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- Wang, Li-San, et al.
(author)
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Rarity of the Alzheimer Disease-Protective APP A673T Variant in the United States.
- 2015
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In: JAMA neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 72:2
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Journal article (peer-reviewed)abstract
- Recently, a rare variant in the amyloid precursor protein gene (APP) was described in a population from Iceland. This variant, in which alanine is replaced by threonine at position 673 (A673T), appears to protect against late-onset Alzheimer disease (AD). We evaluated the frequency of this variant in AD cases and cognitively normal controls to determine whether this variant will significantly contribute to risk assessment in individuals in the United States.
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- Alskär, Linda C., et al.
(author)
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Effect of lipids on absorption of carvedilol in dogs : Is coadministration of lipids as efficient as a lipid-based formulation?
- 2019
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In: Journal of Controlled Release. - : Elsevier BV. - 0168-3659 .- 1873-4995. ; 304, s. 90-100
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Journal article (peer-reviewed)abstract
- Lipid-based formulations (LBFs) is a formulation strategy for enabling oral delivery of poorly water-soluble drugs. However, current use of this strategy is limited to a few percent of the marketed products. Reasons for that are linked to the complexity of LBFs, chemical instability of pre-dissolved drug and a limited understanding of the influence of LBF intestinal digestion on drug absorption. The aim of this study was to explore intestinal drug solubilization from a long-chain LBF, and evaluate whether coadministration of LBF is as efficient as a lipidbased drug formulation containing the pre-dissolved model drug carvedilol. Thus, solubility studies of this weak base were performed in simulated intestinal fluid (SIF) and aspirated dog intestinal fluid (DIF). DIF was collected from duodenal stomas after dosing of water and two levels (1 g and 2 g) of LBF. Similarly, the in vitro SIF solubility studies were conducted prior to, and after addition of, undigested or digested LBF. The DIF fluid was further characterized for lipid digestion products (free fatty acids) and bile salts. Subsequently, carvedilol was orally administered to dogs in a lipid-based drug formulation and coadministered with LBF, and drug plasma exposure was assessed. In addition to these studies, in vitro drug absorption from the different formulation approaches were evaluated in a lipolysis-permeation device, and the obtained data was used to evaluate the in vitro in vivo correlation. The results showed elevated concentrations of free fatty acids and bile salts in the DIF when 2 g of LBF was administered, compared to only water. As expected, the SIF and DIF solubility data revealed that carvedilol solubilization increased by the presence of lipids and lipid digestion products. Moreover, coadministration of LBF and drug demonstrated equal plasma exposure to the lipid-based drug formulation. Furthermore, evaluation of in vitro absorption resulted in the same rank order for the LBFs as in the in vivo dog study. In conclusion, this study demonstrated increased intestinal solubilization from a small amount of LBF, caused by lipid digestion products and bile secretion. The outcomes also support the use of coadministration of LBF as a potential dosing regimen in cases where it is beneficial to have the drug in the solid form, e.g. due to chemical instability in the lipid vehicle. LBFs.
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- Brijs, J., et al.
(author)
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In vivo aerobic metabolism of the rainbow trout gut and the effects of an acute temperature increase and stress event
- 2018
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In: Journal of Experimental Biology. - : The Company of Biologists. - 0022-0949 .- 1477-9145. ; 221:14
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Journal article (peer-reviewed)abstract
- The fish gut is responsible for numerous potentially energetically costly processes, yet little is known about its metabolism. Here, we provide the first in vivo measurements of aerobic metabolism of the gut in a teleost fish by measuring gut blood flow, as well as arterial and portal venous oxygen content. At 10 degrees C, gut oxygen uptake rate was 4.3 +/- 0.5 ml O-2 h(-1) kg(-1) (similar to 11 % of whole-animal oxygen uptake). Following acute warming to 15 degrees C, gut blood flow increased similar to 3.4-fold and gut oxygen uptake rate increased similar to 3.7-fold (16.0 +/- 3.3 ml O-2 h(-1) kg(-1)), now representing similar to 25% of whole-animal oxygen uptake. Although gut blood flow decreased following an acute stress event at 15 degrees C, gut oxygen uptake remained unchanged as a result of a similar to 2-fold increase in oxygen extraction. The high metabolic thermal sensitivity of the gut could have important implications for the overall aerobic capacity and performance of fish in a warming world and warrants further investigation.
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| 8. |
- Brijs, J., et al.
