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| 2. |
- Asgeirsson, Daniel, et al.
(författare)
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Glomerular sieving of three neutral polysaccharides and bikunin in rat. - Effects of molecular size and conformation.
- 2007
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Ingår i: Acta Physiologica. - : Wiley. - 1748-1708 .- 1748-1716. ; 191:3, s. 237-246
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Polysaccharides and many other non-protein polymers generally have a more open, flexible and asymmetrical structure compared with globular proteins. For a given molecular weight (MW), the Stokes–Einstein radius (ae) of the following polymers increases in the order: Ficoll < dextran ≤ pullulan < polyethylene oxide (PEO). We have tested the hypothesis that such an increase in 'molecular extension' will increase the molecule's glomerular permeability. Thus, we investigated the glomerular sieving coefficients (θ) of the mentioned polymers and of the negatively charged and extended protein bikunin. Methods: In anaesthetized Wistar rats, glomerular sieving curves were generated for each FITC-labelled polymer from their respective concentration in urine and plasma, determined by size exclusion chromatography. The θ for bikunin was measured using a tissue uptake technique. Results: For a molecule of ae = 55 Å (cf. IgG), θ increased in the order: Ficoll (0.00035 ± 0.000013) < dextran (0.022 ± 0.0029) < pullulan (0.033 ± 0.0024) < PEO (0.12 ± 0.0055). For ae = 36 Å (cf. albumin) the order was: Ficoll (0.076 ± 0.0061) < dextran (0.45 ± 0.037) = pullulan (0.45 ± 0.021) < PEO (0.65 ± 0.0076). θ for bikunin (0.089 ± 0.0045) was 150 times higher than that of albumin, having an equivalent ae and net negative charge. Conclusion: From these results it is concluded that for flexible and asymmetric macromolecules, their degree of glomerular hyperpermeability is proportional to their degree of 'molecular extension'. Thus, compared with globular proteins, the polysaccharides investigated, including Ficoll, were found to be hyperpermeable across the glomerular filter in vivo.
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| 3. |
- Asgeirsson, Daniel, et al.
(författare)
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Similitude of permeabilities for Ficoll, pullulan, charge-modified albumin and native albumin across the rat peritoneal membrane.
- 2009
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Ingår i: Acta Physiologica. - : Wiley. - 1748-1708 .- 1748-1716. ; 196:4, s. 427-433
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Aim: Compared to neutral globular proteins, neutral polysaccharides, such as dextran, pullulan and Ficoll, appear hyperpermeable across the glomerular filtration barrier. This has been attributed to an increased flexibility and/or asymmetry of polysaccharides. The present study investigates whether polysaccharides are hyperpermeable also across the continuous capillaries in the rat peritoneum. Methods: In anesthetized Wistar rats, FITC-Ficoll or FITC-pullulan together with (125)I-human serum albumin (RISA) or neutralized (125)I-bovine serum albumin (nBSA) were given intravenously, after which peritoneal dialysis using conventional peritoneal dialysis fluid (Gambrosol 1.5%) was performed for 120 min. Concentrations of FITC-polysaccharides and radioactive albumin species in plasma and dialysis fluid were analyzed with high performance size exclusion chromatography and a gamma counter, respectively. Transperitoneal clearance values were calculated for polysaccharides in the molecular radius range 36-150 A, and for RISA and nBSA. Results: Ficoll and pullulan showed more or less identical permeabilities, compared to RISA and nBSA, across the peritoneal membrane. Although RISA-clearance, 5.50+/-0.28 (muL/min; +/-SEM), tended to be lower than the clearances of Ficoll(36A) (6.55+/-0.25), pullulan(36A) (6.08+/-0.22) and nBSA (6.56+/-0.23), the difference was not statistically significant. This is in contrast to the hyperpermeability exhibited by polysaccharides across the glomerular filtration barrier and also contrasts with the charge selectivity of the latter. Conclusion: The phenomenon of molecular flexibility is more important for a macromolecule's permeability through the glomerular filter than across the continuous peritoneal capillary endothelium. Furthermore, it seems that charge plays a subordinate role in the steady-state transport across the combined peritoneal capillary-interstitial barrier.
