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PubMed2001

[Rapid urease test].

The rapid urease test is a simple, sensitive, and highly specific test that enables the endoscopist to diagnose Helicobacter pylori infection in the endoscopy room. Determination of the infection status of Helicobacter pylori by biopsies from the gastric body had a significantly higher sensitivity than antral biopsies. A false-negative reaction by rapid urease test occurred the use of antibiotics (correlates with clearance of the bacteria) and the use of proton pump inhibitor or a part of mucosal protective agents(correlates urease inhibitory effect) and in the case of non-urease producing Helicobacter pylori. The rapid urease test satisfactory overall sensitivity before eradication treatment. However, the sensitivity of these rapid urease tests was lower after eradication than before eradication.

Clinical Enzyme Tests↗
PubMedDate not supplied

Rapid urease test utility for Helicobacter pylori infection diagnosis in gastric ulcer disease.

BACKGROUND/AIMS: To establish rapid urease test utility for initial diagnosis of Helicobacter pylori infection in gastric ulcer patients and to determine the best site for sampling for gastric biopsies. METHODOLOGY: Seventy consecutive gastric ulcer patients were prospectively studied. All these patients underwent three biopsies from both antrum and body (two for hematoxylin-eosin staining and one for rapid urease test -Jatrox H. p. Test-). Likewise, IgG ELISA serology and 13C-urea breath test were carried out. Gold standard for H. pylori infection was defined as two or more tests (i.e., histology, serology, breath test) with positive results. RESULTS: Rapid urease test yielded 96.8% sensitivity (95% CI = 89-99%) and 100% (66-100%) specificity when using biopsy specimens from the body, with identical results when biopsy specimens from both antrum and body were considered together. However, when only biopsy specimens from the antrum were used, sensitivity dropped to 72.6% (60-82%) and specificity was 100% (66-100%). As far as concordance between rapid urease test and histology is concerned, we found a "proportion of positive agreement" of 0.78 for the antrum, with 0.46 kappa statistic (P < 0.0001) and 15 McNemar statistic (P < 0.0001). For the gastric body, "proportion of positive agreement" was 0.98, with 0.94 kappa statistic (P < 0.0001) and 1 McNemar statistic (P = 0.3). Larger (P < 0.01) prevalence of both glandular atrophy (17.8%, 11-28%) and intestinal metaplasia (68.5%, 57-78%) was observed in the antrum in comparison with that in the body (4.1%, 1-11%; and 16.4%, 10-26%, respectively). CONCLUSIONS: Biopsy specimens from the body should always be obtained when the rapid urease test is performed to diagnose H. pylori infection in gastric ulcer, since this procedure is less accurate when biopsy specimens from the antrum are used, probably due to larger prevalence of both glandular atrophy and intestinal metaplasia in the latter site. Likewise, it seems that rapid urease test from body biopsies is sufficient to reach a reliable infection diagnosis in gastric ulcer patients as this procedure performed with antrum biopsies fails to improve its overall results.

Aged↗
PubMed2003

Role of ELISA in H. pylori detection and its correlation with urease test.

Helicobacter pylori is one of the most common chronic bacterial infection in humans linked to acid peptic diseases, gastric carcinomas and lymphomas. The bacilli produces large amounts of urease and this property has formed the basis of detection of H. pylori by the Christensen's urease test. Where endoscopy is not clinically indicated, serology may be used to establish the diagnosis. This study was undertaken to diagnose H. pylori with the help of Christensen's urease test on endoscopic biopsy specimens & correlated with the detection in Sera, of IgG antibodies against H. pylori, by ELISA technique. The study was conducted on 100 patients suffering from acid peptic disorders out of which 40 (40%) tested positive for H. pylori both by urease and serology. Christensen's urease and ELISA were found to have sensitivities of 85.7% & 90.9% and specificities of 96% and 87.5% respectively. Christensen's urease was taken as a standard method of diagnosis and its correlation with ELISA worked out to (+1) which meant there was a strong positive association between both the tests. Hence either test could be used for primary diagnosis of H. pylori instead of histopathological study and/or culture of H. pylori.

Antibodies, Bacterial↗
PubMedDate not supplied

[Inhibition of urease by cyclic beta-triketones and fluoride ions].

