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A Andersson

Publications and source records attributed to A Andersson.

At least 55 records · Page 3Linked to original sources
PubMed2000

Cytokine-induced functional suppression of microencapsulated rat pancreatic islets in vitro.

BACKGROUND: It is likely that inflammatory cytokines are released near microencapsulated islets in vivo. METHODS: Rates of insulin release or glucose oxidation were measured after culture of microencapsulated rat islets with interleukin (IL)-1beta and tumor necrosis factor-(TNF-alpha). Their ability to recover from IL-1beta-induced suppression was also investigated. RESULTS: Microencapsulated islets were suppressed after exposure to IL-1beta, which was potentiated by TNF-alpha. After exposure to lower IL-1beta concentrations, microencapsulated islets had similar oxidation rates as corresponding controls. At higher concentrations, microencapsulated islets were more suppressed than nonencapsulated islets. Microencapsulated and control islets were able to recover from suppression after exposure to 2.5 U/ml of IL-1beta. CONCLUSIONS: Microencapsulation using the present alginate/poly-L-lysine/alginate capsules does not protect islets against the detrimental effects of IL-1beta and TNF-alpha. Indeed, microencapsulated islets seem to be more susceptible to suppression at higher concentrations of IL-1beta. However, after exposure to a lower concentration of IL-1beta, microencapsulated islets can recover.

Animals↗
PubMed2000

Effects of ethanol on phosphoinositide hydrolysis and muscarinic acetylcholine receptor number in SH-SY5Y cells.

Previous studies suggest that the effects of ethanol on carbachol-stimulated I(1,4,5)P3 formation and on the number of mAChRs may be independent of each other. The aim of this work was to further study this hypothesis. Human neuroblastoma SH-SY5Y cells were used as a model system. Acute exposure of the cells to 100 mM ethanol induced a decrease in [3H]N-methylscopolamine ([3H]NMS) binding at 30 seconds which was of lower magnitude and of shorter duration than the previously described ethanol-induced inhibition of the peak of carbachol-stimulated I(1,4,5)P3 formation. Long-term ethanol treatment of the cells induced a time- and concentration-dependent increase in [3H]NMS binding. Three hours of 100 mM ethanol treatment were sufficient to increase the number of mAChRs at the cell surface but these receptors were not immediately functionally active, suggesting that they may be newly synthesized. Furthermore, the ethanol-induced potentiation of carbachol-stimulated I(1,4,5)P3 formation, after two days, was, for all ethanol concentrations tested, of higher magnitude than the ethanol-induced increase in mAChR number. Together, these data indicate that both acute and chronic ethanol-induced changes in carbachol-stimulated I(1,4,5)P3 formation may not only be explained by changes in mAChR density at the cell surface but may rather be the consequence of actions of ethanol down-stream of the receptor.

Binding Sites↗
PubMed2000

Hypomethylation as a cause of homocysteine-induced cell damage in human cell lines.

Despite the growing evidence that plasma homocysteine is a cardiovascular risk factor, the mechanism behind the vascular injuries is still unknown. In the present study we have investigated the possible role of hypomethylation as a cause of homocysteine-induced cell damage in two human cell lines. A significant growth retardation was observed in HeLa cell cultures in the combined presence of homocysteine and adenosine, but first at concentrations of 250 micromol/l of each. A significant decrease of intracellular glutathione concentration was noted both in the presence of homocysteine (250 micromol/l) alone and in the presence of the combination of homocysteine and adenosine (250 micromol/l). Intracellular concentration of homocysteine was increased to a similar extent both in the presence of homocysteine alone and in the presence of a combination of homocysteine and adenosine. Similar findings to those described for HeLa cell cultures were observed in endothelial cell cultures. Furthermore, in the presence of copper ions together with 100 micromol/l of adenosine and homocysteine a significantly retarded cell growth was observed in HeLa cell cultures. This finding shows that a combination of two potentially cell-damaging mechanisms (formation of oxygen radicals and hypomethylation) aggravated the retardation of cell growth compared to only one of these mechanisms being present. Thus, it is likely that several mechanisms of homocysteine-induced cell damage contribute to the increased rate of the atherogenic process observed in hyperhomocysteinemia.

Adenosine↗
PubMed2000

Chronically decreased oxygen tension in rat pancreatic islets transplanted under the kidney capsule.

