Fenbendazole as a method for measuring supplement intake in grazing sheep

2012 ◽  
Vol 52 (12) ◽  
pp. 1142 ◽  
Author(s):  
F. J. Fishpool ◽  
L. P. Kahn ◽  
D. J. Tucker ◽  
J. V. Nolan ◽  
R. A. Leng
Keyword(s):  
Dose Rate ◽  
Plasma Concentrations ◽  
Area Under The Curve ◽  
Gastrointestinal Nematode ◽  
Good Representation ◽  
Dose Rates ◽  
Internal Parasites ◽  
Grazing Sheep ◽  
The Relationship ◽  
Supplement Intake

Currently there is a need for an accurate and non-hazardous method to measure individual intake of a supplement in grazing sheep over a prolonged period. This paper examines the potential of fenbendazole (FBZ) as a marker of intake. The following five experiments aim to determine the relationship between oral ingestion of FBZ and the plasma concentrations of FBZ and its metabolites oxfendazole (OFZ) and FBZ-sulfone (SUL) after single, multiple and daily doses both in housed and grazing sheep and sheep infected with internal parasites. The results from these experiments indicate that OFZ+SUL concentrations in plasma are dependent on FBZ dose rate in housed and grazing animals with differences evident between different dose rates (P < 0.001). Variability of OFZ and SUL concentrations increase in grazing compared with housed animals. Area under the curve of metabolite concentrations was also shown to indicate dose rate regardless of the timing and frequency of dose. Stepwise regressions indicated that sampling every 48 h gave a good representation of area under the curve for different dose rates (R2 = 0.951, P < 0.001). A significant separation of treatment means was achieved when samples were taken every 48 h and pooled during daily dosing with FBZ (P < 0.001). Finally gastrointestinal nematode infection did not affect OFZ and SUL concentrations after daily doses of FBZ. The results from these experiments indicate that FBZ is a useful and accurate marker of supplement intake in grazing animals.

Copper oxide particles for grazing sheep

1983 ◽  
Vol 34 (6) ◽  
pp. 751 ◽  
Author(s):  
JP Langlands ◽  
JE Bowles ◽  
GE Donald ◽  
AJ Smith ◽  
DR Paull ◽  
...  
Keyword(s):  
Copper Oxide ◽  
Dose Rate ◽  
Copper Toxicity ◽  
Dose Rates ◽  
Hepatic Copper ◽  
Copper Status ◽  
Oxide Particles ◽  
Grazing Sheep ◽  
Copper Storage ◽  
Rate Of Decline

In a series of experiments aimed at evaluating copper oxide as a supplement, grazing sheep were dosed with varying quantities of copper oxide particles up to 64 g, and the toxicity, the rate of particle excretion, and copper storage in the liver and other tissues were recorded. The toxicities (LD50) of copper oxide particles were 1.17 and 1.80 g/kg liveweight for two groups of grazing adult fine-wool Merino sheep. Death usually occurred 88-96 days after the oral administration of the particles; mean hepatic copper concentrations of sheep dying from copper toxicity were 4122-4308 mg/kg DM. The rate of faecal copper excretion of copper-supplemented sheep, expressed as a percentage of the dose, was less when 50 g of particles were given than when the dose was 5 or 10 g, but excretion patterns were variable. The quantity of hepatic copper stored per g of copper oxide given declined as the dose increased from 0 to 32 g, but increased again at higher doses. Hepatic copper concentration reached a maximum 2-3 months after dosing and the rate of decline was positively related to dose rate; thus, large doses of copper are unlikely to extend the period of elevated copper status. Large doses also increased whole blood copper concentrations and elevated plasma aspartate transaminase activities; this was taken to indicate copper poisoning. Tissue copper concentrations from sheep given up to 64 g particles are reported; liver was the most sensitive to copper treatment. Copper contents of the lung and kidney also responded to copper therapy, but carcass components such as leg, shoulder and muscle did not. Weaned lambs given 2 g of particles (c. 0.13 g/kg liveweight) grew significantly faster than unsupplemented lambs. This dose rate was approximately one-seventh of that predicted to cause 5% mortality, and it is concluded that, at appropriate dose rates, this method of supplementation did not increase mortality or cause excessive increases in tissue copper concentrations, and could increase growth rate.

