Increased Plasma Urea Concentrations Research Articles

Dapagliflozin Stimulates Renal Ammonia Excretion in Rats

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are drugs that induce glycosuria and are used to treat type 2 diabetes mellitus, moreover it has also been used in other conditions such as heart failure and atherosclerosis. However, little is known about the effects of these drugs on renal function. Considering that the maintenance of acid-base balance is closely related to renal physiology, in this study we evaluated the influence of chronic use of dapagliflozin on global renal function and urinary excretion of ammonia and titratable acids. Objective: To evaluate global renal function and urinary acid excretion (ammonia and titratable acid) in male Wistar rats chronically treated with dapagliflozin. Methods: 3-month-old male Wistar rats were randomized to control (C) and dapagliflozin (D) groups. Animals in group D received dapagliflozin (3 mg/kg, gavage) for 4 weeks. All animals were given food and water ad libitum throughout the experimental protocol. At 4 months of age, animals were placed in metabolic cages for 24-hour urine collection followed by blood sampling. Plasma concentrations of creatinine, sodium, potassium, urea, pH, pCO2, and bicarbonate were evaluated. The following were also evaluated: body weight, water intake, urine flow, and excretion of ammonia, titratable acids, glucose, and protein. Protocol approved by CEUA-UNIFESP number: 5985180423. Values expressed as mean ± standard error; number of animals per group: 6. Results: No significant changes were observed in blood gas parameters: pH (C: 7.33±0.043; D: 7.36±0.027), pCO2 (C: 53.30±2.40; D: 52.67±3.63 mmHg) and HCO3− (C: 27.07±1.31; D: 29.75±1.72 mEq/L) and no significant changes in plasma creatinine concentration (C: 0.41±0.04; D: 0.40±0.04mg/dl), Na+ (C: 144±0.47; D: 137±2.04 mmol/l) and K+ (C: 4.30±0.21; D: 4.16±0.20 mmol/l). We observed a significant increase in urine flow (C: 0.027±0.006; D: 0.068±0.005 mL/min/kg), possibly associated with intense glycosuria (C: 0.017±0.005; D: 8.97±0.51 g/24h). The significant increase in plasma urea concentration (C: 39.17±2.57; D: 48.83±1.27 mg/dL) and proteinuria (C: 11.04±0.30; D: 15.79±0.56 mg/24h) may indicate some renal impairment. Considering the marked increase in urinary excretion of ammonia (C: 0.65±0.05; D: 3.49±2.31 mEq/24h) and titratable acids (C: 0.180±0.036; D: 0.628±0.078 mEq/24h), we can conclude that the drug-induced glycosuria may lead to biochemical adaptations to maintain blood glucose levels within the normal range, at the expense of increased metabolic acid production. However, further experiments are needed to confirm this hypothesis. CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Combined Intake of Fish Oil and D-Fagomine Prevents High-Fat High-Sucrose Diet-Induced Prediabetes by Modulating Lipotoxicity and Protein Carbonylation in the Kidney.

Obesity has been recognized as a major risk factor for chronic kidney disease, insulin resistance being an early common metabolic feature in patients suffering from this syndrome. This study aims to investigate the mechanism underlying the induction of kidney dysfunction and the concomitant onset of insulin resistance by long-term high-fat and sucrose diet feeding in Sprague Dawley rats. To achieve this goal, our study analyzed renal carbonylated protein patterns, ectopic lipid accumulation and fatty acid profiles and correlated them with biometrical and biochemical measurements and other body redox status parameters. Rats fed the obesogenic diet developed a prediabetic state and incipient kidney dysfunction manifested in increased plasma urea concentration and superior levels of renal fat deposition and protein carbonylation. An obesogenic diet increased renal fat by preferentially promoting the accumulation of saturated fat, arachidonic, and docosahexaenoic fatty acids while decreasing oleic acid. Renal lipotoxicity was accompanied by selectively higher carbonylation of proteins involved in the blood pH regulation, i.e., bicarbonate reclamation and synthesis, amino acid, and glucose metabolisms, directly related to the onset of insulin resistance. This study also tested the combination of antioxidant properties of fish oil with the anti-diabetic properties of buckwheat D-Fagomine to counteract diet-induced renal alterations. Results demonstrated that bioactive compounds combined attenuated lipotoxicity, induced more favorable lipid profiles and counteracted the excessive carbonylation of proteins associated with pH regulation in the kidneys, resulting in an inhibition of the progression of the prediabetes state and kidney disease.