Competitive inhibition of soybean urease by 11 cyclic beta-triketones was studied in aqueous solutions at pH 7.4 and 36 degrees C. This process was characterized quantitatively by the inhibition constant (Ki), which showed a strong dependence on the structure of organic chelating agents (nickel atoms in urease) and varied from 58.4 to 847 microM. Under similar conditions, the substrate analogue (hydroxyurea) acted as a weak urease inhibitor (Ki = 6.47 mM). At 20 degrees C, competitive inhibition of urease with the ligand of nickel atoms (fluoride anion) was pH-dependent. At pH 3.85-6.45, the value of Ki for the process ranged from 36.5 to 4060 microM. Three nontoxic cyclic beta-triketones with Ki values of 58.4, 71.4, and 88.0 microM (36 degrees C) were the most potent inhibitors of urease. Their efficacy was determined by the presence of three >C=O- groups in the molecule and minimum steric hindrances to binding with metal sites in soybean urease.

Fluorides↗
PubMedDate not supplied

Rapid urease test from non-ulcer part of stomach is superior to histology from ulcer in detection of Helicobacter pylori infection in patients with gastric ulcer.

BACKGROUND/AIMS: Helicobacter pylori is the major pathogenesis of peptic ulcer disease. It is important for the endoscopists to detect H. pylori infection during endoscopy. Only one endoscopic diagnostic method can be used due to the limitation of health insurance payments in Taiwan. Most endoscopists use the tissue obtained from the ulcer margins for histopathological examination and detection of H. pylori infection in patients with gastric ulcer. Whether this is suitable deserves study. METHODOLOGY: A total of 103 consecutive subjects with gastric ulcer were recruited. Biopsy specimens from the margins of gastric ulcer were sent for histological examination with modified Giemsa stain. Two biopsy specimens from the antrum and greater curvature site of mid body were embedded in rapid urease test (CLOtest). A patient was classified as H. pylori positive if either CLOtest or histology were positive. RESULTS: 57 patients had H. pylori infection. The detection rate of rapid urease test and histological examination was 96.5% (55/57) and 59.6% (35/57), respectively. Of the 3 patients who had positive histological examinations and negative urease test, only one was confirmed again to have H. pylori infection. The detection rates of rapid urease test and histological examination in different locations of ulcer (antrum/angularis/proximal stomach) were 92.6%/100%/100% and 81.5%/42.1%/36.4%, respectively. CONCLUSIONS: Our study shows that rapid urease test has higher detection rate than histological examination of the biopsy specimens obtained from the margins of gastric ulcer in diagnosis of H. pylori infection. Under the consideration of the health insurance payments limitation and elimination of false-negative detection rate of H. pylori infection, we strongly recommend the rapid urease test from the antrum and body specimens rather than from the ulcer margins for detection of the bacteria in patients with gastric ulcer disease.

Adult↗
PubMed2006

[Urease test of the gastric content deposits for diagnosis of Helicobacter pylori infection in the gastric mucosa].

A rapid urease test was applied to the examination of the deposit of gastric juice for diagnosing H. pylori in the gastric mucosa. Two hundred and twenty patients blindly randomized were examined in a case control study. The standard rapid urease test kit Jatrox-H.p.-Test (Rohm Pharma, Germany) was used to determine urease activity in the deposit of gastric juice and duodenal [n = 110 (Group 1)] and gastroduodenal [n = 110 (Group 2)] mucosae. Giemsa staining was employed as a comparison method to examine H. pylori infection in the gastric and duodenal mucosae. The availability of regions of duodenal metaplasia was confirmed by periodic acid-Schiff and alcian blue (Serva) staining tests (pH 1.0 and 2.5, respectively). The results of evaluation of the efficiency of the rapid urease test of gastric juice deposit and gastric and duodenal mucosae in Groups 1 and 2 were as follows: sensitivity (SE) (0.97, 0.99, 0,96), specificity (SP) (0.97, 0.97, 0.99), prevalence (0.64, 0.67, 0.24), test accuracy (TA) (0.96, 0.98, 0.98), negative (0.95, 0.97, 0.99) and positive (0.98, 0.99, 0.96) predictive values; positive (38.8, 33.0, 96.0) and negative (0.03, 0.01, 0.04) likelihood ratios. It is expedient to employ the rapid urease test for the diagnosis of H. pylori infection in the stomach (Se 96-99%, Sp 97%, TA 97-98%). When the test of gastric juice deposit and gastric biopsy is positive, the probability of gastric H. pylori availability is 98-99%. When the test is negative (the probability of H. pylori absence is 95-97%), duodenal biopsy is made. When the test of duodenal biopsy is positive, the probability of H. pylori availability is 96%. When it is negative, the probability of H. pylori absence is 99%. An algorithm of use of the rapid urease test to diagnose H. pylori in different intestinal parts (stomach, duodenum) has been developed.

