed an increase of UO expression in FB and MT and a significant increase in the excretion of nitrogen compounds. Interestingly, both a temporary delay in the digestion of a blood meal and a significant reduction in the expression of several genes involved in ammonia metabolism were observed in dsRNA-AR, UO or ARUO-injected females. These results reveal that urea synthesis and excretion in A. aegypti are tightly regulated by a unique cross-talk signaling mechanism. This process allows blood-fed mosquitoes to regulate the synthesis and/or excretion of nitrogen waste products, and avoid toxic effects that could result from a lethal concentration of ammonia in their tissues. PMID:23755226

Increased Erythrocytes By-Products of Arginine Catabolism Are Associated with Hyperglycemia and Could Be Involved in the Pathogenesis of Type 2 Diabetes Mellitus

PubMed Central

Ramírez-Zamora, Serafín; Méndez-Rodríguez, Miguel L.; Olguín-Martínez, Marisela; Sánchez-Sevilla, Lourdes; Quintana-Quintana, Miguel; García-García, Norberto; Hernández-Muñoz, Rolando

2013-01-01

Diabetes mellitus (DM) is a worldwide disease characterized by metabolic disturbances, frequently associated with high risk of atherosclerosis and renal and nervous system damage. Here, we assessed whether metabolites reflecting oxidative redox state, arginine and nitric oxide metabolism, are differentially distributed between serum and red blood cells (RBC), and whether significant metabolism of arginine exists in RBC. In 90 patients with type 2 DM without regular treatment for diabetes and 90 healthy controls, paired by age and gender, we measured serum and RBC levels of malondialdehyde (MDA), nitrites, ornithine, citrulline, and urea. In isolated RBC, metabolism of L-[14C]-arginine was also determined. In both groups, nitrites were equally distributed in serum and RBC; citrulline predominated in serum, whereas urea, arginine, and ornithine were found mainly in RBC. DM patients showed hyperglycemia and increased blood HbA1C, and increased levels of these metabolites, except for arginine, significantly correlating with blood glucose levels. RBC were observed to be capable of catabolizing arginine to ornithine, citrulline and urea, which was increased in RBC from DM patients, and correlated with an increased affinity for arginine in the activities of putative RBC arginase (Km = 0.23±0.06 vs. 0.50±0.13 mM, in controls) and nitric oxide synthase (Km = 0.28±0.06 vs. 0.43±0.09 mM, in controls). In conclusion, our results suggest that DM alters metabolite distribution between serum and RBC, demonstrating that RBC regulate serum levels of metabolites which affect nitrogen metabolism, not only by transporting them but also by metabolizing amino acids such as arginine. Moreover, we confirmed that urea can be produced also by human RBC besides hepatocytes, being much more evident in RBC from patients with type 2 DM. These events are probably involved in the specific physiopathology of this disease, i.e., endothelial damage and dysfunction. PMID:23826148

Association of different biomarkers of renal function with D-dimer levels in patients with type 1 diabetes mellitus (renal biomarkers and D-dimer in diabetes).

PubMed

Domingueti, Caroline Pereira; Fóscolo, Rodrigo Bastos; Dusse, Luci Maria S; Reis, Janice Sepúlveda; Carvalho, Maria das Graças; Gomes, Karina Braga; Fernandes, Ana Paula

2018-02-01

Objective This study aimed to evaluate the association between different renal biomarkers with D-Dimer levels in diabetes mellitus (DM1) patients group classified as: low D-Dimer levels (< 318 ng/mL), which included first and second D-Dimer tertiles, and high D-Dimer levels (≥ 318 ng/mL), which included third D-Dimer tertile. Materials and methods D-Dimer and cystatin C were measured by ELISA. Creatinine and urea were determined by enzymatic method. Estimated glomerular filtration rate (eGFR) was calculated using CKD-EPI equation. Albuminuria was assessed by immunoturbidimetry. Presence of renal disease was evaluated using each renal biomarker: creatinine, urea, cystatin C, eGFR and albuminuria. Bivariate logistic regression analysis was performed to assess which renal biomarkers are associated with high D-Dimer levels and odds ratio was calculated. After, multivariate logistic regression analysis was performed to assess which renal biomarkers are associated with high D-Dimer levels (after adjusting for sex and age) and odds ratio was calculated. Results Cystatin C presented a better association [OR of 9.8 (3.8-25.5)] with high D-Dimer levels than albuminuria, creatinine, eGFR and urea [OR of 5.3 (2.2-12.9), 8.4 (2.5-25.4), 9.1 (2.6-31.4) and 3.5 (1.4-8.4), respectively] after adjusting for sex and age. All biomarkers showed a good association with D-Dimer levels, and consequently, with hypercoagulability status, and cystatin C showed the best association among them. Conclusion Therefore, cystatin C might be useful to detect patients with incipient diabetic kidney disease that present an increased risk of cardiovascular disease, contributing to an early adoption of reno and cardioprotective therapies.

Effect of nitrogen supplementation on urea kinetics and microbial use of recycled urea in steers consuming corn-based diets.

PubMed

Brake, D W; Titgemeyer, E C; Jones, M L; Anderson, D E

2010-08-01

We studied the effects of supplementing N as distillers dried grains with solubles (DDGS) or urea to steers consuming corn-based diets. Six ruminally and duodenally cannulated steers (244 kg) were used in 2 concurrent 3 x 3 Latin squares and fed 1 of 3 corn-based diets: control (10.2% CP), urea (13.3% CP), or DDGS (14.9% CP). Periods were 14 d, with 9 d for adaptation and 5 d for collection of urine and feces. Urinary (15)N(15)N-urea enrichments, resulting from venous infusions of (15)N(15)N-urea, were used to measure urea kinetics. Dry matter intake (6.0 kg/d) was not affected by treatment, but N intake differed (99, 151, and 123 g/d for the control, DDGS, and urea treatments, respectively). Urea-N synthesis tended to be greater (P = 0.09) for DDGS (118 g/d) than for the control treatment (52 g/d), with the urea treatment (86 g/d) being intermediate. Urea-N excreted in the urine was greater (P < 0.03) for the DDGS (35 g/d) and urea treatments (29 g/d) than for the control treatment (13 g/d). Gastrointestinal entry of urea-N was not statistically different among treatments (P = 0.25), but was numerically greatest for DDGS (83 g/d), intermediate for urea (57 g/d), and least for the control (39 g/d). The amount of urea-N returned to the ornithine cycle tended to be greater (P = 0.09) for the DDGS treatment (47 g/d) than for the urea (27 g/d) or control treatment (16 g/d). The fraction of recycled urea-N that was apparently used for anabolism tended (P = 0.14) to be greater for the control treatment (0.56) than for the DDGS treatment (0.31), with the urea treatment (0.45) being intermediate, but no differences were observed among treatments in the amount of urea-N used for anabolism (P = 0.66). Urea kinetics in cattle fed grain-based diets were largely related to the amount of N consumed. The percentage of urea production that was captured by ruminal bacteria was greater (P < 0.03) for the control treatment (42%) than for the DDGS (25%) or urea treatment (22%), but the percentage of duodenal microbial N flow that was derived from recycled urea-N tended (P = 0.10) to be greater for the DDGS treatment (35%) than for the urea (22%) or control treatment (17%). Thus, ruminal microbes were more dependent on N recycling when the protein supplement was largely resistant to ruminal degradation.

Effects of high ambient temperature on urea-nitrogen recycling in lactating dairy cows.

PubMed

Obitsu, Taketo; Kamiya, Mitsuru; Kamiya, Yuko; Tanaka, Masahito; Sugino, Toshihisa; Taniguchi, Kohzo

2011-08-01

Effects of exposure to hot environment on urea metabolism were studied in lactating Holstein cows. Four cows were fed ad libitum a total mixed ration and housed in a temperature-controlled chamber at constant moderate (18°C) or high (28°C) ambient temperatures in a cross-over design. Urea nitrogen (N) kinetics was measured by determining urea isotopomer in urine after single injection of [(15) N(2) ]urea into the jugular vein. Both dry matter intake and milk yield were decreased under high ambient temperature. Intakes of total N and digestible N were decreased under high ambient temperature but urinary urea-N excretion was increased. The ratio of urea-N production to digestible N was increased, whereas the proportion of gut urea-N entry to urea-N production tended to be decreased under high ambient temperature. Neither return to the ornithine cycle, anabolic use nor fecal excretion of urea-N recycled to the gut was affected by ambient temperature. Under high ambient temperature, renal clearance of plasma urea was not affected but the gut clearance was decreased. Increase of urea-N production and reduction of gut urea-N entry, in relative terms, were associated with increased urinary urea-N excretion of lactating dairy cows in higher thermal environments. 2011 The Authors. Animal Science Journal © 2011 Japanese Society of Animal Science.

Possible protective effect of the algae spirulina against nephrotoxicity induced by cyclosporine A and/or gamma radiation in rats.

PubMed

Aziz, Maha M; Eid, Nihad I; Nada, Ahmed S; Amin, Nour El-Din; Ain-Shoka, Afaf A

2018-03-01

The present study was conducted to evaluate the possible protective role of the algae spirulina (Sp) against nephrotoxicity and oxidative stress which are the main secondary effects induced by the immunosuppressant drug CSA and/or ionizing radiation. In this study, male rats were given Sp (1 g/kg) either for 15 days before irradiation (6.5 Gy) or 5 days before and 10 days concomitant with CSA (25 mg/kg). Markers used to assess renal injury included serum creatinine, urea, glucose, albumin, protein, and lipid profile as well as kidney content of reduced glutathione (GSH); lipid peroxidation (thiobarbituric acid reactive substances (TBARS)); nitrite and superoxide dismutase (SOD) activity. In addition, some trace elements (Zn and Mg) were estimated in kidney. Apoptosis was assessed by immunohistochemical estimation of caspase-3 expression in addition to histopathological examination. Results revealed that gamma radiation and/or CSA induced elevation in urea, creatinine, lipids, and glucose while decreasing albumin and protein levels. There was a noticeable increase in kidney content of GSH, TBARS, and nitrite. Meanwhile, profound decrease in kidney SOD activity was observed. Treatment with Sp significantly reversed the changes induced by CSA and/or gamma radiation in renal function tests. Spirulina also ameliorated kidney oxidative stress through decreasing GSH, TBARS, and nitrite kidney content while increasing SOD activity. Histopathological examination further confirmed Sp protective efficacy. Moreover, kidney caspase-3 expression that was triggered by CSA and/or gamma radiation was decreased. In conclusion, spirulina can be regarded as a promising renoprotective natural agent against renal injury induced by CSA and/or gamma radiation.

Characterization of urea transport in Bufo arenarum oocytes.