Divergent regulation of lncRNA expression by ischemia in adult and aging mice

Elderly patients have increased susceptibility to acute kidney injury (AKI). Long noncoding RNAs (lncRNA) are key regulators of cellular processes, and have been implicated in both aging and AKI. Our aim was to study the effects of aging and ischemia–reperfusion injury (IRI) on the renal expression of lncRNAs. Adult and old (10- and 26–30-month-old) C57BL/6 N mice were subjected to unilateral IRI followed by 7 days of reperfusion. Renal expression of 90 lncRNAs and mRNA expression of injury, regeneration, and fibrosis markers was measured by qPCR in the injured and contralateral control kidneys. Tubular injury, regeneration, and fibrosis were assessed by histology. Urinary lipocalin-2 excretion was increased in old mice prior to IRI, but plasma urea was similar. In the control kidneys of old mice tubular cell necrosis and apoptosis, mRNA expression of kidney injury molecule-1, fibronectin-1, p16, and p21 was elevated. IRI increased plasma urea concentration only in old mice, but injury, regeneration, and fibrosis scores and their mRNA markers were similar in both age groups. AK082072 and Y lncRNAs were upregulated, while H19 and RepA transcript were downregulated in the control kidneys of old mice. IRI upregulated Miat, Igf2as, SNHG5, SNHG6, RNCR3, Malat1, Air, Linc1633, and Neat1 v1, while downregulated Linc1242. LncRNAs H19, AK082072, RepA transcript, and Six3os were influenced by both aging and IRI. Our results indicate that both aging and IRI alter renal lncRNA expression suggesting that lncRNAs have a versatile and complex role in aging and kidney injury. An Ingenuity Pathway Analysis highlighted that the most downregulated H19 may be linked to aging/senescence through p53.

Zinc-methionine supplementation prevents the live weight loss in the early lactation of Ongole-Crossbred cows in the reproduction cycle

This research aimed to investigate the reproductive performance of Ongole crossbred (PO) cows offered zinc methionine (ZincMeth) during the late gestation and early lactation. Thirty-two PO pregnant cows, 400 kg live weight (LW) were weighed and measured body condition score (BCS) before the experiment. The experimental design was a 2 x 2 factorial with two nutritional and two ZincMeth treatments, with eight cows in each nutrition x ZincMeth group. All cows were offered elephant grass (EG), 16 cows offered a concentrate diet (CONS) containing 15% crude protein (CP) and 16 cows offered a CONS containing 11% CP at 3% LW on a DM basis, the ratio of EG: CONS was 40:60. Five grams of ZincMeth was added to the CONS prepared for individual cows. The parameters observed were LW gain, BCS, post-partum anestrus period, luteinizing hormone, volatile fatty acid, and blood metabolite concentrations. The results showed that the BCS change was greater in cows fed a high CP diet, they also had high plasma glucose, urea, and total protein concentrations. ZincMeth prevented LW loss in the early lactation and increased plasma urea concentration. Thus, the ZincMeth maintained the LWG during the critical period but did not affect any reproductive parameters.