Adult↗
PubMed2006

Comparative study on a homemade rapid urease test with gastric biopsy for diagnosis of Helicobacter pylori infection.

The main objective of this study was to determine whether a homemade rapid urease test was reliable when compared to histology in the diagnosis of Helicobacter pylori infection. Endoscopic antral biopsies from 15th August 2004 to 15th July 2005 were studied prospectively. Rapid urease test and histological examination were done on all specimens. Among 160 biopsies, 56 cases showed H. pylori in histological section and 59 cases were rapid urease test positive. Among 56 H. pylori infected patients, the sensitivity, specificity, positive and negative predictive values, percentage of false positive, and percentage of false negative values of rapid urease test were 96.4%, 95.2%, 91.5%, 98.0%, 4.8% and 3.5% respectively. Rapid urease test is positive in significantly higher number (p < 0.001) in histological positive cases. In conclusion our homemade rapid urease test is a test with good sensitivity and specificity for detection of H. pylori infection.

Adult↗
PubMed1975

[Carbohydrate containing media for the detection of urease in "Klebsiella"].

Sone strains of Klebsiella pneumoniae and K. oxytoca grown on nutrient agar may appear "urease negative" in a Ferguson type reagent medium after a 24 h incubation at 37 degrees C. Amongst such 147 so called urease negative strains, urease has been detected within a few hours in 79 strains, when bacteria have grown on media containing carbohydrates (Kligler iron agar, Drigalski lactose agar, SS agar and Worfel-Ferguson sucrose medium). Acid production by carbohydrate fermentation increases urease production by Klebsiella: pH 4 is the most convenient pH for urease synthesis by these bacteria. The other 68 strains have been considered as urease-less Klebsiella. The best results are obtained from culture on Worfel-Ferguson sucrose medium: urea hydrolysis is positive--on an average-after 1 hour and 30 minutes when detected in a Ferguson type reagent medium, and after 2 hours and 35 minutes when detected in a Christensen reagent medium.

Bacteriological Techniques↗
PubMed1986

Purification of a nickel-containing urease from the rumen anaerobe Selenomonas ruminantium.

Urease was purified 592-fold to homogeneity from the anaerobic rumen bacterium Selenomonas ruminantium. The urease isolation procedure included a heat step and ion-exchange, hydrophobic, gel filtration, and fast protein liquid chromatography. The purified enzyme exhibited a Km for urea of 2.2 +/- 0.5 mM and a Vmax of 1100 mumol of urea min-1 mg-1. The molecular mass estimated for the native enzyme was 360,000 +/- 50,000 daltons, whereas a subunit value of 70,000 +/- 2,000 daltons was determined. These results are in contrast to the findings of Mahadevan et al. (Mahadevan, S., Sauer, F. D., and Erfle, J. D. (1977) Biochem. J. 163, 495-501) in which isolated rumen urease was reported to be one-third this size (Mr 120,000-130,000) and to catalyze urea hydrolysis at a maximum velocity of only 53 mumol min-1 mg-1. S. ruminantium urease contained 2.1 +/- 0.4 nickel ions/subunit, comparable to the nickel content in jack bean urease (Dixon, N.E., Gazzola, C., Blakeley, R.L., and Zerner, B. (1975) J. Am. Chem. Soc. 97, 4131-4133). Thus, the active site of bacterial urease is very similar to that found in the plant enzymes.

Anaerobiosis↗
PubMed1983

Rapid presumptive identification of the Mycobacterium tuberculosis-bovis complex by radiometric determination of heat stable urease.

Simple and rapid Bactec methodologies for the determination of neat (unaltered) and heat stable urease activity of mycobacteria are presented. Clinical isolates (63) and stock cultures (32)--consisting of: M. tuberculosis (19), M. bovis (5), M. kansasii (15), M. marinum (4), M. simiae (3), M. scrofulaceum (16), M. gordonae (6), M. szulgai (6), M. flavescens (1), M. gastri (1), M. intracellulare (6), M. fortuitum-chelonei complex (12), and M. smegmatis (1)--were tested for neat urease activity by Bactec radiometry. Mycobacterial isolates (50-100 mg wet weight) were incubated at 35 degrees C for 30 minutes with microCi14C-urea. Urease-positive mycobacteria gave Bactec growth index (GI) values greater than 100 units, whereas urease-negative species gave values less than 10 GI units. Eighty-three isolates possessing neat urease activity were heated at 80 degrees C for 30 minutes followed by incubation at 35 degrees C for 30 minutes with 1 microCi14C-urea. Mycobacterium tuberculosis-bovis complex demonstrated heat-stable urease activity (GI more than 130 units) and could be distinguished from mycobacteria other than tuberculosis (MOTT), which gave GI values equal to or less than 40 units.