PubMed

Silberstein, Claudia; Zotta, Elsa; Ripoche, Pierre; Ibarra, Cristina

2003-07-01

Xenopus laevis oocytes have been extensively used for expression cloning, structure/function relationships, and regulation analysis of transporter proteins. Urea transporters have been expressed in Xenopus oocytes and their properties have been described. In order to establish an alternative system in which urea transporters could be efficiently expressed and studied, we determined the urea transport properties of ovarian oocytes from Bufo arenarum, a toad species common in Argentina. Bufo oocytes presented a high urea permeability of 22.3 x 10(-6) cm/s, which was significantly inhibited by the incubation with phloretin. The urea uptake in these oocytes was also inhibited by mercurial reagents, and high-affinity urea analogues. The urea uptake was not sodium dependent. The activation energy was 3.2 Kcal/mol, suggesting that urea movement across membrane oocytes may be through a facilitated urea transporter. In contrast, Bufo oocytes showed a low permeability for mannitol and glycerol. From these results, we propose that one or several specific urea transporters are present in ovarian oocytes from Bufo arenarum. Therefore, these oocytes cannot be used in expression studies of foreign urea transporters. The importance of Bufo urea transporter is not known but could be implicated in osmotic regulation during the laying of eggs in water. Copyright 2003 Wiley-Liss, Inc.

Exploring the Counteracting Mechanism of Trehalose on Urea Conferred Protein Denaturation: A Molecular Dynamics Simulation Study.

PubMed

Paul, Subrata; Paul, Sandip

2015-07-30

To provide the underlying mechanism of the inhibiting effect of trehalose on the urea denatured protein, we perform classical molecular dynamics simulations of N-methylacetamide (NMA) in aqueous urea and/or trehalose solution. The site-site radial distribution functions and hydrogen bond properties indicate in binary urea solution the replacement of NMA-water hydrogen bonds by NMA-urea hydrogen bonds. On the other hand, in ternary urea and trehalose solution, trehalose does not replace the NMA-urea hydrogen bonds significantly; rather, it forms hydrogen bonds with the NMA molecule. The calculation of a preferential interaction parameter shows that, at the NMA surface, trehalose molecules are preferred and the preference for urea decreases slightly in ternary solution with respect to the binary solution. The exclusion of urea molecules in the ternary urea-NMA-trehalose system causes alleviation in van der Waals interaction energy between urea and NMA molecules. Our findings also reveal the following: (a) trehalose and urea induced second shell collapse of water structure, (b) a reduction in the mean trehalose cluster size in ternary solution, and (c) slowing down of translational motion of solution species in the presence of osmolytes. Implications of these results for the molecular explanations of the counteracting mechanism of trehalose on urea induced protein denaturation are discussed.

Investigation of Risk Factors Affecting Lactate Levels in Japanese Patients Treated with Metformin.

PubMed

Yokoyama, Shota; Tsuji, Hideyuki; Hiraoka, Sachiko; Nishihara, Masayuki

2016-01-01

Metformin is a biguanaide antidiabetic drug used worldwide, and its effectiveness and benefits have already been established. However, the safety of high doses of metformin in Japanese patients, especially in elderly patients with a decreased renal function, remains unclear. Among the side effects of metformin, lactate acidosis is the most problematic due to a high mortality rate. Therefore, we assessed plasma lactate levels in metformin-treated patients to identify independent risk factors for hyperlactemia. 290 outpatients receiving various doses of metformin at our hospital were enrolled between March and July 2014. Serum electrolytes, Cre (creatinine), BUN (blood urea nitrogen), UA (uric acid), HbA1c (hemoglobin A1c), and lactate levels were investigated. Lactate levels did not significantly differ between the elderly (≥75 years) and non-elderly (<75 years) groups. Patients in the elderly group had a significantly lower daily metformin dose and estimated glomerular filtration rate (eGFR), compared with the non-elderly group (both p<0.005). Between with and without hyperlactemia groups, no significant differences were observed in either Cre or age. On the other hand, patients with hyperlactemia had a significantly higher dose of metformin than those without hyperlactemia (p<0.05). In this study, we found that old age and mildly impaired kidney function were not associated with increased lactate levels, and that a higher dose of metformin may be an independent risk factor for elevated lactate levels in Japanese patients.

Structure and effect of sarcosine on water and urea by using molecular dynamics simulations: Implications in protein stabilization.

PubMed

Kumar, Narendra; Kishore, Nand

2013-01-01

Sarcosine is one of the most important protecting osmolytes which is also known to counteract the denaturing effect of urea. We used molecular dynamics simulation methods to investigate the mechanism of protein stabilization and counteraction of urea by sarcosine. We found that sarcosine enhanced the tetrahedral structure of water and strengthened its hydrogen bonding network. We also found that sarcosine did not form clusters unlike glycine. Our results show strong interaction between sarcosine and urea molecules. Addition of sarcosine enhanced the urea-water structure and urea-water lifetime indicated an increase in the solvation of urea. These findings suggest that sarcosine indirectly stabilizes protein by enhancing water-water structure thus decreasing the hydrophobic effect and counteracts the effect of urea by increasing the solvation of urea and directly interacting with it leaving urea less available to interact with protein. Copyright © 2012 Elsevier B.V. All rights reserved.

Analyte Flux at a Biomaterial–Tissue Interface over Time: Implications for Sensors for Type 1 and 2 Diabetes Mellitus

PubMed Central

Ekberg, Neda Rajamand; Brismar, Kerstin; Malmstedt, Jonas; Hedblad, Mari-Anne; Adamson, Ulf; Ungerstedt, Urban; Wisniewski, Natalie

2010-01-01

Objective The very presence of an implanted sensor (a foreign body) causes changes in the adjacent tissue that may alter the analytes being sensed. The objective of this study was to investigate changes in glucose availability and local tissue metabolism at the sensor–tissue interface in patients with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). Method Microdialysis was used to model implanted sensors. Capillary glucose and subcutaneous (sc) microdialysate analytes were monitored in five T1DM and five T2DM patients. Analytes included glucose, glycolysis metabolites (lactate, pyruvate), a lipolysis metabolite (glycerol), and a protein degradation byproduct (urea). On eight consecutive days, four measurements were taken during a period of steady state blood glucose. Results Microdialysate glucose and microdialysate-to-blood-glucose ratio increased over the first several days in all patients. Although glucose recovery eventually stabilized, the lactate levels continued to rise. These trends were explained by local inflammatory and microvascular changes observed in histological analysis of biopsy samples. Urea concentrations mirrored glucose trends. Urea is neither produced nor consumed in sc tissue, and so the initially increasing urea trend is explained by increased local capillary presence during the inflammatory process. Pyruvate in T2DM microdialysate was significantly higher than in T1DM, an observation that is possibly explained by mitochondrial dysfunction in T2DM. Glycerol in T2DM microdialysate (but not in T1DM) was higher than in healthy volunteers, which is likely explained by sc insulin resistance (insulin is a potent antilipolytic hormone). Urea was also higher in microdialysate of patients with diabetes mellitus compared to healthy volunteers. Urea is a byproduct of protein degradation, which is known to be inhibited by insulin. Therefore, insulin deficiency or resistance may explain the higher urea levels. To our knowledge, this is the first histological evaluation of a human tissue biopsy containing an implanted glucose monitoring device. Conclusions Monitoring metabolic changes at a material–tissue interface combined with biopsy histology helped to formulate an understanding of physiological changes adjacent to implanted glucose sensors. Microdialysate glucose trends were similar over 1-week in T1DM and T2DM; however, differences in other analytes indicated wound healing and metabolic activities in the two patient groups differ. We propose explanations for the specific observed differences based on differential insulin insufficiency/resistance and mitochondrial dysfunction in T1DM versus T2DM. PMID:20920426

Analyte flux at a biomaterial-tissue interface over time: implications for sensors for type 1 and 2 diabetes mellitus.

PubMed

Ekberg, Neda Rajamand; Brismar, Kerstin; Malmstedt, Jonas; Hedblad, Mari-Anne; Adamson, Ulf; Ungerstedt, Urban; Wisniewski, Natalie

2010-09-01

The very presence of an implanted sensor (a foreign body) causes changes in the adjacent tissue that may alter the analytes being sensed. The objective of this study was to investigate changes in glucose availability and local tissue metabolism at the sensor-tissue interface in patients with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). Microdialysis was used to model implanted sensors. Capillary glucose and subcutaneous (sc) microdialysate analytes were monitored in five T1DM and five T2DM patients. Analytes included glucose, glycolysis metabolites (lactate, pyruvate), a lipolysis metabolite (glycerol), and a protein degradation byproduct (urea). On eight consecutive days, four measurements were taken during a period of steady state blood glucose. Microdialysate glucose and microdialysate-to-blood-glucose ratio increased over the first several days in all patients. Although glucose recovery eventually stabilized, the lactate levels continued to rise. These trends were explained by local inflammatory and microvascular changes observed in histological analysis of biopsy samples. Urea concentrations mirrored glucose trends. Urea is neither produced nor consumed in sc tissue, and so the initially increasing urea trend is explained by increased local capillary presence during the inflammatory process. Pyruvate in T2DM microdialysate was significantly higher than in T1DM, an observation that is possibly explained by mitochondrial dysfunction in T2DM. Glycerol in T2DM microdialysate (but not in T1DM) was higher than in healthy volunteers, which is likely explained by sc insulin resistance (insulin is a potent antilipolytic hormone). Urea was also higher in microdialysate of patients with diabetes mellitus compared to healthy volunteers. Urea is a byproduct of protein degradation, which is known to be inhibited by insulin. Therefore, insulin deficiency or resistance may explain the higher urea levels. To our knowledge, this is the first histological evaluation of a human tissue biopsy containing an implanted glucose monitoring device. Monitoring metabolic changes at a material-tissue interface combined with biopsy histology helped to formulate an understanding of physiological changes adjacent to implanted glucose sensors. Microdialysate glucose trends were similar over 1-week in T1DM and T2DM; however, differences in other analytes indicated wound healing and metabolic activities in the two patient groups differ. We propose explanations for the specific observed differences based on differential insulin insufficiency/resistance and mitochondrial dysfunction in T1DM versus T2DM. © 2010 Diabetes Technology Society.

Hepatic and extrahepatic distribution of ornithine urea cycle enzymes in holocephalan elephant fish (Callorhinchus milii).

