| 1. |
- Glasbey, JC, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 2. |
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| 3. |
- Bravo, L, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 4. |
- Tabiri, S, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 7. |
- Björkman, Sven, et al.
(författare)
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Comparative pharmacokinetics of plasma- and albumin-free recombinant factor VIII in children and adults : the influence of blood sampling schedule on observed age-related differences and implications for dose tailoring
- 2010
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Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 8:4, s. 730-736
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Dose tailoring of coagulation factors requires reliably estimated and reproducible pharmacokinetics (PK) in the individual patient. OBJECTIVES: To investigate the contribution of both biological and methodological factors to the observed variability of factor VIII (FVIII) PK, with the focus on differences between children and adults, and to examine the implications for dosing. PATIENTS: Data from 52 1-6-year-old and 100 10-65-year-old patients with hemophilia A (FVIII < or = 2 IU dL(-1)) in three clinical studies were included. RESULTS: In vivo recovery was lower, weight-adjusted clearance was higher and FVIII half-life was on average shorter in children than in adults. However, a reduced blood sampling schedule for children was estimated to account for up to one half of the total observed differences. Intrapatient variance in PK was smaller than interpatient variance in 10-65-year-olds. Age and ratio of actual to ideal weight only showed weak relationships with PK parameters. Variance in PK caused large variance in the calculated dose required to maintain a target FVIII trough level during prophylactic treatment. CONCLUSION: Differences in blood sampling schedules should be taken into account when results from different PK studies are compared. However, even with this consideration, PK cannot be predicted from observable patient characteristics but must be determined for the individual. Because the influence of reducing the blood sampling was minor in comparison to the true variance between patients, a reduced blood sampling protocol can be used. Low intrapatient variability supports the use of PK measurements for dose tailoring of FVIII.
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| 10. |
- Lietzau, G, et al.
(författare)
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A High-Fat Diet Increases Activation of the Glucagon-Like Peptide-1-Producing Neurons in the Nucleus Tractus Solitarii: an Effect that is Partially Reversed by Drugs Normalizing Glycemia
- 2022
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Ingår i: Cellular and molecular neurobiology. - : Springer Science and Business Media LLC. - 1573-6830 .- 0272-4340. ; 42:6, s. 1995-2002
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Tidskriftsartikel (refereegranskat)abstract
- Glucagon-like peptide-1 (GLP-1) is a peripheral incretin and centrally active peptide produced in the intestine and nucleus tractus solitarii (NTS), respectively. GLP-1 not only regulates metabolism but also improves cognition and is neuroprotective. While intestinal GLP-1-producing cells have been well characterized, less is known about GLP-1-producing neurons in NTS. We hypothesized that obesity-induced type 2 diabetes (T2D) impairs the function of NTS GLP-1-producing neurons and glycemia normalization counteracts this effect. We used immunohistochemistry/quantitative microscopy to investigate the number, potential atrophy, and activation (cFos-expression based) of NTS GLP-1-producing neurons, in non-diabetic versus obese/T2D mice (after 12 months of high-fat diet). NTS neuroinflammation was also assessed. The same parameters were quantified in obese/T2D mice treated from month 9 to 12 with two unrelated anti-hyperglycemic drugs: the dipeptidyl peptidase-4 inhibitor linagliptin and the sulfonylurea glimepiride. We show no effect of T2D on the number and volume but increased activation of NTS GLP-1-producing neurons. This effect was partially normalized by both anti-diabetic treatments, concurrent with decreased neuroinflammation. Increased activation of NTS GLP-1-producing neurons could represent an aberrant metabolic demand in T2D/obesity, attenuated by glycemia normalization. Whether this effect represents a pathophysiological process preceding GLP-1 signaling impairment in the CNS, remains to be investigated.
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