Drug Stability↗
PubMedDate not supplied

[Urease biosynthesis and isolation in Staphylococcus saprophyticus L-1].

Experiments were carried out to investigate the effect of organic components of the medium and cultivation conditions on the multiplication rate and urease biosynthesis by Staphylococcus saprophyticus L-1 cells isolated from natural sources. The yeast enzymic hydrolyzate and corn extract were found to be an adequate substitute for the costly organic components--peptone and yeast extract. The substitutes ensured a high level of urease biosynthesis and biomass accumulation. The biomass accumulation was maximum at pH 6.0-7.0 and the urease activity reached maximum at pH 6.0-6.5. The optimum temperature of cultivation was 37 degrees C. Enhanced aeration and constant pH during microbial cultivation in 250 1 fermenters did not increase the biomass accumulation or urease biosynthesis as compared to flask cultivation. The study of urease isolation from the cell extract showed that the ratio of 3 volumes of ethanol to 1 volume of homogenate was optimum and provided the best precipitation of the enzyme. Preliminary thermal treatment of the cell extract increased the urease activity by 2.5 times. In this situation the activity yield was close to 100%.

Culture Media↗
PubMed1993

[An urease enzyme linked immunosorbent assay for detection of Helicobacter pylori infection].

A sensitive and specific serological diagnostic test for Helicobacter pylori infection has been developed and validated in 120 patients with dyspeptic symptoms undergoing endoscopy. This test is to use urease, a protein unique to H. pylori, as the basis for the enzyme linked immunosorbent assay (ELISA) that detects serum H. pylori urease antibodies. The ELISA mean optical density (OD) in H. pylori-positive group is higher than that in H. pylori-negative group (0.57 +/- 0.23 vs 0.24 +/- 0.15, P < 0.001), a cut-off 0.3 OD yields a sensitivity of 95% and a specificity of 93%. Serum absorption test showed that Escherichia coli, Klebsiella pneumonia, Proteus mirabilis, Yersinia enterocolotica, Pseudomonas aeruginosa cell lysate do not influence serum H. pylori urease antibody level, though they all have urease except E. coli. The result implied that H. pylori urease can be a good antigen to detect serum H. pylori antibody and it would be useful for epidemiological survey and routine diagnostic approach. Nearly half of the blood donors showed positive result with H. pylori urease antibody. It is suggested that H. pylori infection is quite common in the asymptomatic population.

Adult↗
PubMed1993

[The diagnostic accuracy of gastric urease activity for Helicobacter pylori].

The diagnostic accuracy of gastric urease activity for Helicobacter pylori (HP) infection were studied in 98 patients with peptic ulcer, gastritis and chronic renal failure. Gastric aspirates were analyzed for urea nitrogen and ammonia. Urease activity was calculated as the ratio of gastric ammonia to sum of gastric urea nitrogen and ammonia. Gold standard assessments to HP infection were rapid urease test, histology and/or culture. The results showed that the values of urease activity in patients with HP infection higher than that in patients without HP infection. This were further assessed by eradication of HP. Sixteen patients with HP infection were treated with DeNol 330 mg/day for 4 weeks. HP was eradicated in 8/16 patients. In those cases urease activity reduced (P < 0.05). If taken 0.31 as the cut-off index of urease activity to diagnosis HP infection, the sensitivity, specificity and accuracy were 95%, 84%, 93% respectively and were not affected by blood urea nitrogen.

Adolescent↗
PubMed1995

Adaptive cytoprotection by ammonia and urea-urease system in the rat gastric mucosa.