BACKGROUND: A factor of potential importance in the failure of islet grafts is poor or inadequate engraftment of the islets in the implantation organ. This study measured the oxygen tension and blood perfusion in 1-, 2-, and 9-month-old islet grafts. METHODS: The partial pressure of oxygen was measured in pancreatic islets transplanted beneath the renal capsule of diabetic and nondiabetic recipient rats with a modified Clark electrode (outer tip diameter 2-6 microm). The size of the graft (250 islets) was by purpose not large enough to cure the diabetic recipients. The oxygen tension in islets within the pancreas was also recorded. Blood perfusion was measured with the laser-Doppler technique. RESULTS: Within native pancreatic islets, the partial pressure of oxygen was approximately 40 mm Hg (n=8). In islets transplanted to nondiabetic animals, the oxygen tension was approximately 6-7 mm Hg 1, 2, and 9 months posttransplantation. No differences could be seen between the different time points after transplantation. In the diabetic recipients, an even more pronounced decrease in graft tissue oxygen tension was recorded. The mean oxygen tension in the superficial renal cortex surrounding the implanted islets was similar in all groups (approximately 15 mm Hg). Intravenous administration of glucose (0.1 gxkg(-1)x min(-1)) did not affect the oxygen tension in any of the investigated tissues. The islet graft blood flow was similar in all groups, measuring approximately 50% of the blood flow in the kidney cortex. CONCLUSION: The oxygen tension in islets implanted beneath the kidney capsule is markedly lower than in native islets up to 9 months after transplantation. Moreover, persistent hyperglycemia in the recipient causes an even further decrease in graft oxygen tension, despite similar blood perfusion. To what extent this may contribute to islet graft failure remains to be determined.

Animals↗
PubMed2000

Phorbol ester induced changes in tight and adherens junctions in the choroid plexus epithelium and in the ependyma.

The molecular composition and functional properties of cell-cell junctions of choroid plexus epithelial cells and the ependyma of the lateral ventricular wall were investigated in the rat brain. Expression studies of cadherin and alpha- and beta-catenins, as well as expression of occludin and ZO-1, indicated that cell adherens and tight junctions were present in both choroid plexus epithelial cells and in ependymal cells. We then tested the hypothesis that phorbolester in vivo can induce changes in the expression level of adherens and tight junction molecules at the blood-cerebrospinal fluid (CSF) barrier as well as in the ependyma. In addition, the functional properties of the ependymal junctions were tested by injection of dextran 3000 into the striatum after phorbolester application. Twenty-four hours after phorbolester-injection into the lateral ventricle of the rat brain, the expression patterns of tight and adherens junction molecules were markedly changed in the epithelial cells of the choroid plexus. The adherens junction proteins cadherin and beta-catenin were reduced in both the ependymal cells of the lateral ventricle and choroid plexus epithelial cells. In addition, the occludin-immunoreactivity of the choroid plexus epithelial cells was strongly reduced. However, the ZO-1 immunoreactivity was not affected by the phorbol ester-treatment and the alpha-catenin immunoreactivity was not changed. Furthermore, phorbol ester injection induced a reduction of the volume of intrastriatal injected biotinylated dextran (m.w. 3000), which is consistent with a modulatory influence of protein kinase C activation on the clearance capacity of the brain.

Animals↗
PubMed2000

Redox status of plasma homocysteine and other plasma thiols in stroke patients.

Despite the growing evidence that plasma homocysteine is a cardiovascular risk factor, the mechanism behind the vascular injuries is still unknown. Studies are difficult as a result of the fact that little is known about the formation of different homocysteine species in vivo. Since extracellular glutathione and cysteine may influence the formation of different homocysteine species, we have in the present study investigated the different fractions of homocysteine and their relation to the different fractions of glutathione and cysteine in stroke patients and control subjects. We found a ratio of about 32-33% between reduced and total plasma glutathione concentrations and 2.6 3.0% between reduced and total plasma cysteine concentrations both in patients and in healthy control subjects. We noted an elevated concentration of total plasma homocysteine in stroke patients, but no difference in the ratio between reduced and total plasma homocysteine concentrations in patients and control subjects (mean value 1.20 and 1.10%, respectively). However, in a subgroup of patients with higher concentrations of total plasma homocysteine, we observed a significantly lower ratio of reduced to total plasma homocysteine compared to a subgroup of patients with lower concentration of total plasma homocysteine. A low reduced/total ratio of plasma homocysteine in combination with elevated plasma homocysteine concentrations might reflect an increased pro-oxidant activity in plasma from these patients. Thus, increased pro-oxidant activity in plasma might be one factor, besides genetic and nutritional factors, that could explain hyperhomocysteinemia. Since substantial evidence indicates that progression of atherosclerosis is related to enhanced pro-oxidant activity, the premature vascular disease associated with increased plasma homocysteine concentration might be as a result of increased pro-oxidant activity and the elevated plasma homocysteine concentration may only reflect the increased oxidative stress.

