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Sökning: WFRF:(Holm Ann Charlotte)

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1.
  • Holm, Ann-Charlotte B. Svensson, et al. (författare)
  • Inhibition of 12-lipoxygenase reduces platelet activation and prevents their mitogenic function
  • 2014
  • Ingår i: Platelets. - London, United Kingdom : Informa Healthcare. - 0953-7104 .- 1369-1635. ; 25:2, s. 111-117
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of the present study was to investigate the role of 12-lipoxygenase (12-LOX) on platelet-induced airway smooth muscle cell (ASMC) proliferation. Co-incubation of platelets and ASMC caused platelet activation as determined by morphological changes. Simultaneously, reactive oxygen species (ROS)-generation was detected and ASMC proliferation (measured by using the MTS assay) increased significantly. Furthermore, we found that the 12-LOX inhibitors cinnamyl-3,4-dihydroxy-a-cyanocinnamate (CDC) and Baicalein prevented platelet activation in a co-cultures of platelets and ASMC. The inhibitory effect of CDC and Baicalein on platelets was also registered in a pure platelet preparation. Specifically, the 12-LOX inhibitors reduced collagen-induced platelet aggregation both in the presence and absence of external added fibrinogen. Importantly, platelet-induced ASMC proliferation and ROS production generated during the platelet/ASMC interaction was significantly inhibited in the presence of 12-LOX inhibitors. In conclusion, our findings reveal that 12-LOX is crucial for the observed enhancement of ASMC proliferation in co-cultures of platelets and ASMC. The present result suggests that 12-LOX activity is important in the initial step of platelet/ASMC interaction and platelet activation. Such action of 12-LOX represents a potential important mechanism that may contribute to platelet-induced airway remodelling.
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2.
  • Sodergren, Anna L., et al. (författare)
  • Thrombin-induced lysosomal exocytosis in human platelets is dependent on secondary activation by ADP and regulated by endothelial-derived substances
  • 2016
  • Ingår i: Platelets. - : Taylor & Francis. - 0953-7104 .- 1369-1635. ; 27:1, s. 86-92
  • Tidskriftsartikel (refereegranskat)abstract
    • Exocytosis of lysosomal contents from platelets has been speculated to participate in clearance of thrombi and vessel wall remodelling. The mechanisms that regulate lysosomal exocytosis in platelets are, however, still unclear. The aim of this study was to identify the pathways underlying platelet lysosomal secretion and elucidate how this process is controlled by platelet inhibitors. We found that high concentrations of thrombin induced partial lysosomal exocytosis as assessed by analysis of the activity of released N-acetyl--glucosaminidase (NAG) and by identifying the fraction of platelets exposing the lysosomal-associated membrane protein (LAMP)-1 on the cell surface by flow cytometry. Stimulation of thrombin receptors PAR1 or PAR4 with specific peptides was equally effective in inducing LAMP-1 surface expression. Notably, lysosomal exocytosis in response to thrombin was significantly reduced if the secondary activation by ADP was inhibited by the P2Y(12) antagonist cangrelor, while inhibition of thromboxane A(2) formation by treatment with acetylsalicylic acid was of minor importance in this regard. Moreover, the NO-releasing drug S-nitroso-N-acetyl penicillamine (SNAP) or the cyclic AMP-elevating eicosanoid prostaglandin I-2 (PGI(2)) significantly suppressed lysosomal exocytosis. We conclude that platelet inhibitors that mimic functional endothelium such as PGI(2) or NO efficiently counteract lysosomal exocytosis. Furthermore, we suggest that secondary release of ADP and concomitant signaling via PAR1/4- and P2Y(12) receptors is important for efficient platelet lysosomal exocytosis by thrombin.
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3.