PubMed

Takagi, Wataru; Kajimura, Makiko; Bell, Justin D; Toop, Tes; Donald, John A; Hyodo, Susumu

2012-04-01

Cartilaginous fish comprise two subclasses, the Holocephali (chimaeras) and Elasmobranchii (sharks, skates and rays). Little is known about osmoregulatory mechanisms in holocephalan fishes except that they conduct urea-based osmoregulation, as in elasmobranchs. In the present study, we examined the ornithine urea cycle (OUC) enzymes that play a role in urea biosynthesis in the holocephalan elephant fish, Callorhinchus milii (cm). We obtained a single mRNA encoding carbamoyl phosphate synthetase III (cmCPSIII) and ornithine transcarbamylase (cmOTC), and two mRNAs encoding glutamine synthetases (cmGSs) and two arginases (cmARGs), respectively. The two cmGSs were structurally and functionally separated into two types: brain/liver/kidney-type cmGS1 and muscle-type cmGS2. Furthermore, two alternatively spliced transcripts with different sizes were found for cmgs1 gene. The longer transcript has a putative mitochondrial targeting signal (MTS) and was predominantly expressed in the liver and kidney. MTS was not found in the short form of cmGS1 and cmGS2. A high mRNA expression and enzyme activities were found in the liver and muscle. Furthermore, in various tissues examined, mRNA levels of all the enzymes except cmCPSIII were significantly increased after hatching. The data show that the liver is the important organ for urea biosynthesis in elephant fish, but, extrahepatic tissues such as the kidney and muscle may also contribute to the urea production. In addition to the role of the extrahepatic tissues and nitrogen metabolism, the molecular and functional characteristics of multiple isoforms of GSs and ARGs are discussed. Copyright © 2011 Elsevier Inc. All rights reserved.

Teratology study of derivatives of tetramethylcyclopropyl amide analogues of valproic acid in mice.

PubMed

Okada, Akinobu; Onishi, Yuko; Aoki, Yoshinobu; Yagen, Boris; Sobol, Eyal; Bialer, Meir; Fujiwara, Michio

2006-06-01

Although valproic acid (VPA) is used extensively for treating various kinds of epilepsies, it is well known that it causes neural tube and skeletal defects in both humans and animals. The amide and urea derivatives of the tetramethylcylcopropyl VPA analogue, N-methoxy-2,2,3,3-tetramethylcyclopropanecarboxamide (N-methoxy-TMCD) and 2,2,3,3-tetramethylcyclopropanecarbonylurea (TMC-urea), were synthesized and shown to have a more potent anticonvulsant activity than VPA. The objective of this study was to investigate the teratogenic effects of these compounds in NMRI mice. Pregnant NMRI mice were given a single subcutaneous injection of either VPA, N-methoxy-TMCD, or TMC-urea at 1.8 and 3.6 mmol/kg on gestation day (GD) 8. Cesarean section was performed on GD 18. First, the live fetuses were examined to detect any external malformations, then their skeletons were double-stained for bone and cartilage and subsequently examined. Significant increases in fetal losses and neural tube defects were observed with administration of VPA at 3.6 mmol/kg when compared to the vehicle control. In contrast, upon cesarean section, there were no significant differences between either N-methoxy-TMCD or TMC-urea and the control groups for any parameter. Skeletal examination revealed that a number of the abnormalities were induced by VPA dose-dependently at high rates of incidence. These abnormalities were mainly at the axial skeletal level. However, lower frequencies of skeletal abnormality were observed with N-methoxy-TMCD and TMC-urea than with VPA. In addition to their more potent antiepileptic activity, these findings clearly indicate that N-methoxy-TMCD and TMC-urea are distinctly less teratogenic than VPA in NMRI mice.

Urinary levels of novel kidney biomarkers and risk of true worsening renal function and mortality in patients with acute heart failure.

PubMed

Sokolski, Mateusz; Zymliński, Robert; Biegus, Jan; Siwołowski, Paweł; Nawrocka-Millward, Sylwia; Todd, John; Yerramilli, Malli Rama; Estis, Joel; Jankowska, Ewa Anita; Banasiak, Waldemar; Ponikowski, Piotr

2017-06-01

Recent studies indicate the need to redefine worsening renal function (WRF) in acute heart failure (AHF), linking a rise in creatinine with clinical status to identify patients who develop 'true WRF'. We evaluated the usefulness of serial assessment of urinary levels of neutrophil gelatinase-associated lipocalin (uNGAL), kidney injury molecule-1 (uKIM-1), and cystatin C (uCysC) for prediction of 'true WRF'. In 132 patients with AHF, uNGAL, uKIM-1, and uCysC were measured using a highly sensitive immunoassay based on a single-molecule counting technology (Singulex, Alameda, CA, USA) at baseline, day 2, and day 3. Patients who developed WRF (a ≥0.3 mg/dL increase in serum creatinine or a >25% decrease in the estimated glomerular filtration rate from the baseline value) were differentiated into those 'true WRF' (presence of deterioration/no improvement in clinical status during hospitalization) vs. 'pseudo-WRF' (uneventful clinical course). 'True WRF' occurred in 13 (10%), 'pseudo-WRF' in 15 (11%), whereas the remaining 104 (79%) patients did not develop WRF. Patients with 'true WRF' were more often females, had higher levels of NT-proBNP, creatinine, and urea on admission, higher urine albumin to creatinine ratio at day 2, higher uNGAL at baseline, day 2, and day 3, and higher KIM-1 at day 2 (vs. pseudo-WRF vs. without WRF, all P < 0.05). Patients with pseudo-WRF did not differ from those without WRF. In the multivariable model, elevated uNGAL at all time points and uKIM-1 at day 2 remained independent predictors of 'true WRF'. Elevated levels of uNGAL and uKIM-1 may predict development of 'true WRF' in AHF. © 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology.

Role of Urea-Aromatic Stacking Interactions in Stabilizing the Aromatic Residues of the Protein in Urea-Induced Denatured State.

PubMed

Goyal, Siddharth; Chattopadhyay, Aditya; Kasavajhala, Koushik; Priyakumar, U Deva

2017-10-25

A delicate balance of different types of intramolecular interactions makes the folded states of proteins marginally more stable than the unfolded states. Experiments use thermal, chemical, or mechanical stress to perturb the folding equilibrium for examining protein stability and the protein folding process. Elucidation of the mechanism by which chemical denaturants unfold proteins is crucial; this study explores the nature of urea-aromatic interactions relevant in urea-assisted protein denaturation. Free energy profiles corresponding to the unfolding of Trp-cage miniprotein in the presence and absence of urea at three different temperatures demonstrate the distortion of the hydrophobic core to be a crucial step. Exposure of the Trp6 residue to the solvent is found to be favored in the presence of urea. Previous experiments showed that urea has a high affinity for aromatic groups of proteins. We show here that this is due to the remarkable ability of urea to form stacking and NH-π interactions with aromatic groups of proteins. Urea-nucleobase stacking interactions have been shown to be crucial in urea-assisted RNA unfolding. Examination of these interactions using microsecond-long unrestrained simulations shows that urea-aromatic stacking interactions are stabilizing and long lasting. Further MD simulations, thermodynamic integration, and quantum mechanical calculations on aromatic model systems reveal that such interactions are possible for all the aromatic amino acid side-chains. Finally, we validate the ubiquitous nature of urea-aromatic stacking interactions by analyzing experimental structures of urea transporters and proteins crystallized in the presence of urea or urea derivatives.

The Basic Metabolic Profile in Heart Failure-Marker and Modifier.

PubMed

Elfar, Ahmed; Sambandam, Kamalanathan K

2017-08-01

The physiologic determinants of each of the components of the basic metabolic profile in patients with heart failure will be explored. Additionally, the review will discuss the prognostic value of alterations in the basic metabolic profile as well as their effects on management. Abnormalities in the basic metabolic profile have significant correlation with clinical outcomes and can modify treatment in heart failure. Hypochloremia has recently received increased attention for these reasons. Elevated creatinine, increased blood urea nitrogen, hyponatremia, and hypochloremia correlate with worse mortality and diuretic resistance in heart failure. Hypokalemia, even when mild, has proven to be a worse clinical indicator than modest elevations in serum potassium. Hypochloremia is mechanistically linked to hyponatremia and metabolic alkalosis, but recent compelling data suggests that it can provide more discriminating prognostic information. Knowledge of the physiologic basis for each of these alterations informs their management.

The Processes of Scientific Discovery: The Strategy of Experimentation

DTIC Science & Technology

1987-09-29

RPT C3 : C U.SERS 22a NAME OF RESPONSIBLE INDIVIDUAL 22b TELEPHONE (include Area Code) 22C. OFFICR SYMBOL jr. Alan L. Mevrowitz (202) 696-430?2NOQ001...34omithine may donate an amino group to urea", (4) its description is given at the atomic level (Example: " C in urea comes from carbon-dioxide"). These...reactant, and there is a hypothesis that A produces C with B as an intermediate product, then carry out experiments on A and 8, and compare rates of

EFFECT OF ENDOSPERM HARDNESS ON AN ETHANOL PROCESS USING A GRANULAR STARCH HYDROLYZING ENZYME

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, P; W Liu, D B; Johnston, K D

Granular starch hydrolyzing enzymes (GSHE) can hydrolyze starch at low temperature (32°C). The dry grind process using GSHE (GSH process) has fewer unit operations and no changes in process conditions (pH 4.0 and 32°C) compared to the conventional process because it dispenses with the cooking and liquefaction step. In this study, the effects of endosperm hardness, protease, urea, and GSHE levels on GSH process were evaluated. Ground corn, soft endosperm, and hard endosperm were processed using two GSHE levels (0.1 and 0.4 mL per 100 g ground material) and four treatments of protease and urea addition. Soft and hard endospermmore » materials were obtained by grinding and sifting flaking grits from a dry milling pilot plant; classifications were confirmed using scanning electron microscopy. During 72 h of simultaneous granular starch hydrolysis and fermentation (GSHF), ethanol and glucose profiles were determined using HPLC. Soft endosperm resulted in higher final ethanol concentrations compared to ground corn or hard endosperm. Addition of urea increased final ethanol concentrations for soft and hard endosperm. Protease addition increased ethanol concentrations and fermentation rates for soft endosperm, hard endosperm, and ground corn. The effect of protease addition on ethanol concentrations and fermentation rates was most predominant for soft endosperm, less for hard endosperm, and least for ground corn. Samples (soft endosperm, hard endosperm, or corn) with protease resulted in higher (1.0% to 10.5% v/v) ethanol concentration compared to samples with urea. The GSH process with protease requires little or no urea addition. For fermentation of soft endosperm, GSHE dose can be reduced. Due to nutrients (lipids, minerals, and soluble proteins) present in corn that enhance yeast growth, ground corn fermented faster at the beginning than hard and soft endosperm.« less

Evaluation of nephroprotective activity of Musa paradisiaca L. in gentamicin-induced nephrotoxicity.