Aged↗
PubMed2000

Expression and motor effects of secretin in small and large intestine of the rat.

Immunocytochemistry and in situ hybridization revealed abundant secretin expressing cells on duodenal villi with a gradual decrease throughout the small intestines of the rat. They were absent in pancreas, stomach and colon. Secretin caused relaxation of rat intestinal longitudinal muscle in vitro. Studies on colon revealed that the secretin-evoked response was unaffected by apamin, tetrodotoxin, L-NAME, VIP or PACAP pretreatment; secretin itself caused desensitization. Addition of VIP or PACAP when the secretin-evoked relaxation was maximal evoked a further relaxation suggesting the presence of distinct receptors. Secretin causes relaxation via activation of secretin receptors located on the smooth muscle and not via any of the related VIP/PACAP receptors.

Acetylcholine↗
PubMed2000

Cisplatin-induced hearing loss: influence of the mode of drug administration in the guinea pig.

Cisplatin (8 mg/kg) was given intravenously to guinea pigs either as a 15 s bolus injection (25 animals) or as a 1 h infusion (28 animals). To determine the influence of the mode of cisplatin administration and pharmacokinetics on the ototoxic side-effect, the concentrations of cisplatin and the biotransformation product monoaquated cisplatin were determined in blood ultrafiltrate using liquid chromatography with post-column derivatization. Ototoxic effect was evaluated as difference in pre- and 96 h post-exposure auditory brainstem response (ABR) threshold. The cisplatin peak concentration was considerably higher, 19.2+/-2.4 microg/ml, in the bolus injection group than in the infusion group, 6.7+/-0.5 microg/ml (mean+/-S.E.M.). The area under the blood ultrafiltrate concentration time curve (AUC) for cisplatin was slightly greater in the infusion group, 442+/-26 microg/ml/min, than in the bolus injection group, 340+/-5 microg/ml/min. For monoaqua cisplatin, the AUC was not different between the groups (bolus injection: 30.8+/-1. 5 microg/ml/min, infusion: 34.1+/-3.3 microg/ml/min). A significant ototoxic effect was observed in both groups at 20 and 12.5 kHz, but there was no difference between the groups in the extent of threshold shift. The interindividual variability in susceptibility to ABR threshold shift was far greater than the variability in pharmacokinetics, suggesting that other factors are more important in determining the degree of hearing loss.

Animals↗
PubMed2000

Home rehabilitation after stroke. Reviewing the scientific evidence on effects and costs.

OBJECTIVES: The question addressed here is whether home rehabilitation after stroke is better and/or less expensive than the more conventional alternatives, i.e., rehabilitation during inpatient care, day care, and outpatient visits--alone or in combinations appropriate to disease stage and patient needs. Home rehabilitation is managed by teams of professionals who train patients at home. METHODS: The scientific literature was systematically searched for controlled studies comparing outcomes and costs of home rehabilitation with the more conventional strategies. RESULTS: The abstracts of 204 papers were evaluated, from which 89 were selected for greater scrutiny. From the 89 studies, we found 7 controlled studies involving 1,487 patients (6 of the 7 were randomized, 4 of the 6 assessed costs). No statistically significant differences, or tendencies toward differences, were revealed as regards the outcome of home rehabilitation versus hospital-based alternatives. Thus, home rehabilitation was neither better nor worse at improving patients' ability to manage on their own or resume social activities. Depression and reduced quality of life were common in all groups of patients and caregivers, irrespective of the rehabilitation strategy. In the four randomized studies that reported on costs, home rehabilitation was found to be less expensive than regular day care, but not less expensive than conventional strategies even though hospital stay was reduced. CONCLUSION: The outcomes and costs of home rehabilitation after stroke seem to be comparable to alternative treatment strategies.

Ambulatory Care↗
PubMed2000

Concordant xenotransplantation--non-vascularized pancreatic islets are more difficult to regraft than the vascularized heart.