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| 4. |
- Barg, Sebastian, 1969-, et al.
(författare)
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Compensatory endocytosis in chromaffin cells
- 2008
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Ingår i: Acta Physiologica. - : Wiley. - 1748-1708 .- 1748-1716. ; 192:2, s. 195-201
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Forskningsöversikt (refereegranskat)abstract
- Exocytosis occurs via fusion of secretory granules with the cell membrane, whereupon the granule content is at least partially released and the granule membrane is temporarily added to the plasma membrane. Exocytosis is balanced by compensatory endocytosis to achieve net equilibrium of the cell surface area and to recycle and redistribute components of the exocytosis machinery. The underlying molecular mechanisms remain a matter of debate. In this review, we summarize and discuss recent progress in the understanding of compensatory endocytosis, with the focus on chromaffin cells as a useful model for studying mechanisms of regulated secretion.
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| 5. |
- Cao, Lei, et al.
(författare)
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Secondhand cigarette smoke exposure causes upregulation of cerebrovascular 5-HT(1B) receptors via the Raf/ERK/MAPK pathway in rats.
- 2013
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Ingår i: Acta Physiologica. - : Wiley. - 1748-1716 .- 1748-1708. ; 207:1, s. 183-193
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Tidskriftsartikel (refereegranskat)abstract
- AIM: Cigarette smoke exposure increases the risk of stroke. Upregulation of 5-hydroxytryptamine 1B (5-HT(1B) ) receptors is associated with the pathogenesis of cerebral ischemia. The present study examined the hypothesis that the expression of 5-HT(1B) receptors is altered in brain vessels after secondhand smoke (SHS) exposure. METHODS: Rats were exposed to SHS in vivo for 200 min daily for 8 weeks. The contractile responses of isolated cerebral arteries were studies by a sensitive myograph. The mRNA and protein expression for 5-HT(1B) receptors were examined by real-time PCR, Western blot and immunofluorescence, respectively. In addition, the phosphorylation of Raf/extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinases (MAPK) pathway was evaluated. RESULTS: The results showed that SHS exposure shifted the 5-HT(1B) receptor-mediated concentration-contraction curve toward the left with a markedly increased maximum contraction. Furthermore, there were significant elevations in mRNA level and protein expression of 5-HT(1B) receptors in SHS-exposed rats. Immunostaining revealed that the 5-HT(1B) receptors were localized to the smooth muscle cells of cerebral arteries. SHS was also found to induce the phosphorylation of Raf-1 and ERK1/2 proteins. The administration of a Raf-1 inhibitor GW5074 attenuated the 5-HT(1B) receptor upregulation. CONCLUSION: SHS exposure upregulates cerebrovascular 5-HT(1B) receptors in rats. The receptor upregulation is associated with Raf/ERK/MAPK activation. © 2012 The Authors Acta Physiologica © 2012 Scandinavian Physiological Society.
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| 6. |
- Lindqvist, Helen, 1977, et al.
(författare)
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Influence of herring (Clupea harengus) and herring fractions on metabolic status in rats fed a high energy diet.
