| 1. |
- Carlström, Mattias, et al.
(författare)
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Hydronephrosis causes salt-sensitive hypertension and impaired renal concentrating ability in mice
- 2007
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Ingår i: Acta Physiologica. - : Wiley. - 1748-1708 .- 1748-1716. ; 189:3, s. 293-301
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Hypertension is a common disease in the industrialized world and approximately 5% of all cases are secondary to kidney malfunction. We have recently shown that hydronephrosis due to partial unilateral ureteral obstruction (PUUO) causes salt-sensitive hypertension in rats. The mechanisms are still unclear, but appear to be intrarenal and primarily located to the diseased kidney. In the present study, we have developed a model for PUUO to study if hydronephrotic mice develop salt-sensitive hypertension. Methods: PUUO was created in 3-week-old mice (C57bl/6J). Blood pressure and heart rate were measured telemetrically in adult animals on normal and high salt diets. Metabolism cages were used to study the renal excretion of electrolytes and water. Plasma samples for renin analysis were collected and renal histological changes were evaluated. Results: All hydronephrotic animals developed salt-sensitive hypertension that correlated to the degree of hydronephrosis. In hydronephrotic animals, blood pressure increased from 114 ± 1 mmHg on normal salt diet to 120 ± 2 mmHg on high salt diet, compared with 103 ± 1 to 104 ± 1 in controls. Hydronephrotic animals showed increased diuresis and reduced ability to regulate electrolyte concentration. No differences in plasma renin concentration were found between the groups. The parenchymal weight and glomerular area of contralateral kidneys were significantly increased in the hydronephrotic animals. Histopathology of the hydronephrotic kidneys displayed areas with fibrosis, inflammation and glomerular changes. Conclusion: This study provides a model for PUUO in mice and demonstrates the presence of salt-sensitive hypertension and an impaired renal concentrating ability in mice which has not been described before.
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| 2. |
- Carlström, Mattias, et al.
(författare)
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Role of nitric oxide deficiency in the development of hypertension in hydronephrotic animals
- 2008
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Ingår i: American Journal of Physiology - Renal Physiology. - : American Physiological Society. - 0363-6127 .- 1522-1466 .- 1931-857X. ; 294:2, s. 362-370
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Tidskriftsartikel (refereegranskat)abstract
- Hydronephrotic animals develop renal injury and hypertension, which is associated with an abnormal tubuloglomerular feedback (TGF). The TGF sensitivity is coupled to nitric oxide (NO) in the macula densa. The involvement of reduced NO availability in the development of hypertension in hydronephrosis was investigated. Hydronephrosis was induced by ureteral obstruction in young rats. Blood pressure and renal excretion were measured in adulthood, under different sodium conditions, and before and after chronic administration of either N-G- nitro-L-arginine methyl ester (L-NAME) or L-arginine. Blood samples for ADMA, SDMA, and L-arginine analysis were taken and the renal tissue was used for histology and determination of NO synthase (NOS) proteins. TGF characteristics were determined by stop-flow pressure technique before and after administration of 7-nitroindazole (7-NI) or L-arginine. Hydronephrotic animals developed salt-sensitive hypertension, which was associated with pressure natriuresis and diuresis. The blood pressure response to L-NAME was attenuated and L-arginine supplementation decreased blood pressure in hydronephrotic animals, but not in the controls. Under control conditions, reactivity and sensitivity of the TGF response were greater in the hydronephrotic group. 7-NI administration increased TGF reactivity and sensitivity in control animals, whereas, in hydronephrotic animals, neuronal NOS (nNOS) inhibition had no effect. L-Arginine attenuated TGF response more in hydronephrotic kidneys than in controls. The hydronephrotic animals displayed various degrees of histopathological changes. ADMA and SDMA levels were higher and the renal expressions of nNOS and endothelial NOS proteins were lower in animals with hydronephrosis. Reduced NO availability in the diseased kidney in hydronephrosis, and subsequent resetting of the TGF mechanism, plays an important role in the development of hypertension.
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| 3. |
- Fällström, Karl-Evert, et al.