Urease and ammonia (NH4OH) have been proposed to be play a major role in the pathogenesis of the the Helicobacter pylori (Hp)-associated gastric damage but the mechanism of this damage has not been fully explained. This study was designed the determine whether topical application with NH4OH at low concentration or the generation of the NH4OH in gastric lumen by the hydrolysis of urea in the presence of urease can induce adaptive cytoprotection. Single insult of NH4OH alone in various concentrations (15-500 mM) caused the mucosal damage starting at 30 mM and reaching at 250 mM the value similar to that obtained with 100% ethanol and being accompanied by the fall in gastric blood flow to about 30% of the normal value. When the mucosa was first exposed to the low concentration (15 mM) of NH4OH, causing by itself only small microscopic damage of surface epithelium, but then insulted by a high concentration (250 mM) of NH4OH, the extent of mucosal damage was greatly attenuated as compared to that caused by NH4OH alone. This "adaptive" cytoprotection, accompanied by the rise in the GBF, was reversed in part, after the pretreatment with indomethacin to inhibit PG-cyclooxygenase, with L-NAME to suppress NO-synthase or with capsaicin to induce deactivation of sensory nerves. The combined topical pretreatment with urea (2%) and urease (100 U) to generate NH4OH in the stomach, also significantly reduced the severity of gastric lesions induced by 100% ethanol and this was also accompanied by a significant rise in the gastric blood flow. The protective and hyperemic effects of urea and urease were significantly attenuated by the pretreatment with indomethacin or suppression of NO-synthase by L-NAME. The functional ablation of sensory nerves by the pretreatment with capsaicin also reversed, in part, the protective effect of the combination of urea plus urease and abolished completely the mucosal hyperemia accompanying this protection. We conclude that 1) NH4OH alone at higher concentrations damages the gastric mucosa but when applied at lower concentration corresponding to that in the stomach of Hp-infected patients, or generated by the urea in the presence of urease, NH4OH acts like "mild irritant" to induce adaptive cytoprotection, 2) this adaptive cytoprotection is mediated, in part, by endogenous PG, sensory nerves and arginine-NO-dependent pathway.

Adaptation, Physiological↗
PubMed1996

Urea-urease system in cytoprotection against acute mucosal damage.

Ammonia (NH4OH) generated by urease from urea in the Helicobacter pylori (Hp)-infected stomach is considered as a one of the major pathogenic factors in the Hp-associated gastritis but the mechanism of the deleterious action of NH4OH on gastric mucosa has not been fully explained. In this study, the gastric mucosa was exposed to topical NH4OH in various concentrations (15-250 mM) (series A) and to NH4OH in a small concentration followed by a high concentration (250 mM) of NH4OH (series B) or to the combination of urea and urease to generate NH4OH (series C) followed by 250 mM NH4OH in order to determine the "mild irritant" and protective properties of this substance on the mucosa. Administration of NH4OH alone resulted in a concentration-dependent mucosal damage starting at 30 mM and reaching at 250 mM the degree similar to that obtained with 100% ethanol. The acute mucosal damage by NH4OH was accompanied by the fall in gastric blood flow reaching nadir at 250 mM NH4OH of about 30% of the normal value. When the mucosa was first exposed to low concentration of NH4OH (15 mM) and then insulted with its larger concentration (250 mM), the lesion area was markedly reduced as compared to that obtained with 250 mM NH4OH alone and this effect was accompanied by a significant rise in the GBF. This adaptive cytoprotection by 15 mM NH4OH was reversed, in part, by the pretreatment with indomethacin to inhibit prostaglandins (PG) or L-NAME to suppress nitric oxide (NO) formation or after capsaicin-induced denervation of sensory nerves. Blockade of endogenous sulfhydryls (SH) by N-ethylmaleimide (NEM) eliminated this adaptive cytoprotection but the suppression of ornithine decarboxylase (ODC), a key enzyme in polyamine biosynthesis, by alpha-difluoro methylornithine (DFMO) failed to influence the protection and accompanying hyperemia afforded by NH4OH in low concentration. The combination of urea (2%) and urease (100 U), which raised the gastric luminal NH4OH concentration by about 5-folds, also reduced significantly the lesions provoked by 250 mM NH4OH. This protection and accompanying hyperemia induced was significantly attenuated by the pretreatment with indomethacin or hydroxyurea, a potent urease inhibitor. Hydroxyurea abolished completely the rise in luminal NH4OH produced by the combined treatment of urea plus urease. We conclude that 1) NH4OH in high concentration damages the gastric mucosa but when applied at lower concentration or generated in the stomach by urea-urease system, acts as local mild irritant to induce adaptive cytoprotection that probably involves PG, sensory nerves and arginine-NO-pathaway.