220-LB: Glucagon Promotes Hepatic Autophagy by AMPK-Mediated mTORC1 Inhibition

Glucagon plays an important role in hepatic glucose metabolism as well as protein/amino acid metabolism but detailed knowledge about glucagon’s role in hepatic autophagy is limited. We hypothesized that glucagon regulate hepatic protein metabolism partly through activation of AMP-kinase (AMPK) that in turn lead to inhibition of mammalian target of rapamycin complex1 (mTORC1) and activation of Uncoordinated-51 like autophagy activating kinase-1 (ULK1) resulting in increased autophagy. In order to test this hypothesis, we infused chronically catheterized awake mice with [13C5]-glutamine [0.225 mg/(kg-min)] for 120 min after which a second line was connected infusing somatostatin [4 µg/(kg-min)] and insulin [0.1 mU/(kg-min)], with (n=7) or without glucagon [10 ng/(kg-min)] (n=6) for 90 min. This raised plasma glucagon concentration ~18-fold compared to control. Glucagon infusion increased phosphorylation of hepatic: AMPKThr172, RaptorSer792, ULK1Ser555 (P=0.03, P=0.03, and P=0.06, respectively, compared to control), and resulted in hepatic Microtubule-associated protein 1A/1B-light chain 3 (LC3)-II accumulation (P=0.02), a marker of autophagy, assessed by immunoblotting. Glucagon treatment also increased the 13C enrichment (m+3) in liver glucose (P<0.0001), indicating increased conversion of [13C5]-glutamine to glucose as well as increased plasma urea concentrations (P=0.04). Consistent with these in vivo results, parallel studies performed in liver slices obtained from overnight fasted male rats (n=6) incubated in Krebs-Henseleit bicarbonate buffer supplemented with [3-13C]-alanine (1 mM), glucagon (250 µM) treatment increased: glucose production (P=0.01), urea production (P=0.0005), and intracellular levels of leucine (P=0.045). In conclusion, our data suggest that glucagon promotes hepatic proteolysis and ureagenesis by AMPK-mediated suppression of mTOC1 activity, leading to increased hepatic autophagy. Disclosure K.D. Galsgaard: None. N.J. Wewer Albrechtsen: Research Support; Self; Mercodia, Novo Nordisk A/S, Novo Nordisk Foundation. Speaker’s Bureau; Self; Merck Sharp & Dohme Corp. J.J. Holst: Advisory Panel; Self; AstraZeneca, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Zealand Pharma A/S. Other Relationship; Spouse/Partner; Antag Therapeutics. G.I. Shulman: Advisory Panel; Self; AstraZeneca, Janssen Research & Development, LLC, Merck & Co., Inc. Advisory Panel; Spouse/Partner; Merck & Co., Inc. Consultant; Self; Novo Nordisk A/S. Consultant; Spouse/Partner; Novo Nordisk A/S. Other Relationship; Self; Gilead Sciences, Inc., iMetabolic Biopharma Corporation. Other Relationship; Spouse/Partner; iMetabolic Biopharma Corporation. Other Relationship; Self; Maze Therapeutics. K. Petersen: Advisory Panel; Spouse/Partner; Merck Sharp & Dohme Corp. Research Support; Self; Merck Sharp & Dohme Corp., National Institute of Diabetes and Digestive and Kidney Diseases. Research Support; Spouse/Partner; National Institute of Diabetes and Digestive and Kidney Diseases. A. Nasiri: Employee; Spouse/Partner; Medtronic. G. Cline: None. X. Zhang: None. J. Lee: None. B.T. Hubbard: None.

Effect of SOYXYL as a Dietary Protected Protein Supplement on the Reproductive Performance of Simmental Bulls

The study aimed to evaluate the effect of SOYXYL as one of the dietary protected protein supplement product in the rations on the reproduction performance of Simmental bulls. Twelve 5 years-old Simmental bulls were allotted to 4 treatment groups with 3 replications in each, i.e.: T0= control ration (elephant grass + 5 kg/head/day commercial concentrate), T1= control ration + 150 g protected protein supplement SOYXYL (3% of concentrate), T2 = control ration + 300 g SOYXYL (6% of concentrate) and T3= control ration + 450 g SOYXYL (9% of concentrate). The experiment lasted for 90 days. At the end of the experiment, semen and blood were collected and body weight gain was measured. The variables measured included sperm motility, sperm concentration, blood protein, blood urea and the concentration of testosterone. Results showed that SOYXYL supplementation, particularly at the levels of 3 and 6%, increased the total plasma protein of bulls. SOYXYL supplementation at 3% from concentrate resulted in increased plasma urea concentration. Feeding SOYXYL, particularly at the levels of 6 and 9%, increased the average daily gain of bulls as compared to control. Feeding 3% SOYXYL increased, but at the levels of 6 and 9% decreased the concentration of sperm of bulls. The concentration of testosterone was higher in the bulls received 3 and 6% SOYXYL in the rations. Dietary supplementation of SOYXYL increased the sperm motility of Simmental bulls. In conclusion, dietary supplementation of SOYXYL at the level of 3% increased plasma protein, testosterone, and sperm concentrations as well as sperm motility. However, supplementation of SOYXYL at 6 and 9% from rations decreased the concentrations of sperm and testosterone.