scholarly journals Conditioned flavour aversions in sheep: the relationship between the dose rate of a secondary plant compound and the acquisition and persistence of aversions

1998 ◽  
Vol 79 (1) ◽  
pp. 55-62 ◽  
Author(s):  
I. Kyriazakis ◽  
D. H. Anderson ◽  
A. J. Duncan
Keyword(s):  
Dose Rate ◽  
Live Weight ◽  
Food Plants ◽  
Short Term ◽  
Novel Foods ◽  
Dose Rates ◽  
Conditioning Period ◽  
The Relationship ◽  
Preference Tests

Within the overall objective of whether ruminants are able to form conditioned aversions (CFA) toward a food flavour associated with the administration of an aversive stimulus which occurs naturally in food plants (oxalic acid, OA), two specific objectives were tested: (1) whether the rate and degree of formation of CFA are dependent on the dose rate of OA administered and (2) whether the persistence of formed CFA depends on the previous dose rate of OA. Sheep were conditioned to associate the specific flavour of one of two novel foods with either the oral administration of OA or equivalent placebos. Four dose rates of OA were tested (0.06, 0.12, 0.18 and 0.24 g/kg sheep live weight per d), with twelve sheep per dose. Each conditioning period lasted for 8 d and was repeated four times. At the end of each conditioning period the preference for the two flavours was measured in short-term, 20min preference tests. The persistence of the CFA was measured at 0, 7, 21 and 49 d after the completion of the conditioning phase with long-term, 3 h preference tests. The results of the experiment indicated that: (1) the rate and degree of formation of CFA were dependent on the rate of administration of OA; (2) sheep required repeated exposures to the lower dose rates of OA in order to develop CFA and these CFA did not persist in the absence of continual reinforcement; (3) CFA to the higher dose rates of OA were developed after as little as one exposure and persisted over a period of at least 7 weeks. These findings are consistent with the expectation that ruminants should be able to select a diet which minimizes the risk of consumption of potentially harmful foods, whilst at the same time maintaining a degree of flexibility in their feeding behaviour.

Design, Synthesis, Anticonvulsant Activity, Preclinical Study and Pharmacokinetic Performance of N-{[3-(4-chlorophenyl)-4-oxo-3, 4-dihydroquinazolin- 2-yl] methyl}, 2-[(2-isopropyl-5-methyl) 1-cyclo Hexylidene] Hydrazinecarboxamide

2019 ◽  
Vol 19 (1) ◽  
pp. 31-45
Author(s):  
Meena K. Yadav ◽  
Laxmi Tripathi
Keyword(s):  
Anticonvulsant Activity ◽  
Computational Study ◽  
Plasma Concentrations ◽  
Elimination Rate ◽  
Area Under The Curve ◽  
Preclinical Study ◽  
In Vivo Studies ◽  
Maximum Plasma ◽  
Seizure Models

Background: N-{[3-(4-chlorophenyl)-4-oxo-3, 4-dihydroquinazolin-2-yl] methyl}, 2-[(2- isopropyl-5-methyl) 1-cyclohexylidene] hydrazinecarboxamide QS11 was designed by computational study. It possessed essential pharmacophoric features for anticonvulsant activity and showed good docking with iGluRs (Kainate) glutamate receptor. Methods: QSAR and ADMET screening results suggested that QS11 would possess good potency for anticonvulsant activity. QS11 was synthesised and evaluated for its anticonvulsant activity and neurotoxicity. QS11 showed protection in strychnine, thiosemicarbazide, 4-aminopyridine and scPTZ induced seizure models and MES seizure model. QS11 showed higher ED50, TD50 and PI values as compared to the standard drugs in both MES and scPTZ screen. A high safety profile (HD50/ED50 values) was noted and hypnosis, analgesia, and anaesthesia were only observed at higher doses. No considerable increase or decrease in the concentration of liver enzymes was observed. Optimized QS11 was subjected to preclinical (in-vivo) studies and the pharmacokinetic performance of the sample was investigated. The result revealed that the pharmacokinetic performance of QS11 achieved maximum plasma concentrations (Cmax) of 0.315 ± 0.011 µg/mL at Tmax of 2.0 ± 0.13 h, area under the curve (AUC0-∞) value 4.591 ± 0.163 µg/ml x h, elimination half-life (T1/2) 6.28 ± 0.71 h and elimination rate constant was found 0.110 ± 0.013 h-1. Results and Conclusion: Above evidences indicate that QS11 could serve as a lead for development of new antiepileptic drugs.