(författare)
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Transient bending waves in anisotropic plates studied by hologram interferometry
- 1989
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Ingår i: Experimental mechanics. - 0014-4851 .- 1741-2765. ; 29:4, s. 409-413
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Tidskriftsartikel (refereegranskat)abstract
- Propagating bending waves are studied in plates made of glass-fiber reinforced polyester. The waves are generated by the impact of a ballistic pendulum. Hologram interferometry, with a double pulsed ruby laser as light source, is used to record the out of plane motion of the waves. The interferograms have an elliptic-like symmetry for an orthotropic plate, while the wave pattern for a symmetric angle-ply reinforced plate has a symmetry about the axes of reinforcements. Experimental data are compared on one hand to analytical results obtained by assuming that the orthotropic plate can be described as if isotropic along the main axes, and on the other hand to numerical results from calculations using the finite-element method. The effective Young's modulus raised to power 1/4 is shown to be an important parameter for the description of the dispersive wave pattern. A defect in the plate alters the wave pattern in the interferograms significantly. This may have technical use.
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| 4. |
- Molin, Nils-Erik, et al.
(författare)
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Transient wave response of the violin body
- 1990
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Ingår i: Journal of the Acoustical Society of America. - : Acoustical Society of America (ASA). - 0001-4966 .- 1520-8524. ; 88:5, s. 2479-2481
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Tidskriftsartikel (refereegranskat)abstract
- In this investigation, the dispersive, transient wave propagation field of a complete violin excited by a mechanically induced impulse at the top of the bridge is presented. By means of double pulsed holographic interferometry with a ruby laser as light source the propagating wave field is recorded. From presented interferograms, it is seen that initially the top plate acts mainly as a nonsymmetric dipole with centers at the two bridge feet. The back plate is strongly coupled to the motion of the top plate by the sound post and acts more like a monopole. Thus the position of the sound post is crucial to the performance of the instrument. The free edges at the f-holes are very early reached by the dispersive bending waves of high amplitude probably giving a significant contribution to the sound of the violin family instruments
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| 5. |
- Molin, Nils-Erik, et al.
(författare)
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Transient wave response of the violin body revisited
- 1991
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Ingår i: Journal of the Acoustical Society of America. - : Acoustical Society of America (ASA). - 0001-4966 .- 1520-8524. ; 90:4, s. 2192-2195
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Tidskriftsartikel (refereegranskat)abstract
- In this investigation, the dispersive, transient wave propagation field of the top plate of a complete violin excited by a mechanically induced pulse at the top of the bridge is presented. A similar investigation has previously been made for excitation parallel with the top plate and is now completed with excitation perpendicular to the plate. From presented interferograms, it is seen that the top plate initially deforms in a nonsymmetric two-pole with centers at the two bridge feet. Shortly thereafter the two poles (valleys) are joined into one, but after 0.30 ms the displacement is still nonsymmetric with maximum motion at the bridge foot closest to the excitation point. From the measurements it can be concluded that for excitation parallel with the top plate, the plate between the f-holes acts mainly as a dipole, but with excitation perpendicular the same part acts mainly as a monopole. Thus the excitation of the top plate when playing the violin depends on the angle of the bow in relation to the top plate and should influence the tone character
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| 6. |
- Peleli, Maria, et al.
(författare)
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Renal denervation attenuates NADPH oxidase-mediated oxidative stress and hypertension in rats with hydronephrosis
- 2016
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Ingår i: American Journal of Physiology - Renal Physiology. - : American Physiological Society. - 0363-6127 .- 1522-1466 .- 1931-857X. ; 310:1, s. F43-F56
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Tidskriftsartikel (refereegranskat)abstract
- Hydronephrosis is associated with development of salt-sensitive hypertension. Studies suggest that increased sympathetic nerve activity (SNA) and oxidative stress play important roles in renovascular hypertension. This study aimed to investigate the link between renal SNA and NADPH oxidase (NOX) regulation in the development of hypertension in rats with hydronephrosis. Hydronephrosis was induced by partial unilateral ureteral obstruction (PUUO) in young rats. Sham surgery or renal denervation was performed at the same time. Blood pressure was measured during normal, high and low salt diets. Renal excretion pattern, NOX activity and expression, as well as components of RAAS were characterized. On normal salt diet, PUUO rats had elevated blood pressure compared with controls (115±3 vs 87±1 mmHg), and displayed increased urine production and lower urine osmolality. Blood pressure change in response to salt loading (salt-sensitivity) was more pronounced in the PUUO group compared with controls (15±2 vs 5±1mmHg). Renal denervation in PUUO rats attenuated hypertension (97±3mmHg) and salt-sensitivity (5±1mmHg), and normalized renal excretion pattern, whereas the degree of renal fibrosis and inflammation was not changed. NOX activity and expression, as well as renin and AT1A receptor expression, were increased in renal cortex from PUUO rats, and normalized by denervation. Plasma sodium and potassium levels were elevated in PUUO rats and normalized after renal denervation. Denervation in PUUO rats was also associated with reduced NOX expression, superoxide production and fibrosis in the heart. This study emphasizes a link between renal nerves, NOX function, and development of hypertension.