PubMed

Abbas, Khizar; Rizwani, Ghazala H; Zahid, Hina; Qadir, M Imran

2017-05-01

The objective of the study was to investigate the nephroprotective activity of methanolic extract of different morphological parts (bract, flower, trachea and tracheal fluid) of Musa paradisiaca L. (Family: Musaceae) against gentamicin-induced nephrotoxicity in mice. Gentamicin produced significant changes in biochemical (increased levels of blood urea nitrogen level, blood urea, and serum creatinine), and histological parameters in mice. Treatment with methanolic extract of bract (100 and 250mg/kg, b.w) and flowering stalk (trachea) (250 and 500mg/kg, b.w) significantly prevented biochemical and histological changes produced by gentamicin toxicity. The extracts of M. paradisiaca (bract and flowering stalk) could contribute a lead to discovery of a new drug for the treatment of drug-induced nephrotoxicity.

Urea immunoliposome inhibits human vascular endothelial cell proliferation for hemangioma treatment

PubMed Central

2013-01-01

Background Urea injection has been used in hemangioma treatment as sclerotherapy. It shrinks vascular endothelial cells and induces degeneration, necrosis, and fibrosis. However, this treatment still has disadvantages, such as lacking targeting and difficulty in controlling the urea dosage. Thus, we designed a urea immunoliposome to improve the efficiency of treatment. Methods The urea liposome was prepared by reverse phase evaporation. Furthermore, the urea immunoliposome was generated by coupling the urea liposome with a vascular endothelial growth factor receptor (VEGFR) monoclonal antibody using the glutaraldehyde cross-linking method. The influence of the urea immunoliposome on cultured human hemangioma vascular endothelial cells was observed preliminarily. Results Urea immunoliposomes showed typical liposome morphology under a transmission electron microscope, with an encapsulation percentage of 54.4% and a coupling rate of 36.84% for anti-VEGFR. Treatment with the urea immunoliposome significantly inhibited the proliferation of hemangioma vascular endothelial cells (HVECs) in a time- and dose-dependent manner. Conclusions The urea immunoliposome that we developed distinctly and persistently inhibited the proliferation of HVECs and is expected to be used in clinical hemangioma treatment. PMID:24266957

Dry skin (xerosis) in patients undergoing maintenance haemodialysis: the role of decreased sweating of the eccrine sweat gland.

PubMed

Park, T H; Park, C H; Ha, S K; Lee, S H; Song, K S; Lee, H Y; Han, D S

1995-12-01

The aetiology and the pathophysiological mechanisms underlying the development of dry skin in uraemia are still unclear, but the hydration status of stratum corneum clearly influences the appearance of skin. The xerotic skin texture is often referred to as 'dry skin' and has been suggested as a cause of uraemic pruritus. To understand the aetiology of dry skin in uraemia we measured the status of skin surface hydration of uraemic patients with the corneometer and skin surface hydrometer, the functional capacity and the urea concentration of stratum corneum and the response of eccrine sweat gland to sudorific agent (0.05% pilocarpine HCL) in 18 age-matched haemodialysis patients and 10 healthy volunteers. We also performed the water sorption-desorption test to uraemic and control subjects after application of urea in various concentrations. Uraemic patient's skin showed decreased water content compared to control subjects. However, we found no correlation between dry skin and pruritus. Although the urea concentration of the horny layer in uraemic patients was elevated compared to control subjects (28.2 microgram/cm2 vs 5.04 micrograms/cm2, P < 0.05), its moisturizing effect to relieve pruritus is questionable because its artificial application revealed no improvement of the functional capacity of horny layer in concentration 5 times higher than the physiological concentration. Uraemic patients showed decreased sweating response to sudorific agent. In conclusion, the functional abnormalities of eccrine sweat glands may be account for dry skin in uraemic patients at least in part, but there is no correlation between xerosis and pruritus.

Effect of Unripe Plantain (Musa paradisiaca) and Ginger (Zingiber officinale) on Renal Dysfunction in Streptozotocin-Induced Diabetic Rats.

PubMed

Iroaganachi, Mercy; Eleazu, Chinedum; Okafor, Polycarp

2015-03-20

Although unripe plantain (Musa paradisiaca) and ginger (Zingiber officinale) are used as single plants to manage diabetes mellitus in Nigeria, the possibility of combining them in a typical diabetic diet and the glycemic response elicited as a result of such combination has not been investigated. To determine the effect of unripe plantain and ginger on serum total proteins, albumin, creatinine and urea levels of streptozotocin induced diabetic rats. Twenty four male albino rats were used and were divided into 4 groups of 6 rats each. Group 1 (non-diabetic) received standard rat feeds; Group 2 (diabetic) received standard rat feeds; Group 3 received unripe plantain pellets and Group 4 received unripe plantain+ginger pellets. There were significant increases (P=0.045) of both serum urea and creatinine, but significant decreases (P=0.045) of both serum total protein and albumin levels, in Group 2 rats compared with Group 1. There were significant decreases (P=0.033) of both serum urea and creatinine levels of Group 3 and 4 rats compared with Group 2. In addition, there were significant increases of both serum total protein and albumin levels (P=0.033) in Group 3 rats compared with Group 2, but the comparison of serum total protein and albumin levels between Group 4 and Group 2 did not reach the significant level (P=0.056 and P=0.065 for serum total protein and albumin levels, respectively. Combination of unripe plantain and ginger at the ratio used in the management of renal dysfunction in diabetics was not very effective compared with unripe plantain alone.

Molecular insight into the counteraction of trehalose on urea-induced protein denaturation using molecular dynamics simulation.

PubMed

Zhang, Na; Liu, Fu-Feng; Dong, Xiao-Yan; Sun, Yan

2012-06-21

Considerable experimental evidence indicates that trehalose can counteract the denaturing effects of urea on proteins. However, its molecular mechanism remains unknown due to the limitations of current experimental techniques. Herein, molecular dynamics simulations were performed to investigate the counteracting effects of trehalose against urea-induced denaturation of chymotrypsin inhibitor 2. The simulations indicate that the protein unfolds in 8 mol/L urea, but at the same condition the protein retains its native structure in the ternary solution of 8 mol/L urea and 1 mol/L trehalose. It is confirmed that the preferential exclusion of trehalose from the protein surface is the origin of its counteracting effects. It is found that trehalose binds urea via hydrogen bonds, so urea molecules are also expelled from the protein surface along with the preferential exclusion of trehalose. The exclusion of urea from the protein surface leads to the alleviation of the Lennard-Jones interactions between urea and the hydrophobic side chains of the protein in the ternary solution. In contrast, the electrostatic interactions between urea and the protein change little in the presence of trehalose because the decrease in the electrostatic interactions between urea and the protein backbone is canceled by the increase in the electrostatic interactions between urea and the charged side chains of the protein. The results have provided molecular explanations for the counteraction of urea-induced protein denaturation by trehalose.

Expression of urea transporters and their regulation.

PubMed

Klein, Janet D

2014-01-01

UT-A and UT-B families of urea transporters consist of multiple isoforms that are subject to regulation of both acutely and by long-term measures. This chapter provides a brief overview of the expression of the urea transporter forms and their locations in the kidney. Rapid regulation of UT-A1 results from the combination of phosphorylation and membrane accumulation. Phosphorylation of UT-A1 has been linked to vasopressin and hyperosmolality, although through different kinases. Other acute influences on urea transporter activity are ubiquitination and glycosylation, both of which influence the membrane association of the urea transporter, again through different mechanisms. Long-term regulation of urea transport is most closely associated with the environment that the kidney experiences. Low-protein diets may influence the amount of urea transporter available. Conditions of osmotic diuresis, where urea concentrations are low, will prompt an increase in urea transporter abundance. Although adrenal steroids affect urea transporter abundance, conflicting reports make conclusions tenuous. Urea transporters are upregulated when P2Y2 purinergic receptors are decreased, suggesting a role for these receptors in UT regulation. Hypercalcemia and hypokalemia both cause urine concentration deficiencies. Urea transporter abundances are reduced in aging animals and animals with angiotensin-converting enzyme deficiencies. This chapter will provide information about both rapid and long-term regulation of urea transporters and provide an introduction into the literature.

Construction of a simple optical sensor based on air stable lipid film with incorporated urease for the rapid detection of urea in milk.

PubMed

Nikoleli, Georgia-Paraskevi; Nikolelis, Dimitrios P; Methenitis, Constantinos

2010-08-18

This work describes the construction of a simple optical sensor for the rapid, selective and sensitive detection of urea in milk using air stable lipid films with incorporated urease. The lipid film is stabilized on a glass filter by polymerization using UV (ultra-violet) radiation prior its use. Methacrylic acid was the functional monomer, ethylene glycol dimethacrylate was the crosslinker and 2,2'-azobis-(2-methylpropionitrile) was the initiator. Urease is incorporated within this mixture prior to the polymerization. The presence of the enzyme in these films quenched this fluorescence and the colour became similar to that of the filters without the lipid films. A drop of aqueous solution of urea provided a "switching on" of the fluorescence which allows the rapid detection of this compound at the levels of 10(-8) M concentrations. The investigation of the effect of potent interferences included a wide range of compounds usually found in foods and also of proteins and lipids. These lipid membranes were used for the rapid detection of urea in milk. Copyright 2010 Elsevier B.V. All rights reserved.

Bio-activity of aminosulfonyl ureas in the light of nucleic acid bases and DNA base pair interaction.

PubMed

Mondal Roy, Sutapa

2018-08-01

The quantum chemical descriptors based on density functional theory (DFT) are applied to predict the biological activity (log IC 50 ) of one class of acyl-CoA: cholesterol O-acyltransferase (ACAT) inhibitors, viz. aminosulfonyl ureas. ACAT are very effective agents for reduction of triglyceride and cholesterol levels in human body. Successful two parameter quantitative structure-activity relationship (QSAR) models are developed with a combination of relevant global and local DFT based descriptors for prediction of biological activity of aminosulfonyl ureas. The global descriptors, electron affinity of the ACAT inhibitors (EA) and/or charge transfer (ΔN) between inhibitors and model biosystems (NA bases and DNA base pairs) along with the local group atomic charge on sulfonyl moiety (∑Q Sul ) of the inhibitors reveals more than 90% efficacy of the selected descriptors for predicting the experimental log (IC 50 ) values. Copyright © 2018 Elsevier Ltd. All rights reserved.

Pyridylthiazole-based ureas as inhibitors of Rho associated protein kinases (ROCK1 and 2)†

PubMed Central

Pireddu, Roberta; Forinash, Kara D.; Sun, Nan N.; Martin, Mathew P.; Sung, Shen-Shu; Alexander, Brian; Zhu, Jin-Yi; Guida, Wayne C.; Schönbrunn, Ernst; Sebti, Saïd M.; Lawrence, Nicholas J.

