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    Comparison of the effects of 7.2% hypertonic saline and 20% mannitol on electrolyte and acid-base variables in dogs with suspected intracranial hypertension
    (Wiley Periodicals LLC. on behalf of the American College of Veterinary Internal Medicine, 2021-01-31) Hoehne SN; Yozova ID; Vodondo B; Adamik KN
    Background Hyperosmolar agents frequently are used to decrease intracranial pressure but their effects on electrolyte and acid-base variables have not been prospectively investigated. Objectives Compare duration and magnitude of changes in electrolyte and acid-base variables after hyperosmolar treatment. Animals Twenty-eight client-owned dogs with intracranial hypertension caused by various pathologies. Methods Prospective, randomized, nonblinded, experimental cohort study. Fifteen dogs received a single dose (4 mL/kg) of 7.2% hypertonic saline (HTS), 13 dogs received 20% mannitol (MAN) 1 g/kg IV. Electrolyte and acid-base variables were measured before (T0), and 5 (T5), 60 (T60), and 120 (T120) minutes after administration. Variables were compared between treatments and among time points within treatment groups. Results Mean plasma sodium and chloride concentrations were higher after HTS than MAN at T5 (158 vs 141 mEq/L; 126 vs 109 mEq/L) and significant differences were maintained at all time points. After HTS, plasma sodium and chloride concentrations remained increased from T0 at all time points. After MAN, plasma sodium and chloride concentrations decreased at T5, but these changes were not maintained at T60 and T120. Plasma potassium concentration was lower at T5 after HTS compared with T0 (3.6 vs 3.9 mEq/L) and compared to MAN (3.6 vs 4.1 mEq/L). At T60 and T120, plasma ionized calcium concentration was lower after HTS than MAN (1.2 vs 1.3 mmol/L). No significant differences were found in acid-base variables between treatments. Conclusions and Clinical Importance At the administered dose, dogs receiving HTS showed sustained increases in plasma sodium and chloride concentrations, whereas dogs receiving MAN showed transient decreases. Future studies should assess the effects of multiple doses of hyperosmolar agents on electrolyte and acid-base variables.
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    A Simple, Robust, and Convenient HPLC Assay for Urinary Lactulose and Mannitol in the Dual Sugar Absorption Test
    (MDPI (Basel, Switzerland), 2022-05) Sequeira IR; Kruger MC; Hurst RD; Lentle RG; Locatelli M
    BACKGROUND: Heterogeneous laborious analytical methodologies for the determination of urinary lactulose and mannitol limit their utility in intestinal permeability testing. METHODS: We developed an assay using a Shimadzu HPLC system, an Aminex HPX87C column, and refractive index detection. The test was calibrated using a series of dilutions from standard stock solutions of lactulose and mannitol 'spiked' into urine samples. The utility to quantify urinary excretion during the dual sugar absorption test over 6 h was also determined. RESULTS: Lactulose and mannitol were eluted isocratically at 5.7 and 10.1 min, respectively, with water as a mobile phase at a flow rate of 0.3 mL min-1, 858 psi, 60 °C. The calibration curves for both sugars were linear up to 500 µg mL-1 with a limit of detection in standard solutions at 4 µg mL-1 and in 'spiked' urine samples at 15 µg mL-1. The intra-assay and inter-assay CVs were between 2.0-5.1% and 2.0-5.1% for lactulose and 2.5-4.4% and 2.8-3.9% for mannitol. The urinary profiles of the 6 h absorption of lactulose and mannitol showed similar peak-retention times to standard solutions and were well-resolved at 5.9 and 10.4 min, respectively. CONCLUSIONS: The assay was easy to automate, using commonly available equipment and convenient requiring no prior laborious sample derivatization. The simplicity, reproducibility, and robustness of this assay facilitates its use in routine clinical settings for the quantification of intestinal permeability.