Dipeptiven® improves kidney pathology in a rat model of chronic kidney disease

Summary Background & aims Administration of glutamine in patients with renal dysfunction is considered to be potentially adverse. In a rat model of moderate kidney dysfunction dose-dependent effects of intravenous alanyl-glutamine infusion on possible biochemical and histological signs of toxicity were investigated. Methods Rats with renal dysfunction resulting from 5/6 nephrectomy received a 9 days continuous intravenous infusion of either saline or 0.5 g/kg/day or 3.0 g/kg/day alanyl-glutamine (Dipeptiven®) or 3.0 g/kg/day alanine. Dose-dependent effects on kidney and other organs were assessed by analyzing blood levels of creatinine, ammonia, urea, ALT, AST, ALP, pH, pO2, pCO2, glutamine, and histopathology. Results Continuous intravenous infusion of 3.0 g/kg/day alanyl-glutamine increased plasma glutamine concentrations up to 60% without aggravating the underlying kidney injury. In contrast, the morphology of the kidneys was improved due to reduced glomerulosclerosis and tubular proteinaceous casts. An increase in plasma urea concentrations observed in the 3.0 g/kg/day alanyl-glutamine group only was not associated with worsening of the phenotype. Conclusions Continuous intravenous infusion of alanyl-glutamine at 0.5 and 3.0 g/kg/day up to 9 consecutive days is safe in a rat model of chronic moderate kidney dysfunction and improved the renal morphology by reducing glomerulosclerosis and tubular proteinaceous casts. In these animals a decreased incidence and severity of chronic progressive nephropathy was observed compared to the saline and alanine treated animals.

The para isomer of dinitrobenzene disrupts redox homeostasis in liver and kidney of male wistar rats

BackgroundPara-Dinitrobenzene (p-DNB) is one of the isomers of dinitrobenzene which have been detected as environmental toxicants. Skin irritation and organ toxicities are likely for industrial workers exposed to p-DNB. This study evaluated the effect of sub-chronic exposure of rats to p-DNB on cellular redox balance, hepatic and renal integrity. MethodsForty eight male Wistar rats weighing 160–180g were administered 50, 75, 1000 and 2000mg/kg b.wt (body weight) of p-DNB or an equivalent volume of vehicle (control) orally and topically for 14 days. After the period of treatment, the activities of kidney and liver catalase (CAT), alkaline phosphatase (ALP) and superoxide dismutase (SOD) as well as extent of renal and hepatic lipid peroxidation (LPO) were determined. Serum ALP activity and plasma urea concentration were also evaluated. ResultsCompared with control animals, p-DNB -administered rats showed decrease in the body and relative kidney and liver weights as well as increased renal and hepatic hydrogen peroxide and lipid peroxidation levels accompanied by decreased superoxide dismutase and catalase activities. However, p-DNB caused a significant increase in plasma urea concentration and serum, liver and kidney ALP activities relative to control. In addition, p-DNB caused periportal infiltration, severe macro vesicular steatosis and hepatic necrosis in the liver. ConclusionsOur findings show that sub-chronic oral and sub-dermal administration of p-DNB may produce hepato-nephrotoxicity through oxidative stress.

Acute and subchronic toxicity studies of the new quinolone antibacterial agent irloxacin in rodents.