2012-01-01

Potent ROCK inhibitors of a new class of 1-benzyl-3-(4-pyridylthiazol-2-yl)ureas have been identified. Remarkable differences in activity were observed for ureas bearing a benzylic stereogenic center. Derivatives with hydroxy, methoxy and amino groups at the meta position of the phenyl ring give rise to the most potent inhibitors (low nM). Substitutions at the para position result in substantial loss of potency. Changes at the benzylic position are tolerated resulting in significant potency in the case of methyl and methylenehydroxy groups. X-Ray crystallography was used to establish the binding mode of this class of inhibitors and provides an explanation for the observed differences of the enantiomer series. Potent inhibition of ROCK in human lung cancer cells was shown by suppression of the levels of phosphorylation of the ROCK substrate MYPT-1. PMID:23275831

In vivo urea cycle flux distinguishes and correlates with phenotypic severity in disorders of the urea cycle

PubMed Central

Lee, Brendan; Yu, Hong; Jahoor, Farook; O'Brien, William; Beaudet, Arthur L.; Reeds, Peter

2000-01-01

Urea cycle disorders are a group of inborn errors of hepatic metabolism that result in often life-threatening hyperammonemia and hyperglutaminemia. Clinical and laboratory diagnosis of partial deficiencies during asymptomatic periods is difficult, and correlation of phenotypic severity with either genotype and/or in vitro enzyme activity is often imprecise. We hypothesized that stable isotopically determined in vivo rates of total body urea synthesis and urea cycle-specific nitrogen flux would correlate with both phenotypic severity and carrier status in patients with a variety of different enzymatic deficiencies of the urea cycle. We studied control subjects, patients, and their relatives with different enzymatic deficiencies affecting the urea cycle while consuming a low protein diet. On a separate occasion the subjects either received a higher protein intake or were treated with an alternative route medication sodium phenylacetate/benzoate (Ucephan), or oral arginine supplementation. Total urea synthesis from all nitrogen sources was determined from [18O]urea labeling, and the utilization of peripheral nitrogen was estimated from the relative isotopic enrichments of [15N]urea and [15N]glutamine during i.v. co-infusions of [5-(amide)15N]glutamine and [18O]urea. The ratio of the isotopic enrichments of 15N-urea/15N-glutamine distinguished normal control subjects (ratio = 0.42 ± 0.06) from urea cycle patients with late (0.17 ± 0.03) and neonatal (0.003 ± 0.007) presentations irrespective of enzymatic deficiency. This index of urea cycle activity also distinguished asymptomatic heterozygous carriers of argininosuccinate synthetase deficiency (0.22 ± 0.03), argininosuccinate lyase deficiency (0.35 ± 0.11), and partial ornithine transcarbamylase deficiency (0.26 ± 0.06) from normal controls. Administration of Ucephan lowered, and arginine increased, urea synthesis to the degree predicted from their respective rates of metabolism. The 15N-urea/15N-glutamine ratio is a sensitive index of in vivo urea cycle activity and correlates with clinical severity. Urea synthesis is altered by alternative route medications and arginine supplementation to the degree that is to be expected from theory. This stable isotope protocol provides a sensitive tool for evaluating the efficacy of therapeutic modalities and acts as an aid to the diagnosis and management of urea cycle patients. PMID:10869432

Assessment of Early Postpartum Reproductive Performance in Two High Producing Estonian Dairy Herds

PubMed Central

Kask, K; Kurykin, J; Lindjärv, R; Kask, A; Kindahl, H

2003-01-01

Early postpartum (6 weeks) ovarian activity, hormonal profiles, uterine involution, uterine infections, serum electrolytes, glucose, milk acetoacetate and blood urea nitrogen (BUN) levels were studied in 2 Estonian high producing dairy herd with annual milk production of 7688 (Farm A) and 9425 (Farm B). From each farm 10 cows, with normal calving performance were used. Blood samples for the hormonal (PGF2α-metabolite, progesterone) analyses were withdrawn. On day 25 PP blood serum samples were taken for the evaluation of metabolic/electrolyte status. On the same day estimation of milk acetoacetate values was done. The ultrasound (US) was started on day 7 PP and was performed every 3rd day until the end of experiment. Uterine content, follicular activity and sizes of the largest follicle and corpus luteum were monitored and measured. Vaginal discharge and uterine tone were recorded during the rectal palpation. Each animal in the study was sampled for bacteriological examination using endometrial biopsies once a week. Two types of PGF2α-metabolite patterns were detected: elevated levels during 14 days PP, then decline to the basal level and then a second small elevation at the time of final elimination of the bacteria from the uterus; or elevated levels during first 7 days PP, then decline to the basal level and a second small elevation before the final elimination of bacteria. Endometritis was diagnosed in 5 cows in farm A and in 3 cows in farm B respectively. In farm A, 5 cows out of 10 ovulated during experimental period and in 1 cow cystic ovaries were found. In farm B, 3 cows out of 10 ovulated. In 3 cows cystic ovaries were found. Altogether 40% of cows had their first ovulation during the experimental period. Three cows in farm A and 5 cows in farm B were totally bacteria negative during the experimental period. The most frequent bacteria found were A. pyogenes, Streptococcus spp., E. coli., F. necrophorum and Bacteroides spp. The highest incidence of bacteriological species was found during the first 3 weeks in both farms. All animals were free from bacteria after 5th week PP in farm A and after 4th week in farm B respectively. Serum electrolytes and glucose levels were found to be within the reference limits for the cows in both farms. No significant difference was found between farms (p > 0.05). Low phosphorus levels were found in both farms. Significant difference (p < 0.05) was found in BUN levels between farms. In both farms milk acetoacetate values were staying within the reference range given for the used test (<100 μmol/l). The uterine involution and bacterial elimination in the investigated cows could consider as normal but more profound metabolic studies could be needed to find reasons for later resumption of ovarian activity. Some recommendations to changing feeding regimes and strategies should also be given. PMID:15074626

Role of protein kinase C-α in hypertonicity-stimulated urea permeability in mouse inner medullary collecting ducts.

PubMed

Wang, Yanhua; Klein, Janet D; Froehlich, Otto; Sands, Jeff M

2013-01-15

The kidney's ability to concentrate urine is vitally important to our quality of life. In the hypertonic environment of the kidney, urea transporters must be regulated to optimize function. We previously showed that hypertonicity increases urea permeability and that the protein kinase C (PKC) blockers chelerythrine and rottlerin decreased hypertonicity-stimulated urea permeability in rat inner medullary collecting ducts (IMCDs). Because PKCα knockout (PKCα(-/-)) mice have a urine-concentrating defect, we tested the effect of hypertonicity on urea permeability in isolated perfused mouse IMCDs. Increasing the osmolality of perfusate and bath from 290 to 690 mosmol/kgH(2)O did not change urea permeability in PKCα(-/-) mice but significantly increased urea permeability in wild-type mice. To determine whether the response to protein kinase A was also missing in IMCDs of PKCα(-/-) mice, tubules were treated with vasopressin and subsequently with the PKC stimulator phorbol dibutyrate (PDBu). Vasopressin stimulated urea permeability in PKCα(-/-) mice. Like vasopressin, forskolin stimulated urea permeability in PKCα(-/-) mice. We previously showed that, in rats, vasopressin and PDBu have additive stimulatory effects on urea permeability. In contrast, in PKCα(-/-) mice, PDBu did not further increase vasopressin-stimulated urea permeability. Western blot analysis showed that expression of the UT-A1 urea transporter in IMCDs was increased in response to vasopressin in wild-type mice as well as PKCα(-/-) mice. Hypertonicity increased UT-A1 phosphorylation in wild-type mice but not in PKCα(-/-) mice. We conclude that PKCα mediates hypertonicity-stimulated urea transport but is not necessary for vasopressin stimulation of urea permeability in mouse IMCDs.

Effect of lycopene against cisplatin-induced acute renal injury in rats: organic anion and cation transporters evaluation.

PubMed

Erman, Fazilet; Tuzcu, Mehmet; Orhan, Cemal; Sahin, Nurhan; Sahin, Kazim

2014-04-01

In the present study, we investigated the effects of lycopene on the expression of organic anion transporters (OATs), organic cation transporters (OCTs), and multidrug resistance-associated proteins (MRPs) of cisplatin-induced nephrotoxicity in rats. Twenty-eight 8-week-old Wistar rats were divided into four groups: control, lycopene-treated (6 mg/kg BW by oral gavage), cisplatin-treated (7 mg/kg BW, IP), and lycopene in combination with cisplatin-treated groups. In the presence of cisplatin, serum urea nitrogen (urea-N) (48.5 vs. 124.3 mg/dl) and creatinine (0.29 vs. 1.37 mg/dl) levels and the kidney efflux transporters MRP2 and MRP4 levels were significantly increased, whereas OAT1, OAT3, OCT1, and OCT2 levels in kidney were decreased in the treated rats compared with normal control rats. However, administration of lycopene in combination with cisplatin resulted in a reduction in the serum urea-N (124.3 vs. 62.4) and creatinine (1.37 vs. 0.40) levels and the kidney efflux transporters MRP2 and MRP4 proteins in the kidneys. Administration of lycopene to acute renal injury-induced rats largely upregulated the organic anion transporters (OAT1 and 3) and organic cation transporters (OCT1 and 2) to decrease the side effects of cisplatin. The present study suggests that lycopene synergizes with its nephroprotective effect against cisplatin-induced acute kidney injury in rats.

Estimation of daily protein intake based on spot urine urea nitrogen concentration in chronic kidney disease patients.

PubMed

Kanno, Hiroko; Kanda, Eiichiro; Sato, Asako; Sakamoto, Kaori; Kanno, Yoshihiko

2016-04-01

Determination of daily protein intake in the management of chronic kidney disease (CKD) requires precision. Inaccuracies in recording dietary intake occur, and estimation from total urea excretion presents hurdles owing to the difficulty of collecting whole urine for 24 h. Spot urine has been used for measuring daily sodium intake and urinary protein excretion. In this cross-sectional study, we investigated whether urea nitrogen (UN) concentration in spot urine can be used to predict daily protein intake instead of the 24-h urine collection in 193 Japanese CKD patients (Stages G1-G5). After patient randomization into 2 datasets for the development and validation of models, bootstrapping was used to develop protein intake estimation models. The parameters for the candidate multivariate regression models were male gender, age, body mass index (BMI), diabetes mellitus, dyslipidemia, proteinuria, estimated glomerular filtration rate, serum albumin level, spot urinary UN and creatinine level, and spot urinary UN/creatinine levels. The final model contained BMI and spot urinary UN level. The final model was selected because of the higher correlation between the predicted and measured protein intakes r = 0.558 (95 % confidence interval 0.400, 0.683), and the smaller distribution of the difference between the measured and predicted protein intakes than those of the other models. The results suggest that UN concentration in spot urine may be used to estimate daily protein intake and that a prediction formula would be useful for nutritional control in CKD patients.

Modulation of cadmium-induced phytotoxicity in Cabomba caroliniana by urea involves photosynthetic metabolism and antioxidant status.