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    The aspirin augmented standardized lactulose mannitol test as a measure of the 'health' of the gastrointestinal tract : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy at Massey University, Palmerston North, New Zealand
    (Massey University, 2015) Sequeira, Ivana Roosevelt
    In this thesis, I studied the ‘classical’ lactulose mannitol test for intestinal permeability that has been used to measure the integrity of the intestinal mucosa and thus to provide an index of recovery from inflammatory bowel disease (IBD) and from autoimmune diseases such as coeliac disease. Perusal of the literature indicates that the protocol for the test has not been standardized and a variety of different test protocols have been used. Hence there are differences in the duration of urinary sampling, the doses of the two test probes, the volumes of fluid consumed during the test and the administration of the test during the fasted or fed state. There is therefore a need for a standardized test. The bulk of the research conducted in this thesis was to develop an optimal protocol with a standardized osmolarity (720 osmol l-1) for the test solution that contained 10 g of lactulose and 5 g of mannitol dissolved in 100 ml of water. Similarly the total fluid intake was standardized to 700 ml. The volumes of fluid consumed over the experimental period were also standardized in order to control for any osmolar effects of the test drink and to hydrate the subjects sufficiently to enable them to produce half-hourly urine samples of a reasonable volume. The rates of excretion and the timings of the peaks in the excretion of mannitol and lactulose were found to vary over time in healthy subjects. Hence the rate of mannitol excretion peaked during the first two hrs whilst the rate of lactulose excretion peaked at four hrs. The correlation between urinary excretion with intestinal transit times were confirmed using a wireless motility capsule. The work with the wireless motility capsule indicated that the probe sugars were in the small intestine from 2½ - 4 hrs and in the proximal colon from 4½ - 6 hrs following dosage with the test solution. Hence a sample collected during the 2½ - 4 hr period is best for assessing permeability of the small intestinal mucosa in healthy subjects. The wireless motility capsule also confirmed that the standardized dose of the lactulose mannitol did not influence gastric transit time or that through the small intestine and large intestine. These findings confirmed that the standardized test was determining absorption during transit of the test sugars through the small and the large intestine. The effect of co-dosage with 600 mg of aspirin in the standardized test was then examined as a means of assessing the effect of a reproducible noxious stimulus on the absorption of the sugar probes. This agent augmented small intestinal permeability to lactulose and decreased its permeability to mannitol. Furthermore dosage with aspirin amplified the effect of a pre-existing adverse stimulus such as smoking. Hence the aspirin augmented test could conceivably be used to ‘unearth’ sub-clinical inflammation. Further work explored the effect of an antioxidant, ascorbic acid, on mucosal permeability. The results showed that, rather than mitigating the adverse effects of aspirin, ascorbic acid augmented intestinal permeability. In summary the work in this thesis has enabled the development of a standardized test that optimizes the ability of the lactulose mannitol test to detect clinical disorders of absorption. Further, augmenting the test with a single dose of aspirin may be useful as an index of gut health or robustness.
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    Comparison of the effects of 7.2% hypertonic saline and 20% mannitol on whole blood coagulation and platelet function in dogs with suspected intracranial hypertension - a pilot study
    (BioMed Central, 19/06/2017) Yozova ID; Howard J; Henke D; Dirkmann D; Adamik KN
    Hyperosmolar therapy with either mannitol or hypertonic saline (HTS) is commonly used in the treatment of intracranial hypertension (ICH). In vitro data indicate that both mannitol and HTS affect coagulation and platelet function in dogs. The aim of this study was to compare the effects of 20% mannitol and 7.2% HTS on whole blood coagulation using rotational thromboelastometry (ROTEM®) and platelet function using a platelet function analyzer (PFA®) in dogs with suspected ICH. Thirty client-owned dogs with suspected ICH needing osmotherapy were randomized to receive either 20% mannitol (5 ml/kg IV over 15 min) or 7.2% HTS (4 ml/kg IV over 5 min). ROTEM® (EXTEM® and FIBTEM® assays) and PFA® analyses (collagen/ADP cartridges) were performed before (T0), as well as 5 (T5), 60 (T60) and 120 (T120) minutes after administration of HTS or mannitol. Data at T5, T60 and T120 were analyzed as a percentage of values at T0 for comparison between groups, and as absolute values for comparison between time points, respectively.No significant difference was found between the groups for the percentage change of any parameter at any time point except for FIBTEM® clotting time. Within each group, no significant difference was found between time points for any parameter except for FIBTEM® clotting time in the HTS group, and EXTEM® and FIBTEM® maximum clot firmness in the mannitol group. Median ROTEM® values lay within institutional reference intervals in both groups at all time points, whereas median PFA® values were above the reference intervals at T5 (both groups) and T60 (HTS group).Using currently recommended doses, mannitol and HTS do not differ in their effects on whole blood coagulation and platelet function in dogs with suspected ICH. Moreover, no relevant impairment of whole blood coagulation was found following treatment with either solution, whereas a short-lived impairment of platelet function was found after both solutions.