(author)
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Prospects and pitfalls of using heart rate bio-loggers to assess the welfare of rainbow trout (Oncorhynchus mykiss) in aquaculture
- 2019
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In: Aquaculture. - : Elsevier BV. - 0044-8486 .- 1873-5622. ; 509, s. 188-197
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Journal article (peer-reviewed)abstract
- - Investigating real-time stress responses during common aquaculture practices is necessary for improving the welfare of farmed fish. Recently, Star-Oddi DST milli-HRT bio-loggers capable of measuring heart rate (as an indicator for stress) in freely swimming fish have proved to be useful in this regard. However, despite the growing popularity of these devices, they have not yet been stringently evaluated and validated for use in fish. The present study is the first to do so by simultaneously recording heart rate of a commercially important salmonid species (rainbow trout, Oncorhynchus mykiss) using the abovementioned bio-loggers, as well as an established non-invasive wireless heart rate recording technique that has been demonstrated to provide more accurate recordings than those collected using traditional methods requiring a physical connection to recording equipment. The measurement error of the bio-loggers was <1 beat min −1 irrespective of the sampling period when only using measurements graded with the highest quality index (QI 0 ) and it is advised that only QI 0 measurements be used as inclusion of poorer quality measurements (QI 1–3 ) markedly reduce measurement accuracy. Furthermore, sufficiently long recovery periods should be employed prior to collecting data with these devices in salmonids, as anaesthesia and surgical implantation of bio-loggers resulted in transiently elevated resting heart rates for >72 h. Following the successful validation of these bio-loggers, the effects of common aquaculture practices such as netting, grouping and enforced activity on the cardiac performance of freely swimming rainbow trout were investigated. Prior to the subsequent exposure to the abovementioned stressors, mean heart rates of trout were ~42 beats min −1 . Following netting, trout increased heart rates by 57%, which recovered within 3 h. Grouping subsequently induced a more pronounced and prolonged stress response, as heart rates initially increased by 86% and then remained elevated throughout the 8 h recovery period. Consequently, trout were only able to further increase heart rates by 7% following enforced activity. This diminished cardiac response demonstrates a situation where the cumulative allostatic load induced by prior stressors is approaching a level where the animal struggles to perform normal physiological processes in the face of further challenges. These findings are important for the aquaculture industry as exposure to multiple stressors without sufficient recovery times has the potential to result in the collapse of cardiac scope, which combined with unfavourable environmental conditions could lead to increased mortality. © 2019 Elsevier B.V.
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| 9. |
- Brijs, J., et al.
(author)
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Remote physiological monitoring provides unique insights on the cardiovascular performance and stress responses of freely swimming rainbow trout in aquaculture
- 2019
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1
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Journal article (peer-reviewed)abstract
- Investigating the mechanisms that fish employ to maintain homeostasis in their everyday life requires measurements of physiological and behavioural responses in the field. With multivariate bio-loggers, we continuously measured gastrointestinal blood flow (GBF), heart rate, activity and body temperature in rainbow trout (Oncorhynchus mykiss) swimming freely amongst ~5000 conspecifics in a sea cage. Our findings clearly demonstrate that while both acute aquaculture-related stress and spontaneous activity resulted in transient reductions in GBF (i.e. reductions of up to 65%), recovery from stressful handling practices subsequently involved a substantial and prolonged gastrointestinal hyperemia far beyond the level observed prior to the stressor. The gastrointestinal hyperemia may be necessary to repair the damage to the gastrointestinal tract caused by acute stress. Furthermore, heart rate responses to acute stress or voluntary activity differed depending on the individual’s physiological state. Stressed fish (i.e. mean heart rates >70 beats min−1) exhibited a bradycardic response to acute stress or activity, whereas fish with mean heart rates <60 beats min−1 instead demonstrated strong tachycardic responses. Remote monitoring of physiological and behavioural variables using bio-loggers can provide unique insights into ‘real-life’ responses of animals, which can largely differ from the responses observed in confined laboratory settings. © 2019, The Author(s).
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| 10. |
- Brijs, Jeroen, et al.
(author)
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The final countdown: Continuous physiological welfare evaluation of farmed fish during common aquaculture practices before and during harvest
- 2018
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In: Aquaculture. - : Elsevier BV. - 0044-8486 .- 1873-5622. ; 495, s. 903-911
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Journal article (peer-reviewed)abstract
- Welfare of farmed fish has become of increasing concern for consumers, producers, interest groups and authorities. To improve fish welfare, it is necessary to find indicators that can identify stressful situations early enough so that an intervention can take place before detrimental effects occur. By using heart rate bio-loggers in freely swimming rainbow trout (Oncorhynchus mykiss), combined with plasma cortisol levels and a range of haematological and blood chemistry parameters, we assessed the severity of stress responses induced by a range of common aquaculture practices before and during harvest. Following surgery, transportation and reintroduction with conspecifics in the sea cage, it took similar to 4 days for heart rate to stabilize and for a clear circadian rhythm in heart rate to emerge (i.e. average circadian fluctuation in heart rate of similar to 25 to 27 beats min(-1)). The presence or absence of this circadian rhythm in heart rate could inform researchers in the aquaculture industry whether or not specific farming routines induce unnecessary and prolonged stress. The elevations in heart rate caused by common farming practises such as crowding and transportation (e.g. heart rate increased by similar to 8 and 9 beats min-1 above what would normally be expected for that time of day, respectively) corresponded well with increases in plasma cortisol levels. Stressful farming practises or events (indicated by elevated plasma cortisol levels) such as air exposure during brailing and aquatic hypoxia triggered a hypoxic bradycardia until fish were released back into oxygenated water whereupon heart rate significantly increased to repay the accumulated oxygen debt. Repeated stress induced by multiple farming practises (i.e. combined stressors of crowding, brailing and transportation) clearly had a cumulative and long-lasting effect as heart rate peaked at similar to 25 beats min(-1) above what would normally be expected for that time of day. Heart rate also remained significantly elevated by similar to 9 beats min(-1) the following morning, suggesting that if rainbow trout need to be subjected to multiple stressors during consequtive days, it is recommended that sufficient time for recovery is provided between stressors. This study demonstrates that heart rate monitoring can be useful to assess stress levels of freely swimming fish in sea cages. Moreover, the use of implantable bio-loggers opens up a broad range of possible applications that will allow researchers to investigate the effects of environmental and/or anthropogenic stressors on the welfare of fish under conditions more realistic to the aquaculture industry.
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