PubMed

Huang, Wenmin; Shao, Hui; Zhou, Sining; Zhou, Qin; Li, Wei; Xing, Wei

2017-10-01

Urea is a widespread organic pollutant, which can be a nitrogen source, playing different roles in the growth of submerged macrophytes depending on concentrations, while high cadmium (Cd) concentrations are often toxic to macrophytes. In order to evaluate the combined effect of urea and Cd on a submerged macrophyte, Cabomba caroliniana, the morphological and physiological responses of C. caroliniana in the presence of urea and Cd were studied. The results showed that high concentrations of urea (400mgL -1 ) and Cd (500µmolL -1 ) had negative effects on C. caroliniana. There were strong visible symptoms of toxicity after 4 days of exposure under Cd-alone, 400mgL -1 urea, and Cd+400mgL -1 urea treatments. In addition, 400mgL -1 urea and Cd had adverse effects on C. caroliniana's pigment system. Significant losses in chlorophyll fluorescence and photosynthetic rates, as well as Rubisco activity were also observed under Cd-alone, 400mgL -1 urea, and Cd+400mgL -1 urea treatments. 400mgL -1 urea markedly enhanced Cd toxicity in C. caroliniana, reflected by a sharp decrease in photosynthetic activity and more visible toxicity symptoms. The results of thiobarbituric acid reactive substances (TBARS) pointed to extreme oxidative stress in C. caroliniana induced under Cd or 400mgL -1 urea exposure. Exogenous ascorbate (AsA) protected C. caroliniana from adverse damage in 400mgL -1 urea, which further corroborated the oxidative stress claim under 400mgL -1 urea. However, results also demonstrated that lower urea concentration (10mgL -1 ) alleviated Cd-induced phytotoxicity by stimulating chlorophyll synthesis and photosynthetic activity, as well as activating the activity of catalase (CAT) and glutathione-S-transferase (GST), which may explain the alleviating effect of urea on C. caroliniana under Cd stress. Copyright © 2017 Elsevier Inc. All rights reserved.

Ammonia excretion and urea handling by fish gills: present understanding and future research challenges.

PubMed

Wilkie, Michael Patrick

2002-08-01

In fresh water fishes, ammonia is excreted across the branchial epithelium via passive NH(3) diffusion. This NH(3) is subsequently trapped as NH(4)(+) in an acidic unstirred boundary layer lying next to the gill, which maintains the blood-to-gill water NH(3) partial pressure gradient. Whole animal, in situ, ultrastructural and molecular approaches suggest that boundary layer acidification results from the hydration of CO(2) in the expired gill water, and to a lesser extent H(+) excretion mediated by apical H(+)-ATPases. Boundary layer acidification is insignificant in highly buffered sea water, where ammonia excretion proceeds via NH(3) diffusion, as well as passive NH(4)(+) diffusion due to the greater ionic permeability of marine fish gills. Although Na(+)/H(+) exchangers (NHE) have been isolated in marine fish gills, possible Na(+)/NH(4)(+) exchange via these proteins awaits evaluation using modern electrophysiological and molecular techniques. Although urea excretion (J(Urea)) was thought to be via passive diffusion, it is now clear that branchial urea handling requires specialized urea transporters. Four urea transporters have been cloned in fishes, including the shark kidney urea transporter (shUT), which is a facilitated urea transporter similar to the mammalian renal UT-A2 transporter. Another urea transporter, characterized but not yet cloned, is the basolateral, Na(+) dependent urea antiporter of the dogfish gill, which is essential for urea retention in ureosmotic elasmobranchs. In ureotelic teleosts such as the Lake Magadi tilapia and the gulf toadfish, the cloned mtUT and tUT are facilitated urea transporters involved in J(Urea). A basolateral urea transporter recently cloned from the gill of the Japanese eel (eUT) may actually be important for urea retention during salt water acclimation. A multi-faceted approach, incorporating whole animal, histological, biochemical, pharmacological, and molecular techniques is required to learn more about the location, mechanism of action, and functional significance of urea transporters in fishes. Copyright 2002 Wiley-Liss, Inc.

Distribution of creatinine following intravenous and oral administration to rats.

PubMed

Watanabe, J; Hirate, J; Iwamoto, K; Ozeki, S

1981-05-01

To evaluate the distribution of creatinine in rats, urinary, fecal and expiratory excretion, plasma levels and whole-body autoradiography following intravenous or oral administration of [carbonyl-14C]creatinine was investigated. More than 90% of the exogeneous creatinine was excreted in the urine in 24 hr following intravenous administration, and both fecal and expiratory excretion were only about 1%. In case of oral administration, however, it was found that expiratory excretion could not be neglected, ranging from about 1 to 30%. Plasma creatinine concentration-time curves following the intravenous administration (70.4 micrograms/kg or 400 mg/kg as creatinine) were analyzed according to a two-compartment open model. There were significant but very small differences in the pharmacokinetic parameters for these two doses. When these parameters were compared with those of urea, k12 and k21, which are transfer rate constants between compartment 1 and 2, for creatinine were significantly smaller than those of urea. On the other hand, k10 was larger in creatinine. Furthermore, (V'd)extrap for creatinine was about three times that of urea. Whole-body autoradiograms at 5 minutes following intravenous administration showed that exogeneous creatinine distributes with higher concentrations in liver, lung and kidney than in muscle and fat. This results was remarkably different from that of urea which distributes almost uniformly throughout the body at the same time. This difference observed in the autoradiograms would be the consequence of the fact that urea has larger k12 and k21 than creatinine.

High Protein Diet and Huntington's Disease

PubMed Central

Wu, Yih-Ru; Chen, Pei; Tsai, Fuu-Jen; Yang, Chueh-Lien; Tsao, Ya-Tzu; Chang, Wen; Hsieh, I-Shan; Chern, Yijuang; Soong, Bing-Wen

2015-01-01

Huntington’s disease (HD) is a neurodegenerative disorder caused by the huntingtin (HTT) gene with expanded CAG repeats. In addition to the apparent brain abnormalities, impairments also occur in peripheral tissues. We previously reported that mutant Huntingtin (mHTT) exists in the liver and causes urea cycle deficiency. A low protein diet (17%) restores urea cycle activity and ameliorates symptoms in HD model mice. It remains unknown whether the dietary protein content should be monitored closely in HD patients because the normal protein consumption is lower in humans (~15% of total calories) than in mice (~22%). We assessed whether dietary protein content affects the urea cycle in HD patients. Thirty HD patients were hospitalized and received a standard protein diet (13.7% protein) for 5 days, followed by a high protein diet (HPD, 26.3% protein) for another 5 days. Urea cycle deficiency was monitored by the blood levels of citrulline and ammonia. HD progression was determined by the Unified Huntington’s Disease Rating Scale (UHDRS). The HPD increased blood citrulline concentration from 15.19 μmol/l to 16.30 μmol/l (p = 0.0378) in HD patients but did not change blood ammonia concentration. A 2-year pilot study of 14 HD patients found no significant correlation between blood citrulline concentration and HD progression. Our results indicated a short period of the HPD did not markedly compromise urea cycle function. Blood citrulline concentration is not a reliable biomarker of HD progression. PMID:25992839

Thienoquinolins exert diuresis by strongly inhibiting UT-A urea transporters

PubMed Central

Ren, Huiwen; Wang, Yanhua; Xing, Yongning; Ran, Jianhua; Liu, Ming; Lei, Tianluo; Zhou, Hong; Li, Runtao; Sands, Jeff M.

2014-01-01

Urea transporters (UT) play an important role in the urine concentration mechanism by mediating intrarenal urea recycling, suggesting that UT inhibitors could have therapeutic use as a novel class of diuretic. Recently, we found a thienoquinolin UT inhibitor, PU-14, that exhibited diuretic activity. The purpose of this study was to identify more potent UT inhibitors that strongly inhibit UT-A isoforms in the inner medullary collecting duct (IMCD). Efficient thienoquinolin UT inhibitors were identified by structure-activity relationship analysis. Urea transport inhibition activity was assayed in perfused rat terminal IMCDs. Diuretic activity of the compound was determined in rats and mice using metabolic cages. The results show that the compound PU-48 exhibited potent UT-A inhibition activity. The inhibition was 69.5% with an IC50 of 0.32 μM. PU-48 significantly inhibited urea transport in perfused rat terminal IMCDs. PU-48 caused significant diuresis in UT-B null mice, which indicates that UT-A is the target of PU-48. The diuresis caused by PU-48 did not change blood Na+, K+, or Cl− levels or nonurea solute excretion in rats and mice. No toxicity was detected in cells or animals treated with PU-48. The results indicate that thienoquinolin UT inhibitors induce a diuresis by inhibiting UT-A in the IMCD. This suggests that they may have the potential to be developed as a novel class of diuretics with fewer side effects than classical diuretics. PMID:25298523

Thienoquinolins exert diuresis by strongly inhibiting UT-A urea transporters.

PubMed

Ren, Huiwen; Wang, Yanhua; Xing, Yongning; Ran, Jianhua; Liu, Ming; Lei, Tianluo; Zhou, Hong; Li, Runtao; Sands, Jeff M; Yang, Baoxue

2014-12-15

Urea transporters (UT) play an important role in the urine concentration mechanism by mediating intrarenal urea recycling, suggesting that UT inhibitors could have therapeutic use as a novel class of diuretic. Recently, we found a thienoquinolin UT inhibitor, PU-14, that exhibited diuretic activity. The purpose of this study was to identify more potent UT inhibitors that strongly inhibit UT-A isoforms in the inner medullary collecting duct (IMCD). Efficient thienoquinolin UT inhibitors were identified by structure-activity relationship analysis. Urea transport inhibition activity was assayed in perfused rat terminal IMCDs. Diuretic activity of the compound was determined in rats and mice using metabolic cages. The results show that the compound PU-48 exhibited potent UT-A inhibition activity. The inhibition was 69.5% with an IC50 of 0.32 μM. PU-48 significantly inhibited urea transport in perfused rat terminal IMCDs. PU-48 caused significant diuresis in UT-B null mice, which indicates that UT-A is the target of PU-48. The diuresis caused by PU-48 did not change blood Na(+), K(+), or Cl(-) levels or nonurea solute excretion in rats and mice. No toxicity was detected in cells or animals treated with PU-48. The results indicate that thienoquinolin UT inhibitors induce a diuresis by inhibiting UT-A in the IMCD. This suggests that they may have the potential to be developed as a novel class of diuretics with fewer side effects than classical diuretics. Copyright © 2014 the American Physiological Society.

Protective role of silymarin in a mouse model of renal Ischemia-Reperfusion injury.