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| 7. |
- Al-Mashhadi, Ammar Nadhom Farman, et al.
(författare)
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Changes in arterial pressure and markers of nitric oxide homeostasis and oxidative stress following surgical correction of hydronephrosis in children
- 2018
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Ingår i: Pediatric nephrology (Berlin, West). - : Springer. - 0931-041X .- 1432-198X. ; 33:4, s. 639-649
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Tidskriftsartikel (refereegranskat)abstract
- Objective Recent clinical studies have suggested an increased risk of elevated arterial pressure in patients with hydronephrosis. Animals with experimentally induced hydronephrosis develop hypertension, which is correlated to the degree of obstruction and increased oxidative stress. In this prospective study we investigated changes in arterial pressure, oxidative stress, and nitric oxide (NO) homeostasis following correction of hydronephrosis.Methods Ambulatory arterial pressure (24 h) was monitored in pediatric patients with hydronephrosis (n = 15) before and after surgical correction, and the measurements were compared with arterial pressure measurements in two control groups, i.e. healthy controls (n = 8) and operated controls (n = 8). Markers of oxidative stress and NO homeostasis were analyzed in matched urine and plasma samples.Results The preoperative mean arterial pressure was significantly higher in hydronephrotic patients [83 mmHg; 95% confidence interval (CI) 80–88 mmHg] than in healthy controls (74 mmHg; 95% CI 68–80 mmHg; p < 0.05), and surgical correction of ureteral obstruction reduced arterial pressure (76 mmHg; 95% CI 74–79 mmHg; p < 0.05). Markers of oxidative stress (i.e., 11- dehydroTXB2, PGF2α, 8-iso-PGF2α, 8,12-iso-iPF2α-VI) were significantly increased (p < 0.05) in patients with hydronephrosis compared with both control groups, and these were reduced following surgery (p < 0.05). Interestingly, there was a trend for increased NO synthase activity and signaling in hydronephrosis, which may indicate compensatory mechanism(s).Conclusion This study demonstrates increased arterial pressure and oxidative stress in children with hydronephrosis compared with healthy controls, which can be restored to normal levels by surgical correction of the obstruction. Once reference data on ambulatory blood pressure in this young age group become available, we hope cut-off values can be defined for deciding whether or not to correct hydronephrosis surgically.Keywords Blood pressure . Hydronephrosis . Hypertension . Nitric oxide . Oxidative stress . Ureteral obstruction
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| 8. |
- Allentoft, Morten E., et al.
(författare)
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100 ancient genomes show repeated population turnovers in Neolithic Denmark
- 2024
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Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 625, s. 329-337
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Tidskriftsartikel (refereegranskat)abstract
- Major migration events in Holocene Eurasia have been characterized genetically at broad regional scales1–4. However, insights into the population dynamics in the contact zones are hampered by a lack of ancient genomic data sampled at high spatiotemporal resolution5–7. Here, to address this, we analysed shotgun-sequenced genomes from 100 skeletons spanning 7,300 years of the Mesolithic period, Neolithic period and Early Bronze Age in Denmark and integrated these with proxies for diet (13C and 15N content), mobility (87Sr/86Sr ratio) and vegetation cover (pollen). We observe that Danish Mesolithic individuals of the Maglemose, Kongemose and Ertebølle cultures form a distinct genetic cluster related to other Western European hunter-gatherers. Despite shifts in material culture they displayed genetic homogeneity from around 10,500 to 5,900 calibrated years before present, when Neolithic farmers with Anatolian-derived ancestry arrived. Although the Neolithic transition was delayed by more than a millennium relative to Central Europe, it was very abrupt and resulted in a population turnover with limited genetic contribution from local hunter-gatherers. The succeeding Neolithic population, associated with the Funnel Beaker culture, persisted for only about 1,000 years before immigrants with eastern Steppe-derived ancestry arrived. This second and equally rapid population replacement gave rise to the Single Grave culture with an ancestry profile more similar to present-day Danes. In our multiproxy dataset, these major demographic events are manifested as parallel shifts in genotype, phenotype, diet and land use.