- 2009
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Ingår i: Acta physiologica (Oxford, England). - : Wiley. - 1748-1716 .- 1748-1708. ; 196:3, s. 303-14
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Tidskriftsartikel (refereegranskat)abstract
- AIM: Few dietary studies have looked beyond fish oil to explain the beneficial metabolic effects of a fish-containing diet. Our aim was to study whether addition of herring, or sub-fractions of herring, could counteract negative metabolic effects known to be induced by a high-fat, high-sugar diet. METHODS: Rats were given six different diets: standard pellets; high energy diet with chicken mince (HiE control); high energy diet with herring mince (HiE herring); and high energy diet with chicken mince and either herring oil (HiE herring oil), herring press juice, PJ (HiE PJ) or herring low molecular weight PJ (HiE LMW-PJ). Factors associated with the metabolic syndrome were measured. RESULTS: There were no differences in energy intake or body weight between the groups, but animals fed high energy diets had a higher body fat content compared with the pellet group, although not statistically significant in all groups. Mesenteric adipocyte size was smaller in the HiE herring oil group compared with the HiE control. Glucose clamp studies showed that, compared with the pellet group, the HiE control and HiE herring diets, but not the HiE herring oil diet, induced insulin resistance. Addition of herring or herring oil to the high energy diet decreased total cholesterol levels, triacylglycerols and the atherogenic index compared with the HiE control group. CONCLUSIONS: The results suggest that addition of herring or herring oil counteracts negative effects on blood lipids induced by a high energy diet. The lipid component of herring thus seems to be responsible for these beneficial effects.
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| 7. |
- Lundborg, Göran, et al.
(författare)
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Hand function after nerve repair.
- 2007
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Ingår i: Acta Physiologica. - : Wiley. - 1748-1708 .- 1748-1716. ; 189:2, s. 207-217
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Tidskriftsartikel (refereegranskat)abstract
- Treatment of injuries to major nerve trunks in the hand and upper extremity remains a major and challenging reconstructive problem. Such injuries may cause long-lasting disabilities in terms of lost fine sensory and motor functions. Nowadays there is no surgical repair technique that can ensure recovery of tactile discrimination in the hand of an adult patient following nerve repair while very young individuals usually regain a complete recovery of functional sensibility. Post-traumatic nerve regeneration is a complex biological process where the outcome depends on multiple biological and environmental factors such as survival of nerve cells, axonal regeneration rate, extent of axonal misdirection, type of injury, type of nerve, level of the lesion, age of the patient and compliance to training. A major problem is the cortical functional reorganization of hand representation which occurs as a result of axonal misdirection. Although protective sensibility usually occurs following nerve repair, tactile discriminative functions seldom recover - a direct result of cortical remapping. Sensory re-education programmes are routinely applied to facilitate understanding of the new sensory patterns provided by the hand. New trends in hand rehabilitation focus on modulation of central nervous processes rather than peripheral factors. Principles are being evolved to maintain the cortical hand representation by using the brain capacity for visuo-tactile and audio-tactile interaction for the initial phase following nerve injury and repair (phase 1). After the start of the re-innervation of the hand (phase 2), selective de-afferentation, such as cutaneous anaesthesia of the forearm of the injured hand, allows expansion of the nerve-injured cortical hand representation, thereby enhancing the effects of sensory relearning. Recent data support the view that training protocols specifically addressing the relearning process substantially increase the possibilities for improved functional outcome after nerve repair.
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| 8. |
- Meidute, Sandra, et al.
(författare)
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Imidazoline-induced amplification of glucose- and carbachol-stimulated insulin release includes a marked suppression of islet NO generation in the mouse.
- 2009
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Ingår i: Acta Physiologica. - : Wiley. - 1748-1708 .- 1748-1716. ; 195:3, s. 375-383
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Tidskriftsartikel (refereegranskat)abstract
- Aim: The role of islet nitric oxide (NO) production in insulin releasing mechanisms is unclear. We examined whether the beneficial effects of the imidazoline derivative RX 871024 (RX) on beta-cell function might be related to perturbations of islet NO production. Methods: Experiments were performed with isolated islets or intact mice challenged with glucose or carbachol with or without RX treatment. Insulin was determined with radioimmunoassay, NO generation with high-performance liquid chromatography and expression of inducible NO-synthase (iNOS) with confocal microscopy. Results: RX treatment, in doses lacking effects on basal insulin, greatly amplified insulin release stimulated by the NO-generating secretagogues glucose and carbachol both in vitro and in vivo. RX also improved the glucose tolerance curve. Islets incubated at high glucose (20 mmol/l) displayed increased NO production derived from both neuronal constitutive NO-synthase (ncNOS) and iNOS. RX abrogated this glucose-induced NO production concomitant with amplification of insulin release. Confocal microscopy revealed abundant iNOS expression in beta-cells after incubation of islets at high but not low glucose. This was abolished after RX treatment. Similarly, islets cultured for 24 h at high glucose showed intense iNOS expression in beta-cells. This was abrogated with RX and followed by an amplified glucose-induced insulin release. Conclusion: RX effectively counteracts the negative impact of beta-cell NO generation on insulin release stimulated by glucose and carbachol suggesting imidazoline compounds by virtue of NOS-inhibitory properties being of potential therapeutic value for treatment of beta-cell dysfunction in hyperglycaemia and type 2 diabetes.