We have previously demonstrated that it is possible to perform retransplantation of a xenogeneic heart (mouse-to-rat) using cyclosporine A as monotherapy, provided that the first heart is transplanted under a short course of deoxyspergualin (DSG). If DSG is omitted, the first heart is rejected within four days and the second heart succumbs to hyperacute rejection within minutes. A mouse heart as first graft does not protect a consecutive pancreatic islet graft, although the heart continues to function after rejection of the cellular graft. One explanation for this discrepancy may be the fact that cellular grafts, as pancreatic islets, lack an endothelial lining. We have, therefore, further investigated possible differences between vascularized and non-vascularized xenografts regarding their capacity to induce unresponsiveness. The use of pancreatic islets as primary graft neither accelerated nor decelerated the speed of rejection of the vascularized heart used as secondary graft. Furthermore, hemagglutinating and cytotoxic antibody titres responded in the same manner as in naive rats transplanted with a mouse heart. Retransplantation with pancreatic islets also resulted in complete rejection of both the primary and secondary grafts. Thus, the lack of unresponsiveness cannot simply be explained by differences, between the pancreatic and cardiac tissues, in antigen expression. In addition, intraperitoneal transplantation of mouse heart cells as primary graft resulted in rejection of a secondary cardiac graft after three days. However, it cannot be totally excluded that the time of antigen exposure had an impact on these results. In conclusion, our previous and present studies suggest that the presence of an intact vascular bed, both in the first and second graft, is necessary to create a state of unresponsiveness. Because the pancreatic islets lack an endothelial lining, they do not benefit from an unresponsiveness of the immune system. Neither are they able to induce such an unresponsiveness.

Animals↗
PubMed2000

Large-scale expression and thermodynamic characterization of a glutamate receptor agonist-binding domain.

The ionotropic glutamate receptors (GluR) are the primary mediators of excitatory synaptic transmission in the brain. GluR agonist binding has been localized to an extracellular domain whose core is homologous to the bacterial periplasmic binding proteins (PBP). We have established routine, baculovirus-mediated expression of a complete ligand-binding domain construct at the 10-L scale, yielding 10-40 milligrams of purified protein. This construct contains peptides that lie outside the PBP-homologous core and that connect the domain core to the transmembrane domains of the channel and to the N-terminal 'X'-domain. These linker peptides have been implicated in modulating channel physiology. Such extended constructs have proven difficult to express in bacteria, but the protein described here is stable and monomeric. Isothermal titration calorimetry reveals that glutamate binding to the domain involves a substantial heat capacity change and that at physiological temperatures, the reaction is both entropically and enthalpically favorable.

Animals↗
PubMed2000

Oxis (formoterol given by Turbuhaler) showed as rapid an onset of action as salbutamol given by a pMDI.

Thirty-six adult patients (16 women) with mild to moderate asthma with a mean baseline forced expiratory volume in 1 sec (FEV1) of 73.8% (46-106%) of predicted normal value and mean reversibility of 24.2% (14.6-47.1%) were included in this double-blind, double-dummy, randomized, placebo-controlled and cross-over study. The patients inhaled single doses 4.5 or 9 microg of formoterol (Oxis) via Turbuhaler salbutamol (Ventolin) 100 or 200 microg from a pressurized metered dose inhaler (pMDI) or placebo at five randomized visits. Efficacy was measured by FEV1 pre-dose and then 1, 3, 5, 7, 10, 15, 20, 25 and 30 min after inhalation of the study drug. The primary variable of efficacy was the FEV1-value 3 min after dose intake. No statistically significant differences were found between active treatments. All active treatments gave a higher bronchodilating effect at 3 min than placebo: 10.0, 11.4% for salbutamol 100 and 200 microg and 11.7, 11.8% for formoterol 4.5 and 9 microg (P<0.001 in all cases). There was a correlation between the measured response at 3 min and the subjective experience of the patients. The relative difference vs. placebo remained throughout the study period for all active treatments except for low dose salbutamol. All treatments were well tolerated. In conclusion, formoterol Turbuhaler has as rapid an onset of action as salbutamol pMDI when given at recommended doses.

Adolescent↗
PubMed2000

Comparison of pesticide residues in composite samples and in individual units: the Swedish approach to sampling.