Irloxacin (6-fluorine-7-(pyrrol-1-yl)-1-ethyl-1, 4-dihydro-4-oxo-quinolone-3-carboxylic acid, CAS 91524-15-1), a new quinolone antibacterial agent, was administered as a single dose to rats and mice both by oral and intraperitoneal route in oder to study its acute toxicity. Its oral subchronic toxicity was also assessed by treating rats for 4 and 13 weeks. The results obtained showed that irloxacin was well tolerated after single administration in mice and rats, with LD50 values above 2000 and 5000 mg/kg for intraperitoneal and oral administration, respectively. In the oral subchronic toxicity studies, the histopathological examination performed after the 13-week treatment period confirmed the kidney as the target organ for toxicity. Increased presence of lipofuscin in the kidneys was observed in animals receiving 2000 or 450 mg/kg/d, and degeneration and/or dilatation of proximal renal tubules and chronic interstitial nephritis in males receiving these dosages. No histopathological findings were observed in the kidneys of animals receiving 100 mg/kg/d for 13 weeks. Other relevant findings were, presence of dark or cloudy urine with slightly lower pH in animals receiving dosages of 450 mg/kg/d and above, increased urinary protein concentration in animals receiving 2000 or 450 mg/kg/d, and increased plasma urea concentration in those receiving 2000 mg/kg/d. Moreover, increased plasma phospholipids and total cholesterol concentration, and increased liver and kidney weights were observed among treated animals. As a summary, the results have shown that irloxacin has a low acute toxicity in both mice and rats. For repeat oral administration in rats, 100 mg/kg can be considered as the non-toxic effect level after a treatment period of 13 weeks.

An Investigation into the Effects of Aminoguanidine Treatment on the Plasma and Blood of Free-fed and Dietary-restricted Rats

An investigation has been made into the effect of oral aminoguanidine (50-60 mg kg-1 day-1) on the blood biochemistry of male Wistar rats which either had free access to food or were dietary-restricted (50% of the food consumed by the free access group). In control rats (i.e. without aminoguanidine treatment) three weeks of food restriction caused significant increases in plasma sodium and albumin and the erythrocyte count, haematocrit and haemoglobin. There were reductions in plasma calcium, phosphate, alkaline phosphatase activity, urea, triglycerides, creatinine, glucose and the red cell volume. Similar effects of food restriction were observed in aminoguanidine-treated rats. Aminoguanidine ingestion in free-fed animals caused a reduction in plasma creatinine concentration. In dietary-restricted rats, aminoguanidine ingestion reduced plasma sodium and total plasma proteins (largely as a result of a decline in albumin), and increased plasma urea concentrations. Aminoguanidine was added to plasma of control rats in-vitro to determine whether it interfered with the assay of urea and creatinine. At concentrations of 0.1 to 10 mg mL-1, aminoguanidine had no effect on urea determinations. However, aminoguanidine significantly reduced the apparent concentration of plasma creatinine by between 7 to 81%. The changes in plasma analytes in aminoguanidine-treated rats may be indicative of minor hepatic perturbations or kidney function, but the data also imply that prior nutritional state is a determinant of aminoguanidine effects.

Effect of extruded fodder on biochemical and haematological parameters of Standardbred horses under training conditions

The aim of this study was to examine whether feeding of extruded fodder can improve the energy metabolism of horses under training conditions. The experiment was performed on 12 clinically healthy Standardbred horses (6 horses in the control group and 6 horses in the experimental group). The diet of the horses was based on oats, barley, meadow hay, and a supplement of vitamins and minerals. The diet of the experimental group (6 horses) was supplemented with 1.25 kg of extruded fodder that replaced the corresponding dose of grain. Feeding doses were related to the rate of sub-maximal workload. Selected biochemical parameters of energy and protein metabolism, electrolytes, and haematological parameters were monitored at rest and 5 min after exercise at the beginning and at the end of the 10-week experimental period. The 10 weeks of the training period resulted in a significant decrease in serum glucose concentration, serum total proteins, and plasma creatinine concentration, and a significant increase in plasma urea concentration and haemoglobin in both groups of horses at rest. Post-exercise a significant increase in blood urea levels and a decrease in total proteins in both groups demonstrated that the proteins became sources of energy. A significant increase in the haemoglobin level together with a significant decrease in the creatinine level in the horses of both groups at the end of the experiment indicated an increased aerobic metabolism. Nevertheless, extruded fodder in the horses' diet did not have the anticipated effect.