Ascertaining an efficient eligibility cut-off for extended Medicare items for eating disorders

2021 ◽  
pp. 103985622110286
Author(s):  
Tracey Wade ◽  
Jamie-Lee Pennesi ◽  
Yuan Zhou
Keyword(s):  
Eating Disorders ◽  
Eating Disorder ◽  
False Positive Rate ◽  
Area Under The Curve ◽  
Rate Sensitivity ◽  
True Positive Rate ◽  
Eating Disorder Examination Questionnaire ◽  
Eating Disorder Examination ◽  
Positive Rate ◽  
The Relationship

Objective: Currently eligibility for expanded Medicare items for eating disorders (excluding anorexia nervosa) require a score ⩾ 3 on the 22-item Eating Disorder Examination-Questionnaire (EDE-Q). We compared these EDE-Q “cases” with continuous scores on a validated 7-item version of the EDE-Q (EDE-Q7) to identify an EDE-Q7 cut-off commensurate to 3 on the EDE-Q. Methods: We utilised EDE-Q scores of female university students ( N = 337) at risk of developing an eating disorder. We used a receiver operating characteristic (ROC) curve to assess the relationship between the true-positive rate (sensitivity) and the false-positive rate (1-specificity) of cases ⩾ 3. Results: The area under the curve showed outstanding discrimination of 0.94 (95% CI: .92–.97). We examined two specific cut-off points on the EDE-Q7, which included 100% and 87% of true cases, respectively. Conclusion: Given the EDE-Q cut-off for Medicare is used in conjunction with other criteria, we suggest using the more permissive EDE-Q7 cut-off (⩾2.5) to replace use of the EDE-Q cut-off (⩾3) in eligibility assessments.

Comparing the Effects of Immersed Versus Land-Based High-Intensity Interval Cycling on Energy Intake, Appetite Sensations and Perceived Exertion Among Healthy Men

2021 ◽  
pp. 003151252110073
Author(s):  
Lore Metz ◽  
Laurie Isacco ◽  
Maud Miguet ◽  
Pauline Genin ◽  
David Thivel ◽  
...  
Keyword(s):  
Energy Intake ◽  
High Intensity ◽  
Perceived Exertion ◽  
Area Under The Curve ◽  
Macronutrient Intake ◽  
Healthy Men ◽  
High Intensity Interval ◽  
Interval Cycling ◽  
Desire To Eat ◽  
The Relationship

Immersed exercise has been shown to induce higher energy expenditure and no difference or increase in food intake compared with similar exercise on land. In this study, we compared the effects of acute high-intensity cycling performed on land versus when immersed on subsequent energy intake (EI), appetite sensations and perceived exertion (RPE) in healthy men. Ten participants in a postprandial condition completed three experimental visits in a randomized order: a control condition (CONT); a high-intensity interval cycling exercise performed on land (HIIE-L) and the same exercise while immersed in water (HIIE-A) with a similar targeted heart rate. We observed no difference in energy and macronutrient intake and in area under the curve (AUC) for appetite sensations between sessions. The RPE at the end of HIIE-L was negatively correlated with EI (r=–0.67; p < 0.05), AUC for hunger (r=–0.86, p < 0.01), desire to eat (r=–0.78, p < 0.05) and prospective food consumption (r=–0.86, p < 0.01). Conversely, the RPE at the end of HIIE-L was positively correlated with AUC for fullness (r = 0.76 , p < 0.05). No such correlations were observed for HIIE-A. The present study was the first to observe that immersion did not influence EI after HIIE cycling, but immersion blunted the relationship between session RPE and subsequent energy intake and appetite sensations relative to HIIE on land.

scholarly journals Physiologically Based Pharmacokinetic Modelling of Cabozantinib to Simulate Enterohepatic Recirculation, Drug–Drug Interaction with Rifampin and Liver Impairment

