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- Ekstrand, Carl, et al.
(författare)
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A quantitative approach to analysing cortisol response in the horse
- 2016
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Ingår i: Journal of Veterinary Pharmacology and Therapeutics. - : Wiley. - 0140-7783 .- 1365-2885. ; 39:3, s. 255-263
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Tidskriftsartikel (refereegranskat)abstract
- The cortisol response to glucocorticoid intervention has, in spite of several studies in horses, not been fully characterized with regard to the determinants of onset, intensity and duration of response. Therefore, dexamethasone and cortisol response data were collected in a study applying a constant rate infusion regimen of dexamethasone (0.17, 1.7 and 17g/kg) to six Standardbreds. Plasma was analysed for dexamethasone and cortisol concentrations using UHPLC-MS/MS. Dexamethasone displayed linear kinetics within the concentration range studied. A turnover model of oscillatory behaviour accurately mimicked cortisol data. The mean baseline concentration range was 34-57g/L, the fractional turnover rate 0.47-1.5 1/h, the amplitude parameter 6.8-24g/L, the maximum inhibitory capacity 0.77-0.97, the drug potency 6-65ng/L and the sigmoidicity factor 0.7-30. This analysis provided a better understanding of the time course of the cortisol response in horses. This includes baseline variability within and between horses and determinants of the equilibrium concentration-response relationship. The analysis also challenged a protocol for a dexamethasone suppression test design and indicated future improvement to increase the predictability of the test.
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| 5. |
- Ekstrand, Carl, et al.
(författare)
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Plasma concentration-dependent suppression of endogenous hydrocortisone in the horse after intramuscular administration of dexamethasone-21-isonicotinate
- 2015
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Ingår i: Journal of Veterinary Pharmacology and Therapeutics. - : Wiley. - 0140-7783 .- 1365-2885. ; 38:3, s. 235-242
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Tidskriftsartikel (refereegranskat)abstract
- Detection times and screening limits (SL) are methods used to ensure that the performance of horses in equestrian sports is not altered by drugs. Drug concentration-response relationship and knowledge of concentration-time profiles in both plasma and urine are required. In this study, dexamethasone plasma and urine concentration-time profiles were investigated. Endogenous hydrocortisone plasma concentrations and their relationship to dexamethasone plasma concentrations were also explored. A single dose of dexamethasone-21-isonicotinate suspension (0.03mg/kg) was administered intramuscularly to six horses. Plasma was analysed for dexamethasone and hydrocortisone and urine for dexamethasone, using UPLC-MS/MS. Dexamethasone was quantifiable in plasma for 8.3 +/- 2.9days (LLOQ: 0.025g/L) and in urine for 9.8 +/- 3.1days (LLOQ: 0.15g/L). Maximum observed dexamethasone concentration in plasma was 0.61 +/- 0.12g/L and in urine 4.2 +/- 0.9g/L. Terminal plasma half-life was 38.7 +/- 19h. Hydrocortisone was significantly suppressed for 140h. The plasma half-life of hydrocortisone was 2.7 +/- 1.3h. Dexamethasone potency, efficacy and sigmoidicity factor for hydrocortisone suppression were 0.06 +/- 0.04g/L, 0.95 +/- 0.04 and 6.2 +/- 4.6, respectively. Hydrocortisone suppression relates to the plasma concentration of dexamethasone. Thus, determination of irrelevant plasma concentrations and SL is possible. Future research will determine whether hydrocortisone suppression can be used as a biomarker of the clinical effect of dexamethasone.
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| 6. |
- Gabrielsson, Johan, et al.
(författare)
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Maxsim2-Real-time interactive simulations for computer-assisted teaching of pharmacokinetics and pharmacodynamics.