Subcellular distribution of urea transporter in the collecting tubule of shark kidney is dependent on environmental salinity

In the kidney of marine elasmobranchs, urea reabsorption from filtered urine is essential for maintaining high levels of urea in the body. In the kidney of the houndshark, Triakis scyllium, we previously found that a facilitative urea transporter (UT) is localized to a specific nephron segment, the collecting tubule, suggesting that the collecting tubule has an important role in the urea reabsorption process. To elucidate the roles of UT, we transferred T. scyllium to high (130%) and low (30%) salinity, and examined UT mRNA levels and UT distribution patterns in the kidney using real-time PCR and semi-quantitative fluorescence immunohistochemistry, respectively. Following transfer to low and high salinity, houndshark decreased and increased plasma urea concentrations, respectively, in order to control plasma osmolality. The abundance of UT mRNA did not differ among the experimental groups, whereas that of UT protein in the collecting tubule was significantly decreased in 30% seawater (SW). Furthermore, the subcellular UT distribution was dramatically changed. UT in the apical plasma membrane of collecting tubule almost disappeared in 30% SW, whereas it slightly increased in 130% SW compared with 100% SW. Conversely, reverse transfer of fish from 30 to100% SW restored UT in the apical membrane. These results indicate that the accumulation of UT to the apical plasma membrane of the collecting tubule of Triakis is an important factor for regulating urea reabsorption in the kidney.

Changes of activity and mRNA expression of urea cycle enzymes in the liver of developing Holstein calves1

Urea is an important reutilizable nitrogen source for the ruminant and is mainly synthesized through the urea cycle in the liver. The cycle is undertaken by 5 enzymes: carbamoyl phosphate synthetase (CPS), ornithine transcarbamoylase (OTC), arginino-succinate synthetase (AS), argininosuccinate lyase (AL), and arginase. The purpose of this study was to investigate changes in the activity of the enzymes and mRNA expression, given that previous observations have indicated an increase in plasma urea concentrations with age in Holstein calves. First, plasma concentrations of metabolites and hormones were determined in calves at 1, 3, 8, 13, and 19 wk of age (n = 4, weaned at 6 wk of age). The plasma concentration of urea drastically increased after weaning (P < 0.001). The plasma concentration of glucose was lowest at 8 wk. The plasma concentration of IGF-I gradually increased with age, although those of NEFA, glucagon, and cortisol decreased (P < 0.001). Concentrations of triglyceride, alpha-amino nitrogen, growth hormone, and insulin did not change significantly with age of the calf. Next, using the liver tissues taken from calves at 2, 13, and 19 wk of age (n = 4 to 6 at each time point, weaned at 6 wk of age), we measured the activity and mRNA expression of the enzymes by biochemical methods and quantitative reverse transcription-PCR, respectively. The activities of CPS (P < 0.001), OTC (P = 0.001), and AS (P = 0.015) increased with age, whereas AL (P = 0.003) decreased. Although mRNA expression was decreased with age for AL (P = 0.002) and arginase (P = 0.007), no significant change was observed for CPS, OTC, or AS mRNA expression. We conclude that the increased urea production in the liver may be explained not only by an increase in the activities of the urea cycle enzymes, but also by increased ammonia production by rumen fermentation and gluconeogenesis from amino acids around weaning time.

Idiopathic Immune‐Mediated Hemolytic Anemia: Treatment Outcome and Prognostic Factors in 149 Dogs

Canine idiopathic immune-mediated hemolytic anemia (IMHA) is associated with a high mortality, especially in the 1st 2 weeks after diagnosis despite treatment. To determine treatment outcome and identify prognostic variables in order to define areas of future research. One hundred forty-nine dogs with hematocrit <30% and either a positive Coombs' test or spherocytosis and with no evidence of disease that can trigger IMHA were included. Retrospective cohort study. All dogs were treated with prednisolone and azathioprine according to a standard protocol. Survival analysis was performed by the Kaplan-Meier method. Variables recorded at the time of diagnosis were tested as possible prognostic variables in a univariate and multivariate Cox proportional hazard model. The main predictors for mortality in dogs with idiopathic IMHA are the presence of increased plasma urea concentration, bands, thrombocytopenia, and petechiae at the time of diagnosis. The estimated Kaplan-Meier half-year survival was 72.6% (95% confidence interval [CI]: 64.9-81.3%). Mortality occurred mostly within the 1st 2 weeks. Cox proportional hazards analysis indicated that increased plasma urea concentration, icterus, and petechiae were the major independent predictors of mortality in the 1st 2 weeks. In most dogs that survived IMHA, a 3-month protocol of azathioprine with prednisolone maintained clinical remission. The estimated half-year survival for dogs that survived the 1st 2 weeks was 92.5% (95% CI: 86-99.3%). If the dogs survived IMHA, a 3-month protocol of prednisolone and azathioprine was effective with regard to survival and clinical outcome. Future research should be directed at identifying whether thrombotic tendency in dogs with IMHA is the main contributor to the development of increased plasma urea concentration, icterus, thrombocytopenia, and petechiae.