The method used to take samples for residues testing in Sweden involves taking three subsamples of 1-2 kg. These are split in two for laboratory analyses. Where required one of these laboratory samples can be used to determine the variability between individual units. Details of the variation in residues in individual units of a number of commodities are presented. The highest variability factors, around 600, expressed as the quotient of the maximum and the minimum residue, were found for methamidophos in peppers and monocrotophos in grapes.

Food Analysis↗
PubMed2000

Gender differences in musculoskeletal health of computer and mouse users in the Swedish workforce.

The objectives of the study were to explore the musculoskeletal health of computer users in the Swedish workforce with regard to gender and psychosocial factors, and to describe gender differences between the occupational groups. A subset was chosen from a large survey of 12,462 individuals representing the workforce of Sweden, performed by Statistics Sweden. Included in the subset were 2044 subjects who worked for at least half their working hours with personal computers, or an equivalent device, and also used a computer mouse. All occupational groups had prevalence ratios (women/men) > 1. When using regression models, the variables 'learn and develop' and 'involved in planning your work' were health factors, and 'too much to do' was a risk factor for upper body symptoms for both women and men. For women 'PC duration 100' was a risk factor and 'support from superiors' was a health factor. Age seemed to be a stronger risk factor for men than for women.

Adult↗
PubMed2000

Crystallization of an AMPA receptor binding domain without agonist: importance of carbohydrate content and flash-cooling conditions.

An AMPA-specific ionotropic glutamate receptor binding domain was overexpressed using the baculovirus system and purified by immunoaffinity and metal-affinity chromatography. Purified protein was enzymatically deglycosylated. Both glycosylated and deglycosylated proteins crystallized under the same conditions and in the same space group (P2). In both cases, it was observed that the use of MPD as a cryoprotectant induced a significant reduction in the unit-cell volume compared with glycerol or sucrose. For crystals of deglycosylated protein, cryoprotection with MPD also yielded a dramatic improvement in resolution.

Animals↗
PubMed2000

Fatty acid profile of skeletal muscle phospholipids in trained and untrained young men.

Endurance trained (n = 14) and untrained young men (n = 15) were compared regarding the fatty acid profile of the vastus lateralis muscle after 8 wk on diets with a similar fatty acid composition. The skeletal muscle phospholipids in the trained group contained lower proportions of palmitic acid (16:0) (-12.4%, P < 0.001) and di-homo-gamma-linolenic acid [20:3(n-6)] (-15.3%, P = 0.018), a lower n-6-to-n-3 ratio (-42.0%, P = 0.015), higher proportions of stearic acid (18:0) (+9.8%, P = 0.004) and sum of n-3 polyunsaturated fatty acids (+33.8%, P = 0.009), and a higher ratio between 20:4(n-6) to 20:3(n-6) (+18.4%, P = 0.006) compared with those in the untrained group. The group differences in 16:0, 20:3(n-6), 18:0/16:0, and 20:4(n-6)/20:3(n-6) were independent of fiber-type distribution. The trained group also showed a lower proportion of 16:0 (-7.9%, P < 0.001) in skeletal muscle triglycerides irrespective of fiber type. In conclusion, the fatty acid profile of the skeletal muscle differed between trained and untrained individuals, although the dietary fatty acid composition was similar. This difference was not explained by different fiber-type distribution alone but appears to be a direct consequence of changes in fatty acid metabolism due to the higher level of physical activity.

Adult↗
PubMed2000

Thiol redox status influences extracellular concentration of homocysteine in HeLa cell cultures.

We have recently shown that low concentrations of copper ions increased the extracellular concentration of homocysteine in a HeLa cell culture system. This increase might be attributed to copper-induced oxidation of extracellular homocysteine, since earlier reports suggest that the oxidized fraction of homocysteine seems to be less available for cellular uptake than the reduced fraction. To investigate further this mechanism we have therefore, in the present study, determined intra- and extracellular concentrations of homocysteine and their relations to the extracellular thiol redox status. The results of this study show that the redox status of homocysteine is important for its extracellular concentration. Increased oxidation of thiols catalyzed by copper ions resulted in an increased extracellular concentration of homocysteine, whereas the addition of antioxidant agents (N-acetylcysteine or dithiothreitol) or a specific copper(I) ion chelator (bathocuproinedisulfonic acid) was accompanied by a decreased extracellular concentration of homocysteine. These effects are probably dependent on differences in cellular uptake between reduced and oxidized homocysteine.

Acetylcysteine↗