- 2014
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Ingår i: Computer methods and programs in biomedicine. - : Elsevier BV. - 1872-7565 .- 0169-2607. ; 113, s. 815-829
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Tidskriftsartikel (refereegranskat)abstract
- We developed a computer program for use in undergraduate and graduate courses in pharmacology, pharmacokinetics and pharmacodynamics. This program can also be used in environmental and toxicological studies and preclinical simulation, to facilitate communication between modeling pharmacokineticists and project leaders or other decision-makers in the pharmaceutical industry. The program simulates the drug delivery and transport by means of (I) a six-compartment physiological pharmacokinetic flow model, (II) a system of traditional compartment models, or (III) a target-mediated drug disposition system. The program also can be used to simulate instantaneous equilibria between concentration and pharmacodynamic response, or as temporal delays between concentration and response. The latter is done by means of turnover models (indirect response models). Drug absorption, distribution, and elimination are represented by differential equations, which are described by organ and tissue volumes or other volumes of distribution, blood flows, clearance terms, and tissue-to-blood partition coefficients. The user can control and adjust these parameters by means of a slider in real time. By interactively changing the parameter values and simultaneously displaying the resulting concentration-time and/or response-time profiles, users can understand the major mechanisms that govern the disposition or the pharmacological response of the drug in the organism in real time. Schedule dependence is typically seen in clinical practice with a non-linear concentration-response relationship, and is difficult to communicate except via simulations. Here, we sought to illustrate the potential advantages of this approach in teaching pharmacology, pharmacokinetics, and pharmacodynamics to undergraduate pharmacy-, veterinary-, and medical students or to project teams in drug discovery/development.
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| 7. |
- Gu, Yunjin, et al.
(författare)
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Toward a New Force Sensor for Twisted String Actuator : A Study about the Force on Separator
- 2017
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Ingår i: 2017 IEEE/RSJ INTERNATIONAL CONFERENCE ON INTELLIGENT ROBOTS AND SYSTEMS (IROS). - : IEEE. - 9781538626825 ; , s. 1207-1212
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Konferensbidrag (refereegranskat)abstract
- The twisted string actuator (TSA) shows promise as a good substitution for biological muscle in robotics. In this paper, a new force sensing mechanism is suggested utilizing the separator which exists in some kind of TSAs. We have identified a relation between the force acting on the separator and the load on the actuator and propose a mathematical model based on this original phenomenon. We also propose an estimation method of the load acting on the TSA using the mathematical model. This relationship has been verified in experiment. A contribution of this research is that the actuation load can be estimated by use of internal structure in TSA which in some circumstances can result in a simpler system compared to direct measurement of load in line.
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| 8. |
- Hopfgarten, Johan, et al.
(författare)
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Gene expression analysis of human islets in a subject at onset of type 1 diabetes
- 2014
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Ingår i: Acta Diabetologica. - : Springer Science and Business Media LLC. - 0940-5429 .- 1432-5233. ; 51:2, s. 199-204
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Tidskriftsartikel (refereegranskat)abstract
- Swollen islet cells have been repeatedly described at onset of type 1 diabetes, but the underlying mechanism of this observation, termed hydropic degeneration, awaits characterization. In this study, laser capture microdissection was applied to extract the islets from an organ donor that died at onset of type 1 diabetes and from an organ donor without pancreatic disease. Morphologic analysis revealed extensive hydropic degeneration in 73 % of the islets from the donor with type 1 diabetes. Expression levels of genes involved in apoptosis, ER stress, beta cell function, and inflammation were analyzed in isolated and laser-captured islets by qPCR. The chemokine MCP-1 was expressed in islets from the donor with type 1 diabetes while undetectable in the control donor. No other signs of inflammation were detected. There were no signs of apoptosis on the gene expression level, which was also confirmed by negative immunostaining for cleaved caspase-8. There was an increased expression of the transcription factor ATF4, involved in transcription of ER stress genes, in the diabetic islets, but no further signs of ER stress were identified. In summary, on the transcription level, islets at onset of type 1 diabetes in which many beta cells display hydropic degeneration show no obvious signs of apoptosis, ER stress, or inflammation, supporting the notion that these cells are responding normally to high glucose and eventually succumbing to beta cell exhaustion. Also, this study validates the feasibility of performing qPCR analysis of RNA extracted from islets from subjects with recent onset of T1D and healthy controls by laser capture microdissection.