PubMed

Tan, Jian; Hu, Jianpeng; He, Yonghui; Cui, Feilun

2015-10-31

We investigated the mechanism of action of silymarin in a mouse model of renal ischemia-reperfusion injury (I/R) to ascertain its role in the treatment of I/R injury. Twenty-four C57BL/6 male mice were divided randomly into three groups: control (sham); ischemia-reperfusion (I/R); silymarin + ischemia-reperfusion (silymarin + I/R). In sham mice, an abdominal incision was made, followed by dissection of the bilateral renal pedicle, with no further cross-clamping of arteries. Silymarin + I/R mice were administered 100 mg/kg silymarin daily for 7 consecutive days before surgery, whereas I/R mice were administered (i.g.) 0.9 % saline + 0.1 % (v/v) ethanol daily for 7 consecutive days before surgery. Silymarin + I/R and I/R mice were subjected to renal ischemia to induce acute kidney injury after 45-min clamping of bilateral renal arteries. Serum levels of creatinine and blood urea nitrogen levels were measured. Periodic acid-Schiff (PAS) staining was undertaken to detect damaged renal tissue. Myeloperoxidase (MPO) activity and immunofluorescent detection of CD68 expression was undertaken for each group. Levels of inflammatory cytokines secreted by renal tissue were monitored by ELISA. Apoptosis was detected by TUNEL staining. Expression of cleaved-caspase-3, Bcl-2 and Bax was detected by western blotting. Serum creatinine and blood urea nitrogen levels were elevated in silymarin + I/R and I/R groups compared with sham mice (p < 0.05), whereas those in the I/R group were significantly higher than in the silymarin + I/R group (p < 0.05). Number of damaged renal tubule cells and apoptotic cells in sham and silymarin + I/R groups was significantly lower than in I/R mice. MPO activity and secretion of inflammatory cytokines in silymarin + I/R and I/R groups was reduced (p < 0.05), and CD68 expression in silymarin + I/R mice was lower than in I/R mice (p < 0.05). Expression of cleaved-caspase-3 and Bax in the I/R group was significantly higher than in sham mice, whereas Bcl-2 expression was lower than in silymarin + I/R mice (p < 0.05). Silymarin can inhibit renal I/R injury by inhibiting release of inflammatory factors and regulating apoptosis.

Clinical outcomes of neonatal onset proximal versus distal urea cycle disorders do not differ.

PubMed

Ah Mew, Nicholas; Krivitzky, Lauren; McCarter, Robert; Batshaw, Mark; Tuchman, Mendel

2013-02-01

To compare the clinical course and outcome of patients diagnosed with one of 4 neonatal-onset urea cycle disorders (UCDs): deficiency of carbamyl phosphate synthase 1 (CPSD), ornithine transcarbamylase (OTCD), argininosuccinate synthase (ASD), or argininosuccinate lyase (ALD). Clinical, biochemical, and neuropsychological data from 103 subjects with neonatal-onset UCDs were derived from the Longitudinal Study of Urea Cycle Disorders, an observational protocol of the Urea Cycle Disorders Consortium, one of the Rare Disease Clinical Research Networks. Some 88% of the subjects presented clinically by age 7 days. Peak ammonia level was 963 μM in patients with proximal UCDs (CPSD or OTCD), compared with 589 μM in ASD and 573 μM in ALD. Roughly 25% of subjects with CPSD or OTCD, 18% of those with ASD, and 67% of those with ALD had a "honeymoon period," defined as the time interval from discharge from initial admission to subsequent admission for hyperammonemia, greater than 1 year. The proportion of patients with a poor outcome (IQ/Developmental Quotient <70) was greatest in ALD (68%), followed by ASD (54%) and CPSD/OTCD (47%). This trend was not significant, but was observed in both patients aged <4 years and those aged ≥ 4 years. Poor cognitive outcome was not correlated with peak ammonia level or duration of initial admission. Neurocognitive outcomes do not differ between patients with proximal UCDs and those with distal UCDs. Factors other than hyperammonemia may contribute to poor neurocognitive outcome in the distal UCDs. Copyright © 2013 Mosby, Inc. All rights reserved.

Assessment of Health Effects of Exogenous Urea: Summary and Key Findings.

PubMed

Dickerson, Aisha S; Lee, Janice S; Keshava, Channa; Hotchkiss, Andrew; Persad, Amanda S

2018-05-01

Urea has been utilized as a reductant in diesel fuels to lower emission of nitrogen oxides, igniting interest in probable human health hazards associated with exposure to exogenous urea. Here, we summarize and update key findings on potential health effects of exogenous urea, including carcinogenicity. No definitive target organs for oral exposure were identified; however, results in animal studies suggest that the liver and kidney could be potential target organs of urea toxicity. The available human-subject literature suggests that the impact on lung function is minimal. Based on the literature on exogenous urea, we concluded that there was inadequate information to assess the carcinogenic potential of urea, or perform a quantitative assessment to derive reference values. Given the limited information on exogenous urea, additional research to address gaps for exogenous urea should include long-term cancer bioassays, two-generation reproductive toxicity studies, and mode-of-action investigations.

Sulfonamide antibiotic removal and nitrogen recovery from synthetic urine by the combination of rotating advanced oxidation contactor and methylene urea synthesis process.

PubMed

Fukahori, S; Fujiwara, T; Ito, R; Funamizu, N

2015-01-01

The combination of nitrogen recovery and pharmaceutical removal processes for livestock urine treatment were investigated to suppress the discharge of pollutants and recover nitrogen as resources. We combined methylene urea synthesis from urea and adsorption and photocatalytic decomposition of sulfonamide antibiotic using rotating advanced oxidation contactor (RAOC) contained for obtaining both safe fertilizer and reclaimed water. The methylene urea synthesis could recover urea in synthetic urine, however, almost all sulfonamide antibiotic was also incorporated, which is unfavorable from a safety aspect if the methylene urea is to be used as fertilizer. Conversely, RAOC could remove sulfonamide antibiotic without consuming urea. It was also confirmed that the methylene urea could be synthesized from synthetic urine treated by RAOC. Thus, we concluded that RAOC should be inserted prior to the nitrogen recovery process for effective treatment of urine and safe use of methylene urea as fertilizer.

Synergistic behavior of glycine betaine-urea mixture: A molecular dynamics study

NASA Astrophysics Data System (ADS)

Kumar, Narendra; Kishore, Nand

2013-09-01

Glycine betaine (GB) is one of the most important osmolyte which is known to stabilize proteins as well as counteract the denaturing effect of urea. There have been many studies indicating protein stabilization and counteraction of the effect of urea by GB. However, the exact mechanism of counteraction is still debated and is of important research interest. In this study, distribution functions, hydrogen bonds, and energetics were analysed to understand different interactions between GB and urea, and their solvation properties in presence of each other. The results show that in the GB-urea mixture, GB acted as a stronger osmolyte and urea became a weaker denaturing agent than its individual counterparts. The increase in the solvation of urea and GB in GB-urea mixture and their mutual interactions through hydrogen bonding and coulombic energy resulted in more involvement of GB and urea with solvent as well as with themselves. This might result in the increase of the exclusion of GB from protein surface and decrease in the protein-urea interactions in the mixture. This synergistic behavior might be the prime reason for the counteraction of denaturing effect of urea by GB.

Mechanistic insights into osmolyte action in protein stabilization under harsh conditions: N-methylacetamide in glycine betaine-urea mixture

NASA Astrophysics Data System (ADS)

Kumar, Narendra; Kishore, Nand

2014-10-01

Glycine betaine (GB), a small naturally occurring osmolyte, stabilizes proteins and counteracts harsh denaturing conditions such as extremes of temperature, cellular dehydration, and presence of high concentration of urea. In spite of several studies on understanding mechanism of protein stabilization and counteraction of these harsh conditions by osmolytes, studies centred on GB, one of the most important osmolyte, are scarce, hence, there is need for more investigations. To explore mechanism of protein stabilization and counteraction of denaturing property of urea by GB, molecular dynamics studies of N-methylacetamide (NMA), a model peptide representing denatured state of a protein, in the presence of GB, urea, and GB-urea mixture were carried out. The results show that GB and urea work such that the strength of GB as a protecting osmolyte is increased and the denaturing ability of urea is decreased in the GB-urea mixture. It can be inferred that GB counteracts urea by decreasing its hydrophobic interactions with proteins. The mutual interactions between GB and urea also play an important role in protein stabilization. This study provides insights on osmolyte induced counteraction of denaturing property of urea.

Carcinogenic Activities and Sperm Abnormalities of Methicillin Resistance Staphylococcus aureus and Inhibition of Their Virulence Potentials by Ayamycin.

PubMed

El-Gendy, Mervat Morsy Abbas Ahmed; Abdel-Wahhab, Khaled G; Mannaa, Fathia A; Farghaly, Ayman A; El-Bondkly, Ahmed M A

2017-11-01

This investigation aimed to study the in vivo harmful effects of the subcutaneous injection of different methicillin resistance Staphylococcus aureus extracts (MRSA2, MRSA4, MRSA10, MRSA69, MRSA70, MRSA76, and MRSA78). Such strains represented the highest minimum inhibition concentration toward methicillin with various multidrug-resistant patterns. The obtained results revealed that rats injected with the MRSA4 extract died immediately after the last dose indicating the high cytotoxicity of MRSA4 strain (100% mortality). While the mortalities in other groups injected by the other MRSA extracts ranged from 50 to 75%. In comparison with the normal animal group, all MRSA extracts induced a hepatotoxic effect which was indicated from the significant (p < 0.01) increases in the activities of the serum alanine aminotransferase (ALAT) and aspartate aminotransferase (ASAT) enzymes. Moreover, alkaline phosphatase (ALP) combined with a partial nephrotoxicity that was monitored from the significant elevation of serum urea concentration. While serum creatinine levels did not affect. Similarly, a significant elevation was recorded in serum levels of tumor biomarkers (alpha fetoprotein; AFP, carcinoembryonic antigen; CEA, and lactate dehydrogenase; LDH) reflecting their carcinogenic potential. On the other hand, the percentage of micronuclei (MN) in polychromatic erythrocytes from bone marrow cells was statistically significant in all groups as compared to the control group. The percentage of sperm abnormalities was statistically significant compared to the control. Different types of head abnormalities and coiled tail were recorded. Consequently, the current study focused on fighting MRSA virulence factors by the new compound ayamycin, which proved to be potent anti-virulence factor against all MRSA strains under study by significant decreasing of their streptokinase activities, hemolysin synthesis, biofilm formation, and their cell surface hydrophobicity.