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| 9. |
- Allentoft, Morten E., et al.
(författare)
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Population genomics of post-glacial western Eurasia
- 2024
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Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 625:7994, s. 301-311
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Tidskriftsartikel (refereegranskat)abstract
- Western Eurasia witnessed several large-scale human migrations during the Holocene1–5. Here, to investigate the cross-continental effects of these migrations, we shotgun-sequenced 317 genomes—mainly from the Mesolithic and Neolithic periods—from across northern and western Eurasia. These were imputed alongside published data to obtain diploid genotypes from more than 1,600 ancient humans. Our analyses revealed a ‘great divide’ genomic boundary extending from the Black Sea to the Baltic. Mesolithic hunter-gatherers were highly genetically differentiated east and west of this zone, and the effect of the neolithization was equally disparate. Large-scale ancestry shifts occurred in the west as farming was introduced, including near-total replacement of hunter-gatherers in many areas, whereas no substantial ancestry shifts happened east of the zone during the same period. Similarly, relatedness decreased in the west from the Neolithic transition onwards, whereas, east of the Urals, relatedness remained high until around 4,000 bp, consistent with the persistence of localized groups of hunter-gatherers. The boundary dissolved when Yamnaya-related ancestry spread across western Eurasia around 5,000 bp, resulting in a second major turnover that reached most parts of Europe within a 1,000-year span. The genetic origin and fate of the Yamnaya have remained elusive, but we show that hunter-gatherers from the Middle Don region contributed ancestry to them. Yamnaya groups later admixed with individuals associated with the Globular Amphora culture before expanding into Europe. Similar turnovers occurred in western Siberia, where we report new genomic data from a ‘Neolithic steppe’ cline spanning the Siberian forest steppe to Lake Baikal. These prehistoric migrations had profound and lasting effects on the genetic diversity of Eurasian populations.
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| 10. |
- Carlström, Mattias, 1978-
(författare)
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Development of Salt-Sensitive Hypertension in Hydronephrosis
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Hydronephrosis, due to ureteropelvic junction obstruction, is a common condition in infants with an incidence of approximately 0.5-1%. During the last decade, the surgical management of non-symptomatic hydronephrosis has become more conservative, and the long-term physiological consequences of this new policy are unclear. The overall aim of this thesis was to determine whether there is a link between hydronephrosis and the development of hypertension. Hydronephrosis was induced by partial ureteral obstruction in 3-week old rats or mice. In the adult animals, blood pressure was measured telemetrically during different sodium conditions and the renal function was evaluated. Both species developed salt-sensitive hypertension and histopathological changes (i.e. fibrosis, inflammation, glomerular and tubular changes) that correlated with the degree of hydronephrosis. An abnormal renal excretion pattern with increased diuresis and impaired urine concentrating ability was observed in hydronephrosis. The mechanisms were primarily located to the diseased kidney, as relief of the obstruction attenuated blood pressure and salt-sensitivity. Increased renin angiotensin system activity, due to ureteral obstruction, might be involved in the development but not necessary the maintenance of hypertension. Hydronephrotic animals displayed reduced nitric oxide availability, which might be due to increased oxidative stress in the diseased kidney. Renal nitric oxide deficiency and subsequent resetting of the tubuloglomerular feedback mechanism, appeared to have an important role in the development of hypertension. In conclusion, experimental hydronephrosis, induced by partial ureteral obstruction, provides a new model for studies of salt-sensitive hypertension. Furthermore, the new findings imply that the current conservative treatment strategy in hydronephrosis should be reconsidered in favour of treatment that is more active, in order to prevent the development of renal injury and hypertension in later life.
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