Effects of Dietary Protein and Starch on Intake, Milk Production, and Milk Fatty Acid Profiles of Dairy Cows Fed Corn Silage-Based Diets

Feed intake, milk production, and milk fatty acid profiles of dairy cows fed corn silage-based diets with different protein and starch concentrations were measured in a 3-period experiment in a changeover design using 12 Holstein cows. Each experimental period lasted for 3 wk. The diet fed as a total mixed ration consisted of 45% corn silage, 5% coarsely chopped wheat straw, and 50% concentrate, on a dry matter (DM) basis. The 4 treatments, formulated to be isoenergetic and to differ in concentrations of dietary crude protein (CP) and starch (DM basis), were as follows: low CP and low starch (LPLS; 14% CP and 15% starch), low CP and high starch (LPHS; 14% CP and 25% starch), high CP and low starch (HPLS; 16% CP and 15% starch), and high CP and high starch (HPHS; 16% CP and 25% starch). The LPLS treatment led to lower DM intake, milk yield, milk protein concentration, and milk lactose yield, probably due to a shortage of both rumen-degradable protein supply to rumen microbes and glucogenic nutrients to the animal. There were no differences between protein-rich diets and LPHS, suggesting that this diet satisfied the rumen-degradable protein requirements of rumen microbes and did not limit feed intake, and the increased supply of glucogenic nutrients spared AA so that the nutrient requirements of mid lactation dairy cows were met. Further increases in CP concentration increased plasma urea concentration and resulted in decreased efficiency of conversion of dietary N into milk N. Milk fatty acid profiles were affected by starch and protein supply, with starch having the largest effect. Additionally, increasing dietary starch concentration decreased the apparent transfer of dietary polyunsaturated fatty acids to milk, suggesting an increased channeling of fatty acids to adipose tissue. The results further suggest that C15:0 and C17:0 are synthesized de novo in animal tissues.

Screening for increased plasma urea levels in a large-scale ENU mouse mutagenesis project reveals kidney disease models

Kidney diseases lead to the failure of urinary excretion of metabolism products. In the Munich ethylnitrosourea (ENU) mouse mutagenesis project, which is done on a C3H inbred genetic background, blood samples of more than 15,000 G1 offspring and 500 G3 pedigrees were screened for alterations in clinical-chemical parameters. We identified 44 animals consistently exhibiting increased plasma urea concentrations. Transmission analysis of the altered phenotype of 23 mice to subsequent generations led to the establishment of five mutant lines. Both sexes were affected in these lines. Urinary urea levels were decreased in the mutants. In addition, most mutants showed increased plasma and decreased urinary creatinine levels. Pathological investigation of kidneys from the five mutant lines revealed a broad spectrum of alterations, ranging from no macroscopic and light microscopic kidney alterations to decreased kidney weight-to-body weight ratio, dilation of the renal pelvis, and severe glomerular lesions. Thus screening for elevated plasma urea levels in a large-scale ENU mouse mutagenesis project resulted in the successful establishment of mouse strains which are valuable tools for molecular studies of mechanisms involved in urea excretion or which represent interesting models for kidney diseases.