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 778
Author(s):  
Bettina Gerner ◽  
Oliver Scherf-Clavel
Keyword(s):  
Hepatic Impairment ◽  
Kinase Inhibitor ◽  
Plasma Concentrations ◽  
Area Under The Curve ◽  
Enterohepatic Recirculation ◽  
Maximum Plasma ◽  
Good Precision ◽  
Physiologically Based Pharmacokinetic ◽  
Starting Point ◽  
Physiologically Based

Cabozantinib (CAB) is a receptor tyrosine kinase inhibitor approved for the treatment of several cancer types. Enterohepatic recirculation (EHC) of the substance is assumed but has not been further investigated yet. CAB is mainly metabolized via CYP3A4 and is susceptible for drug–drug interactions (DDI). The goal of this work was to develop a physiologically based pharmacokinetic (PBPK) model to investigate EHC, to simulate DDI with Rifampin and to simulate subjects with hepatic impairment. The model was established using PK-Sim® and six human clinical studies. The inclusion of an EHC process into the model led to the most accurate description of the pharmacokinetic behavior of CAB. The model was able to predict plasma concentrations with low bias and good precision. Ninety-seven percent of all simulated plasma concentrations fell within 2-fold of the corresponding concentration observed. Maximum plasma concentration (Cmax) and area under the curve (AUC) were predicted correctly (predicted/observed ratio of 0.9–1.2 for AUC and 0.8–1.1 for Cmax). DDI with Rifampin led to a reduction in predicted AUC by 77%. Several physiological parameters were adapted to simulate hepatic impairment correctly. This is the first CAB model used to simulate DDI with Rifampin and hepatic impairment including EHC, which can serve as a starting point for further simulations with regard to special populations.

scholarly journals Snoring: a source of noise pollution and sleep apnea predictor

SLEEP ◽  
2019 ◽  
Vol 43 (6) ◽  
Author(s):  
Mudiaga Sowho ◽  
Francis Sgambati ◽  
Michelle Guzman ◽  
Hartmut Schneider ◽  
Alan Schwartz
Keyword(s):  
Sleep Apnea ◽  
Operating Characteristic ◽  
Area Under The Curve ◽  
Noise Pollution ◽  
Apnea Hypopnea Index ◽  
Sleep Study ◽  
Sound Levels ◽  
Obstructive Sleep ◽  
Single Night ◽  
The Relationship

Abstract Snoring is a highly prevalent condition associated with obstructive sleep apnea (OSA) and sleep disturbance in bed partners. Objective measurements of snoring in the community, however, are limited. The present study was designed to measure sound levels produced by self-reported habitual snorers in a single night. Snorers were excluded if they reported nocturnal gasping or had severe obesity (BMI &gt; 35 kg/m2). Sound was measured by a monitor mounted 65 cm over the head of the bed on an overnight sleep study. Snoring was defined as sound ≥40 dB(A) during flow limited inspirations. The apnea hypopnea index (AHI) and breath-by-breath peak decibel levels were measured. Snore breaths were tallied to determine the frequency and intensity of snoring. Regression models were used to determine the relationship between objective measures of snoring and OSA (AHI ≥ 5 events/h). The area under the curve (AUC) for the receiver operating characteristic (ROC) was used to predict OSA. Snoring intensity exceeded 45 dB(A) in 66% of the 162 participants studied, with 14% surpassing the 53 dB(A) threshold for noise pollution. Snoring intensity and frequency were independent predictors of OSA. AUCs for snoring intensity and frequency were 77% and 81%, respectively, and increased to 87% and 89%, respectively, with the addition of age and sex as predictors. Snoring represents a source of noise pollution in the bedroom and constitutes an important target for mitigating sound and its adverse effects on bed partners. Precise breath-by-breath identification and quantification of snoring also offers a way to risk stratify otherwise healthy snorers for OSA.

scholarly journals Radiation Awareness for Endovascular Abdominal Aortic Aneurysm Repair in the Hybrid Operating Room: An Instant Operator Risk Chart for Daily Practice

2021 ◽  
pp. 152660282110074
Author(s):  
Quirina M. B. de Ruiter ◽  
Frans L. Moll ◽  
Constantijn E. V. B. Hazenberg ◽  
Joost A. van Herwaarden
Keyword(s):  
Radiation Dose ◽  
Dose Rate ◽  
Effect Size ◽  
Radiation Risk ◽  
Dose Limit ◽  
Access Site ◽  
Femoral Access ◽  
Dose Rates ◽  
Rate Prediction ◽  
Operator Dose