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| 9. |
- Rahman, Awahan, et al.
(författare)
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The role of Caveolin-1 in cardiovascular regulation.
- 2009
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Ingår i: Acta Physiologica. - : Wiley. - 1748-1708 .- 1748-1716. ; Sep 25, s. 231-245
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Caveolae are omega-shaped membrane invaginations present in essentially all cell types in the cardiovascular system, and numerous functions have been ascribed to these structures. Caveolae formation depends on caveolins, cholesterol, and PTRF-Cavin (polymerase I and transcript release factor-Cavin). The current review summarizes and critically discusses the cardiovascular phenotypes reported in caveolin-1-deficient mice. Major changes in the structure and function of heart, lung, and blood vessels have been documented, suggesting that caveolae play a critical role at the interface between blood and surrounding tissue. According to an emerging paradigm many of these changes are secondary to uncoupling of endothelial nitric oxide synthase. Thus, nitric oxide synthase not only synthesizes more nitric oxide in the absence of caveolin-1, but also more superoxide with potential pathogenic consequences. It is further argued that the vasodilating drive from increased nitric oxide production in caveolin-1-deficient mice is balanced by changes in the vascular media that favour increased dynamic resistance regulation. Harnessing the therapeutic opportunities buried in caveolae, while challenging, could expand the arsenal of treatment options in cancer, lung disease, and atherosclerosis.
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| 10. |
- Rådegran, Göran
(författare)
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Exercise limb blood flow response to acute and chronic hypoxia in Danish lowlanders and Aymara natives
- 2008
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Ingår i: Acta Physiologica. - : Wiley. - 1748-1708 .- 1748-1716. ; 192:4, s. 531-539
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Tidskriftsartikel (refereegranskat)abstract
- Aim: The femoral artery blood flow response to submaximal, one-legged, dynamic, knee-extensor exercise was determined in acute and chronic hypoxia to investigate the hypotheses that with adaptation to chronic hypoxia blood haemoglobin increases, allowing preservation of blood flow as in normoxia. Methods: Sixteen Danish lowlanders participated, in groups of six to eight, in the experiments at sea level normoxia (FiO(2) congruent to 0.21) and acute hypoxia (FiO(2) congruent to 0.11), and chronic hypoxia after similar to 7 and 9-10 weeks at similar to 5260 m altitude breathing ambient air (FiO(2) congruent to 0.21) or a hyperoxic gas (FiO(2) congruent to 0.55). The response was compared with that in six Aymara natives. Results: The haemoglobin and haematocrit increased (P < 0.003) in the lowlanders at altitude vs. at sea level by similar to 39 and 27% respectively; i.e. to a similar (P = ns) level as in the natives. At rest, blood flow was the same (P = ns) in the lowlanders at sea level and altitude, as in the natives at altitude. During the onset of and incremental exercise, blood flow was the same (P = ns) in the lowlanders at sea level and altitude, as in the natives at altitude. Acute hypoxia increased (P < 0.05) blood flow by similar to 55% during exercise in the lowlanders at sea level. Acute hyperoxia decreased (P < 0.05) blood flow by similar to 22-29% during exercise in the lowlanders and natives at altitude. Conclusion: In chronic hypoxia, blood haemoglobin increases, allowing normalization of the elevated exercise blood flow response in acute hypoxia, and preservation of the kinetics and steady-state exercise blood flow as in normoxia, being similar as in the natives at altitude.
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