Ammonium Hydroxide↗
PubMed1995

Urease Is Not Essential for Ureide Degradation in Soybean.

The hypothesis that soybean (Glycine max L. [Merrill]) catabolizes ureides to urea to a physiologically significant extent was tested and rejected. Urease-negative (eu3-e1/eu3-e1) plants were supported by fixed N2 or by 2 mM NH4NO3, so that xylem-borne nitrogen contained predominantly ureides (allantoin and allantoic acid) or amide amino acids, respectively. Seed nitrogen yield was equal on either nitrogen regime, although 35-d-old fixing plants accumulated about 6 times more leaf urea. In callus, lack of an active urease reduced growth on either arginine or allantoin as the sole nitrogen source, but the reduction was greater on arginine (73%) than on allantoin (39%). Furthermore, urease-negative cells accumulated 17 times more urea than urease-positive cells on arginine; for allantoin the ratio was 1.8. Urease-negative callus accumulated urea at 3% the rate of seedlings. To test whether urea accumulating in urease-negative seedlings was derived from ureides, seeds were first allowed to imbibe in 1 mM allopurinol, an inhibitor of ureide formation. Seedling ureides were decreased by 90%, but urea levels were unchanged. Thus, ureides are poor precursors of urea, which was confirmed in seedlings that converted no more than 5% of seed-absorbed [14C-ureido]allantoate to [14C]urea, whereas 40 to 70% of [14C-guanido]arginine was recovered as [14C]urea.

Journal Article↗
PubMed2004

Epitope mapping and features of the epitope for monoclonal antibodies inhibiting enzymatic activity of Helicobacter pylori urease.

Two characteristic monoclonal antibodies (HpU-2 and -18) out of 26 monoclonal antibodies (HpU-1 approximately 26) produced against Helicobacter pylori (H. pylori) urease showed a strong inhibitory effect against the enzymatic activity of the urease. Epitope mapping about some monoclonal antibodies of the HpU-series inhibiting enzymatic activity was performed by using a surface plasmon resonance apparatus and by digesting H. pylori urease with trypsin, followed by mass spectroscopy. The sequences of the epitopes recognized by HpU-2 and -18 were SVELIDIGGNRRIFGFNALVDR (22 mer) and IFGFNALVDR (10 mer), respectively. The former sequence is present as a part of a loop structure at a position close to the C-terminal of the alpha-subunit of H. pylori urease, although it has been suggested that the active site of the urease resides in the beta-subunit. The above peptide (22 mer) was chemically synthesized in a linear and cyclic form, and its conjugate with BSA was immunized in rabbits. The resultant serum induced by the linear form could specifically bind to H. pylori infecting human gastric mucosa. These results suggest that the above sequence (22 mer) must be an important epitope, although it locates in the alpha-subunit but not in the beta-subunit.

Amino Acid Sequence↗
PubMed1992

Biological activity of urease formulated in poloxamer 407 after intraperitoneal injection in the rat.

The advent of genetic engineering has resulted in a proliferation of protein pharmaceuticals available for a variety of therapeutic needs. However, the formulation and delivery of these proteins remain an intriguing challenge. Polymer-based protein drug delivery systems continue to be investigated, although many of the fabrication techniques used to incorporate proteins into the polymer matrix or device result in irreversible inactivation (denaturation) of the proteins. A well-characterized model enzyme, urease, was formulated in 33% (w/w) poloxamer 407 (Pluronic F-127) vehicle and injected intraperitoneally (ip) into rats in an attempt to achieve both preservation of biological activity and sustained release of the protein. The resulting ammonia concentration in plasma-time profiles were compared with those for rats injected with an identical dose (27.6 units of activity per 200 g of body weight) of urease dissolved in pH 7 phosphate buffer. Neither a pH 7 phosphate buffer solution nor poloxamer 407 (33%, w/w) dissolved in pH 7 phosphate buffer, when injected ip into rats, resulted in elevated ammonia levels in plasma. The time to reach a maximum ammonia level in plasma was increased approximately threefold following the injection of the urease-poloxamer 407 formulation, compared with that in control rats administered an identical dose of urease in solution. In addition, hyperammonemia was extended almost threefold in treated rats compared with control rats, without untoward effects. However, prolonged hyperammonemia in animals receiving an ip injection of the urease-poloxamer 407 formulation may have potentially resulted from the reduced clearance of ammonia and ammonium ion in the proximal tubules of the rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Ammonia↗