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| 9. |
- Ingvast, Johan, 1968-
(författare)
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Quadruped robot control and variable leg transmissions
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The research presented in this thesis regards walking of quadruped robots, and particularly the walking of the Warp1 robot. The motivation for the robot is to provide a platform for autonomous walking in rough terrain. The thesis contains six papers ranging from development tools to actuation of robot legs. The first paper describes the methods and tools made for control development. These tools feature: programming of the robot without low level coding (C-code); that the controller has to be built only once for simulation and experiments; and that names of variables and constants are unchanged through the chain of software Maple -- Matlab -- Simulink -- Real~Time~Workshop -- xPC--Target. Three controllers, each making the robot walk are presented. The first controller makes the robot walk using the crawl gait. The method uses static stability as method for keeping balance and the instantaneous trunk motions are given by a concept using the so called weight ratios. A method for planning new footholds based on the positions of the existing footholds is also proposed and the controller experimentally verified. The second walking controller shows that the robot also can walk dynamically using the trot gait. The method proposed uses information from ground contact sensors on the feet as input to control balance, instead of, which is common, inertial sensors. It is experimentally verified that Warp1 can trot from level ground onto a slope and turn around while staying balanced. The main ideas of these two walking controllers are fused in the third which enables smooth transitions between crawl and trot. The idea of using the ground contact sensors from the first controller is here used to estimate the position of the center of mass. This controller uses weight ratios in the gait crawl as well as in the dynamic gait trot. Hence, the method of using weight ratios is not only useful for static stability for which it was originally intended. The controller is experimentally verified on Warp1. The Warp1 robot weighs about 60 kg, has 0.6 m long legs with three actuated joints on each. The speed and strength is sufficient only for slow walking, even though the installed power indicates that it should be enough for faster walking. The reason is that a walking robot often needs to be strong but slow when the feet are on the ground and the opposite when in the air. This can not be achieved with the motors and transmissions currently used. A transmission called the passively variable transmission (PVT) is proposed which enhance motor capabilities of robot joints. It is elastic, nonlinear and conservative. Some general properties for elastic transmissions are derived such that they can be compared with conventional transmissions. The PVT gives strong actuation at large loads and fast actuation at small loads. The proposed transmission is compared to a conventional transmission for a specific task, and the result is that a smaller motor can be used.
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| 10. |
- Ingvast, Johan, et al.
(författare)
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The PVT, an elastic conservative transmission
- 2006
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Ingår i: The international journal of robotics research. - : SAGE Publications. - 0278-3649 .- 1741-3176. ; 25:10, s. 1013-1032
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Tidskriftsartikel (refereegranskat)abstract
- This paper presents an innovative transmission called the passively variable transmission (PVT) that has a high torque ratio for large loads and a low velocity ratio for small loads. The change in these ratios depends passively on the load, in contrast to the continuous variable transmission (CVT), where the transmission ratio is controlled explicitly. Another difference from the CVT is that the PVT is elastic and the term transmission ratio is therefore not applicable. A theory section formulates alternative ways of describing the torque and velocity relations for elastic conservative transmisions as well as other important properties. This theory is used to analyze and illustrate the characteristics of a PVT. The theory is also used to compare the PVT with another novel elastic conservative transmission, called load sensitive CVT. The nonlinearities and elasticity of the PVT make it difficult to control using linear control theory. Feedback linearization was therefore used to design a torque controller, and experimental results show low impedance at small loads. Further, the controller tracks a reference torque well as long as the reference rate does not cause motor saturation. The abilities of the PVT are also illustrated by comparing it with an actuator having a traditional transmission. The load case is recorded joint torques and angles from the carpus joint of a walking horse. Simulation show that the required peak power is reduced by more than 20% and the product of the maximum torque and the maximum angular velocity is reduced by approximately 30%
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