Introduction: While the operator radiation dose rates are correlated to patient radiation dose rates, discrepancies may exist in the effect size of each individual radiation dose predictors. An operator dose rate prediction model was developed, compared with the patient dose rate prediction model, and converted to an instant operator risk chart. Materials and Methods: The radiation dose rates (DRoperator for the operator and DRpatient for the patient) from 12,865 abdomen X-ray acquisitions were selected from 50 unique patients undergoing standard or complex endovascular aortic repair (EVAR) in the hybrid operating room with a fixed C-arm. The radiation dose rates were analyzed using a log-linear multivariable mixed model (with the patient as the random effect) and incorporated varying (patient and C-arm) radiation dose predictors combined with the vascular access site. The operator dose rate models were used to predict the expected radiation exposure duration until an operator may be at risk to reach the 20 mSv year dose limit. The dose rate prediction models were translated into an instant operator radiation risk chart. Results: In the multivariate patient and operator fluoroscopy dose rate models, lower DRoperator than DRpatient effect size was found for radiation protocol (2.06 for patient vs 1.4 for operator changing from low to medium protocol) and C-arm angulation. Comparable effect sizes for both DRoperator and DRpatient were found for body mass index (1.25 for patient and 1.27 for the operator) and irradiated field. A higher effect size for the DRoperator than DRpatient was found for C-arm rotation (1.24 for the patient vs 1.69 for the operator) and exchanging from femoral access site to brachial access (1.05 for patient vs 2.5 for the operator). Operators may reach their yearly 20 mSv year dose limit after 941 minutes from the femoral access vs 358 minutes of digital subtraction angiography radiation from the brachial access. Conclusion: The operator dose rates were correlated to patient dose rate; however, C-arm angulation and changing from femoral to brachial vascular access site may disproportionally increase the operator radiation risk compared with the patient radiation risk. An instant risk chart may improve operator dose awareness during EVAR.

scholarly journals Relationship between Plasma Trimethylamine N-Oxide Levels and Renal Dysfunction in Patients with Hypertension

2021 ◽  
pp. 1-12
Author(s):  
Jia Zhou ◽  
Dingkun Wang ◽  
Bingong Li ◽  
Xuelian Li ◽  
Xingjun Lai ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Kidney Disease ◽  
Renal Dysfunction ◽  
High Performance ◽  
Characteristic Curve ◽  
Area Under The Curve ◽  
Hypertensive Patients ◽  
Ckd Stage ◽  
Liquid Chromatography Tandem Mass ◽  
The Relationship

<b><i>Introduction:</i></b> Trimethylamine N-oxide (TMAO) is a metabolite produced by gut bacteria. Although increased TMAO levels have been linked to hypertension (HTN) and chronic kidney disease (CKD) with poor prognosis, no clinical studies have directly addressed the relationship between them. In this study, we investigated the relationship between TMAO and renal dysfunction in hypertensive patients. <b><i>Methods:</i></b> We included healthy controls (<i>n</i> = 50), hypertensive patients (<i>n</i> = 46), and hypertensive patients with renal dysfunction (<i>n</i> = 143). Their blood pressure values were taken as the highest measured blood pressure. Renal function was evaluated using the estimated glomerular filtration rate. Plasma TMAO levels were measured using high-performance liquid chromatography tandem mass spectrometry. <b><i>Results:</i></b> We found significant differences in plasma TMAO levels among the 3 groups (<i>p</i> &#x3c; 0.01). The plasma TMAO of patients with HTN was significantly higher than that of healthy people, and the plasma TMAO of patients with HTN complicated by renal dysfunction was significantly higher than either of the other groups. Patients in the highest TMAO quartile were at a higher risk of developing CKD stage 5 than those in the lowest quartile. In the receiver operating characteristic curve, the area under the curve of TMAO combined with β 2-macroglobulin for predicting renal dysfunction in patients with HTN was 0.85 (95% confidence interval 0.80–0.90). <b><i>Conclusion:</i></b> An elevated TMAO level reflects higher levels of HTN and more severe renal dysfunction. TMAO, combined with β 2-macroglobulin levels, may assist in diagnosing CKD in hypertensive patients. Plasma TMAO has predictive value for early kidney disease in hypertensive patients.

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