Impact des nitrates inorganiques sur l’aspect morphofonctionnel du rein chez le rat

AimThe aim of our experimental study was to determine the effect of exogenic nitrates on certain biological parameters in relation to renal insufficiency. ResultsChronic treatment of rats for 5 months with varying nitrate concentrations (50, 100, 150 and 500 mg/L) induced a dose-dependent reduction in plasma concentrations of total proteins and a dose-dependent increase in plasma urea concentrations and creatinine. DiscussionThis histological study of the kidney shows that nitrates at doses of 150 and 500 mg/L cause a deterioration in the epithelia of the renal tubules. ConclusionIn conclusion, a high nitrate intake induces morphofunctional disturbances of the kidney and could thus be regarded as a causative factor in renal insufficiency.

Glucocorticoid receptors are involved in the regulation of pulsatile urea excretion in toadfish

The objectives of this study were to characterize the pattern of pulsatile urea excretion in the gulf toadfish in the wake of exogenous cortisol loading and to determine the receptors involved in the regulation of this mechanism. Toadfish were fitted with indwelling arterial catheters and were infused with isosmotic NaCl for 48 h after which fish were treated with cortisol alone, cortisol + peanut oil, cortisol + RU486 (a glucocorticoid receptor antagonist) or cortisol + spironolactone (a mineralocorticoid receptor antagonist). Upon cortisol loading, fish treated with cortisol alone, cortisol + oil or cortisol + spironolactone experienced a two- to threefold reduction in pulsatile urea excretion. This reduction was due to a decrease in urea pulse size with no effect on pulse frequency compared to values measured during the control NaCl infusion period. In addition, these fish showed an increase in plasma urea concentrations upon treatment. These apparent effects of cortisol treatment were abolished in fish treated with cortisol + RU486. In contrast, these fish showed an increase in pulsatile urea excretion mediated by a twofold increase in pulse size with no change in frequency. Likewise, fish treated with cortisol + RU486 showed a significant decrease in plasma urea concentrations over the course of the experiment. The findings of this study indicate that high levels of cortisol reduce pulsatile urea excretion by decreasing pulse size. In addition, it appears that glucocorticoid receptors and not mineralocorticoid receptors are involved in the regulation of the toadfish pulsatile urea excretion mechanism.

Nitrogen utilisation by dairy cows fed diets differing in crude protein level with a deficit in ruminal fermentable nitrogen

We studied the efficiency of nitrogen utilisation by dairy cows, using three diets differing in the crude protein (CP) level but with similar deficits (10 g x kg(-1) dry matter, DM) in ruminal fermentable nitrogen. There was no difference in milk yield from the cows offered the three diets (130, 145 and 160 g CP x kg(-1) DM). The milk protein content differed between the two most extreme diets (28.9 vs. 29.9 g x kg(-1), P < 0.05), resulting in higher protein yields for the highest CP treatment (P < 0.01). The efficiency of nitrogen utilisation, calculated as the proportion of ingested nitrogen recovered in the milk, was significantly higher for the 130 g CP x kg(-1) DM diet than for the other two diets (0.37 vs. 0.33 and 0.32 respectively. P < 0.01). The different diets also resulted in different levels of nitrogen excretion into the environment (237, 270 and 330 g N x d(-1), P < 0.01). Hepatic deamination of the amino acids may have generated additional energy to enable the animal to make use of the additional nitrogen in the diet, resulting in an increase in plasma urea concentration.

Effect of dietary energy and protein on bovine follicular dynamics and embryo production in vitro: associations with the ovarian insulin-like growth factor system.

Heifers were assigned either low or high (HE) levels of energy intake and low or high concentrations of dietary crude protein. The effect of these diets on the plasma concentrations of insulin, insulin-like growth factor (IGF)-I, and urea on follicular growth and early embryo development is described. We propose that the observed dietary-induced changes in the ovarian IGF system increase bioavailability of intrafollicular IGF, thus increasing the sensitivity of follicles to FSH. These changes, in combination with increased peripheral concentrations of insulin and IGF-I in heifers offered the HE diet, contribute to the observed increase in growth rate of the dominant follicle. In contrast to follicular growth, increased nutrient supply decreased oocyte quality, due in part to increased plasma urea concentrations. Clearly a number of mechanisms are involved in mediating the effects of dietary energy and protein on ovarian function, and the formulation of diets designed to optimize cattle fertility must consider the divergent effects of nutrient supply on follicular growth and oocyte quality.