Role of ambient ammonia in particulate ammonium formation at a rural site in the North China Plain

NASA Astrophysics Data System (ADS)

Meng, Zhaoyang; Xu, Xiaobin; Lin, Weili; Ge, Baozhu; Xie, Yulin; Song, Bo; Jia, Shihui; Zhang, Rui; Peng, Wei; Wang, Ying; Cheng, Hongbing; Yang, Wen; Zhao, Huarong

2018-01-01

The real-time measurements of NH3 and trace gases were conducted, in conjunction with semi-continuous measurements of water-soluble ions in PM2.5 at a rural site in the North China Plain (NCP) from May to September 2013 in order to better understand chemical characteristics of ammonia and the impact of secondary ammonium aerosols on formation in the NCP. Extremely high NH3 and NH4+ concentrations were observed after a precipitation event within 7-10 days following urea application. Elevated NH3 levels coincided with elevated NH4+, indicating that NH3 likely influenced particulate ammonium mass. For the sampling period, the average conversion / oxidation ratios for NH4+ (NHR), SO42- (SOR), and NO3- (NOR) were estimated to be 0.30, 0.64, and 0.24, respectively. The increased NH3 concentrations, mainly from agricultural activities and regional transport, coincided with the prevailing meteorological conditions. The high NH3 level with NHR of about 0.30 indicates that the emission of NH3 in the NCP is much higher than needed for aerosol acid neutralisation, and NH3 plays an important role in the formation of secondary aerosols as a key neutraliser. The hourly data obtained were used to investigate gas-aerosol partitioning characteristics using the thermodynamic equilibrium model ISORROPIA-II. Modelled SO42-, NO3-, and NH3 values agree well with the measurements, while the modelled NH4+ values largely underestimate the measurements. Our observation and modelling results indicate that strong acids in aerosol are completely neutralised. Additional NH4+ exists in aerosol, probably a result of the presence of a substantial amount of oxalic and other diacids.

Physiological impacts and bioaccumulation of dietary Cu and Cd in a model teleost: The Amazonian tambaqui (Colossoma macropomum).

PubMed

Giacomin, Marina; Vilarinho, Gisele C; Castro, Katia F; Ferreira, Márcio; Duarte, Rafael M; Wood, Chris M; Val, Adalberto L

2018-06-01

Increasing anthropogenic activities in the Amazon have led to elevated metals in the aquatic environment. Since fish are the main source of animal protein for the Amazonian population, understanding metal bioaccumulation patterns and physiological impacts is of critical importance. Juvenile tambaqui, a local model species, were exposed to chronic dietary Cu (essential, 500 μg Cu/g food) and Cd (non-essential, 500 μg Cd/g food). Fish were sampled at 10-14, 18-20 and 33-36 days of exposure and the following parameters were analyzed: growth, voluntary food consumption, conversion efficiency, tissue-specific metal bioaccumulation, ammonia and urea-N excretion, O 2 consumption, P crit , hypoxia tolerance, nitrogen quotient, major blood plasma ions and metabolites, gill and gut enzyme activities, and in vitro gut fluid transport. The results indicate no ionoregulatory impacts of either of the metal-contaminated diets at gill, gut, or plasma levels, and no differences in plasma cortisol or lactate. The Cd diet appeared to have suppressed feeding, though overall tank growth was not affected. Bioaccumulation of both metals was observed. Distinct tissue-specific and time-specific patterns were seen. Metal burdens in the edible white muscle remained low. Overall, physiological impacts of the Cu diet were minimal. However dietary Cd increased hypoxia tolerance, as evidenced by decreased P crit , increased time to loss of equilibrium, a lack of plasma glucose elevation, decreased plasma ethanol, and decreased NQ during hypoxia. Blood O 2 transport characteristics (P 50 , Bohr coefficient, hemoglobin, hematocrit) were unaffected, suggesting that tissue level changes in metabolism accounted for the greater hypoxia tolerance in tambaqui fed with a Cd-contaminated diet. Copyright © 2018 Elsevier B.V. All rights reserved.

Evaluation of the Determination of Free Urea in Water-Soluble Liquid Fertilizers Containing Urea and Ureaforms by Urease and HPLC Methods.

PubMed

Hojjatie, Michael M; Abrams, Dean

2015-01-01

Currently there are three AOAC Official Methods for the determination of urea in fertilizers. AOAC Official Method 959.03, Urea in Fertilizers, Urease Method, First Action 1959, Final Action 1960, is based on the use of fresh commercial 1% urease solution, or preparation of such solution from urease powder in water, or from jack bean meal in water. AOAC Official Method 983.01, Urea and Methyleneureas (Water-Soluble) in Fertilizers, First Action 1983, Final Action 1984, is based on LC with a refractive index detector using water as the mobile phase and a C18 column. AOAC Official Method 2003.14, Determination of Urea in Water- Soluble Urea-Formaldehyde Fertilizer Products and in Aqueous Urea Solutions, First Action 2003, Final Action 2008, is based on LC with a UV detector using acetonitrile-water (85+15, v/v) mobile phase and a propylamine column. The urea method, AOAC Official Method 959.03, is very much dependent on the nature of the urease enzyme. The method was developed in 1960 and used for simple urea fertilizer solutions. With the advent of complex fertilizer compositions, especially with the class of liquid triazone fertilizers and water-soluble urea forms, the analyses of free urea in these fertilizers by the urease method is often inaccurate and inconsistent. AOAC Official Method 983.01 is not always reliable due to the interference of some of the components of these fertilizers, and due to the fact that the use of water as the mobile phase does not always separate the free urea from other components. AOAC Official Method 2003.14 was subjected to ring test studies that showed it could be used for the determination of "free urea" in these classes of fertilizers with good accuracy and precision.

CsNIP2;1 is a Plasma Membrane Transporter from Cucumis sativus that Facilitates Urea Uptake When Expressed in Saccharomyces cerevisiae and Arabidopsis thaliana.

PubMed

Zhang, Lu; Yan, Jiapei; Vatamaniuk, Olena K; Du, Xiangge

2016-03-01

Urea is an important source of nitrogen (N) for the growth and development of plants. It occurs naturally in soils, is the major N source in agricultural fertilizers and is an important N metabolite in plants. Therefore, the identification and characterization of urea transporters in higher plants is important for the fundamental understanding of urea-based N nutrition in plants and for designing novel strategies for improving the N-use efficiency of urea based-fertilizers. Progress in this area, however, is hampered due to scarce knowledge of plant urea transporters. From what is known, urea uptake from the soil into plant roots is mediated by two types of transporters: the major intrinsic proteins (MIPs) and the DUR3 orthologs, mediating low- and high-affinity urea transport, respectively. Here we characterized a MIP family member from Cucumis sativus, CsNIP2;1, with regard to its contribution to urea transport. We show that CsNIP2;1 is a plasma membrane transporter that mediates pH-dependent urea uptake when expressed in yeast. We also found that ectopic expression of CsNIP2;1 improves growth of wild-type Arabidopsis thaliana and rescues growth and development of the atdur3-3 mutant on medium with urea as the sole N source. In addition, CsNIP2;1 is transcriptionally up-regulated by N deficiency, urea and NO3 (-). These data and results from the analyses of the pattern of CsNIP2;1 expression in A. thaliana and cucumber suggest that CsNIP2;1 might be involved in multiple steps of urea-based N nutrition, including urea uptake and internal transport during N remobilization throughout seed germination and N delivery to developing tissues. © Crown copyright 2016.

Role of protein kinase C-α in hypertonicity-stimulated urea permeability in mouse inner medullary collecting ducts

PubMed Central

Klein, Janet D.; Froehlich, Otto; Sands, Jeff M.

2013-01-01

The kidney's ability to concentrate urine is vitally important to our quality of life. In the hypertonic environment of the kidney, urea transporters must be regulated to optimize function. We previously showed that hypertonicity increases urea permeability and that the protein kinase C (PKC) blockers chelerythrine and rottlerin decreased hypertonicity-stimulated urea permeability in rat inner medullary collecting ducts (IMCDs). Because PKCα knockout (PKCα−/−) mice have a urine-concentrating defect, we tested the effect of hypertonicity on urea permeability in isolated perfused mouse IMCDs. Increasing the osmolality of perfusate and bath from 290 to 690 mosmol/kgH2O did not change urea permeability in PKCα−/− mice but significantly increased urea permeability in wild-type mice. To determine whether the response to protein kinase A was also missing in IMCDs of PKCα−/− mice, tubules were treated with vasopressin and subsequently with the PKC stimulator phorbol dibutyrate (PDBu). Vasopressin stimulated urea permeability in PKCα−/− mice. Like vasopressin, forskolin stimulated urea permeability in PKCα−/− mice. We previously showed that, in rats, vasopressin and PDBu have additive stimulatory effects on urea permeability. In contrast, in PKCα−/− mice, PDBu did not further increase vasopressin-stimulated urea permeability. Western blot analysis showed that expression of the UT-A1 urea transporter in IMCDs was increased in response to vasopressin in wild-type mice as well as PKCα−/− mice. Hypertonicity increased UT-A1 phosphorylation in wild-type mice but not in PKCα−/− mice. We conclude that PKCα mediates hypertonicity-stimulated urea transport but is not necessary for vasopressin stimulation of urea permeability in mouse IMCDs. PMID:23097465

21 CFR 862.1770 - Urea nitrogen test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Urea nitrogen test system. 862.1770 Section 862....1770 Urea nitrogen test system. (a) Identification. A urea nitrogen test system is a device intended to measure urea nitrogen (an end-product of nitrogen metabolism) in whole blood, serum, plasma, and urine...

21 CFR 862.1770 - Urea nitrogen test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Urea nitrogen test system. 862.1770 Section 862....1770 Urea nitrogen test system. (a) Identification. A urea nitrogen test system is a device intended to measure urea nitrogen (an end-product of nitrogen metabolism) in whole blood, serum, plasma, and urine...

21 CFR 862.1770 - Urea nitrogen test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Urea nitrogen test system. 862.1770 Section 862....1770 Urea nitrogen test system. (a) Identification. A urea nitrogen test system is a device intended to measure urea nitrogen (an end-product of nitrogen metabolism) in whole blood, serum, plasma, and urine...

21 CFR 862.1770 - Urea nitrogen test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Urea nitrogen test system. 862.1770 Section 862....1770 Urea nitrogen test system. (a) Identification. A urea nitrogen test system is a device intended to measure urea nitrogen (an end-product of nitrogen metabolism) in whole blood, serum, plasma, and urine...

Phenol-Urea-Formaldehyde (PUF) co-condensed wood adhesives

Treesearch

Bunichiro Tomita; Chung-Yun Hse

1998-01-01

The reaction of urea with methylolphenol under acidic conditions was investigated. The alternating copolymer of urea and phenol could be synthesized by the reaction of urea and 2,4,6-trimethylolphenol. The reactions of urea with polymethylolphenol mixtures also were investigated by changing the reaction conditions, such as the molar ratio and acidity. The co-...

21 CFR 862.1770 - Urea nitrogen test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Urea nitrogen test system. 862.1770 Section 862....1770 Urea nitrogen test system. (a) Identification. A urea nitrogen test system is a device intended to measure urea nitrogen (an end-product of nitrogen metabolism) in whole blood, serum, plasma, and urine...