| 1. |
- Niemi, MEK, et al.
(author)
-
- 2021
-
swepub:Mat__t
|
|
| 2. |
- Kanai, M, et al.
(author)
-
- 2023
-
swepub:Mat__t
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
- Hayes, Anthony J., et al.
(author)
-
Spinal Deformity in Aged Zebrafish Is Accompanied by Degenerative Changes to Their Vertebrae that Resemble Osteoarthritis
- 2013
-
In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:9, s. e75787-
-
Journal article (peer-reviewed)abstract
- Age-related degenerative changes within the vertebral column are a significant cause of morbidity with considerable socio-economic impact worldwide. An improved understanding of these changes through the development of experimental models may lead to improvements in existing clinical treatment options. The zebrafish is a well-established model for the study of skeletogenesis with significant potential in gerontological research. With advancing age, zebrafish frequently develop gross deformities of their vertebral column, previously ascribed to reduced trunk muscle tone. In this study, we assess degenerative changes specifically within the bone and cartilage of the vertebral column of zebrafish at 1, 2 and 3-years of age. We show increased frequency and severity of spinal deformities/curvatures with age. Underlying the most severe phenotypes are partial or complete vertebral dislocations and focal thickening of the vertebral bone at the joint margins. MicroCT examination demonstrates small defects, fractures and morphological evidence suggestive of bone erosion and remodeling (i.e. osteophytes) within the vertebrae during aging, but no significant change in bone density. Light and electron microscopic examination reveal striking agerelated changes in cell morphology, suggestive of chondroptosis, and tissue remodelling of the vertebral cartilage, particularly within the pericellular micro-environment. Glycosaminoglycan analysis of the vertebral column by HPLC demonstrates a consistent, age-related increase in the yield of total chondroitin sulfate disaccharide, but no change in sulfation pattern, supported by immunohistochemical analysis. Immunohistochemistry strongly identifies all three chondroitin/dermatan sulphate isoforms (C-0-S, C-4-S/DS and C-6-S) within the vertebral cartilage, particularly within the pericellular micro-environment. In contrast, keratan sulfate immunolocalises specifically with the notochordal tissue of the intervertebral disc, and its labelling diminishes with age. In summary, these observations raise the prospect that zebrafish, in addition to modelling skeletal development, may have utility in modelling age-related degenerative changes that affect the skeleton during senescence.
|
|
| 6. |
|
|
| 7. |
- Nandadasa, Sumeda, et al.
(author)
-
Vascular dimorphism ensured by regulated proteoglycan dynamics favors rapid umbilical artery closure at birth
- 2020
-
In: eLife. - 2050-084X. ; 9
-
Journal article (peer-reviewed)abstract
- The umbilical artery lumen closes rapidly at birth, preventing neonatal blood loss, whereas the umbilical vein remains patent longer. Here, analysis of umbilical cords from humans and other mammals identified differential arterial-venous proteoglycan dynamics as a determinant of these contrasting vascular responses. The umbilical artery, but not the vein, has an inner layer enriched in the hydrated proteoglycan aggrecan, external to which lie contraction-primed smooth muscle cells (SMC). At birth, SMC contraction drives inner layer buckling and centripetal displacement to occlude the arterial lumen, a mechanism revealed by biomechanical observations and confirmed by computational analyses. This vascular dimorphism arises from spatially regulated proteoglycan expression and breakdown. Mice lacking aggrecan or the metalloprotease ADAMTS1, which degrades proteoglycans, demonstrate their opposing roles in umbilical vascular dimorphism, including effects on SMC differentiation. Umbilical vessel dimorphism is conserved in mammals, suggesting that differential proteoglycan dynamics and inner layer buckling were positively selected during evolution.
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
- Yee, B. J., et al.
(author)
-
The effect of sibutramine-assisted weight loss in men with obstructive sleep apnoea
- 2007
-
In: Int J Obes (Lond). - : Springer Science and Business Media LLC. - 0307-0565. ; 31:1, s. 161-168
-
Journal article (peer-reviewed)abstract
- Objective:Obstructive sleep apnoea (OSA) occurs frequently in obese patients and may be reversible with weight loss. Obstructive sleep apnoea and obesity are both independent risk factors for hypertension and increased sympathetic activity. Sibutramine has been increasingly used in the management of obesity, but is relatively contraindicated in patients with hypertension. No studies have investigated the effect of sibutramine on OSA, blood pressure and heart rate. We aimed to assess the changes in OSA and cardiovascular parameters in obese men with OSA enrolled in a sibutramine-assisted weight loss programme (SIB-WL).Design:Open uncontrolled cohort study of obese male subjects with OSA in an SIB-WL.Subjects:Eighty-seven obese (body mass index =34.2+/-2.8 kg/m(2)) middle-aged (46.3+/-9.3 years) male subjects with symptomatic OSA (Epworth score 13.4+/-3.6; respiratory disturbance index (RDI) 46.0+/-23.1 events/h) completed the study.Results:At 6 months, there was significant weight loss (8.3+/-4.7 kg, P<0.0001), as well as a reduction in waist and neck circumference and sagittal height (all P<0.0001). These changes were accompanied by a reduction in OSA severity (RDI fell by 16.3+/-19.4 events/h and Epworth score by 4.5+/-4.6), both P<0.0001). There was no significant change to systolic (P=0.07) or diastolic blood pressure (P=0.87); however, there was a mild rise in resting heart rate (P<0.0001).Conclusion:Moderate ( approximately 10%) weight loss with SIB-WL results in improvement in OSA severity without increase in blood pressure in closely monitored OSA subjects.International Journal of Obesity (2007) 31, 161-168. doi:10.1038/sj.ijo.0803363; published online 2 May 2006.
|
|