  • Svensson Holm, Ann-Charlotte B., et al. (författare)
  • Hyaluronic acid influence on platelet-induced airway smooth muscle cell proliferation
  • 2012
  • Ingår i: Experimental Cell Research. - San Diego, USA : Elsevier. - 0014-4827 .- 1090-2422. ; 318:5, s. 632-640
  • Tidskriftsartikel (refereegranskat)abstract
    • Hyaluronic acid (HA) is one of the main components of the extracellular matrix (ECM) and is expressed throughout the body including the lung and mostly in areas surrounding proliferating and migrating cells. Furthermore, platelets have been implicated as important players in the airway remodelling process, e.g. due to their ability to induce airway smooth muscle cell (ASMC) proliferation. The aim of the present study was to investigate the role of HA, the HA-binding surface receptor CD44 and focal adhesion kinase (FAK) in platelet-induced ASMC proliferation. Proliferation of ASMC was measured using the MTS-assay, and we found that the CD44 blocking antibody and the HA synthase inhibitor 4-Methylumbelliferone (4-MU) significantly inhibited platelet-induced ASMC proliferation. The interaction between ASMC and platelets was studied by fluorescent staining of F-actin. In addition, the ability of ASMC to synthesise HA was investigated by fluorescent staining using biotinylated HA-binding protein and a streptavidin conjugate. We observed that ASMC produced HA and that a CD44 blocking antibody and 4-MU significantly inhibited platelet binding to the area surrounding the ASMC. Furthermore, the FAK-inhibitor PF 573228 inhibited platelet-induced ASMC proliferation. Co-culture of ASMC and platelets also resulted in increased phosphorylation of FAK as detected by Western blot analysis. In addition, 4-MU significantly inhibited the increased FAK-phosphorylation. In conclusion, our findings demonstrate that ECM has the ability to influence platelet-induced ASMC proliferation. Specifically, we propose that HA produced by ASMC is recognised by platelet CD44. The platelet/HA interaction is followed by FAK activation and increased proliferation of co-cultured ASMC. We also suggest that the mitogenic effect of platelets represents a potential important and novel mechanism that may contribute to airway remodelling. (C) 2011 Elsevier Inc. All rights reserved.
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4.
  • Ljung, Thomas, 1961, et al. (författare)
  • Treatment of abdominally obese men with a serotonin reuptake inhibitor: a pilot study.
  • 2001
  • Ingår i: Journal of internal medicine. - 0954-6820 .- 1365-2796. ; 250:3, s. 219-24
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: To investigate the effects of a selective serotonin reuptake inhibitor (SSRI) on the neuroendocrine and autonomic nervous system perturbations found in abdominal obesity. DESIGN: Treatment for 6 months with citalopram and for 6 months with placebo using a double-blind, cross-over design, with a 2-month wash-out period between treatment periods. SUBJECTS: Sixteen healthy men, 45-60 years, moderately obese and with an abdominal fat distribution. MEASUREMENTS: Anthropometry, three different depression rating scales, serum lipids, testosterone, IGF-I, oral glucose tolerance test (OGTT), pituitary stimulation with corticotropin releasing hormone (CRH), arithmetic stress test, and excretion of cortisol and metoxycatecholamines in urine, collected during 24 h. RESULTS: Cortisol concentrations in the morning were low before treatment, indicating a perturbed function of the hypothalamic-pituitary-adrenal (HPA) axis. After treatment with citalopram morning cortisol concentrations rose to normal. Cortisol concentrations after stimulation with CRH or stress were elevated by citalopram treatment, but urinary cortisol excretion was unchanged. The glucose concentrations after OGTT (120 min) tended to be reduced, with unchanged insulin concentrations, whilst other metabolic values did not change during treatment. Heart rate after administration of CRH, and during laboratory stress test, decreased by treatment with citalopram. Diurnal urinary excretion of metoxycatecholamines tended to decrease. Neither body mass index nor waist/hip circumference ratio decreased. Depression scores were within normal limits before treatment and did not change. CONCLUSION: The results of this pilot study indicate improvements in the regulation of neuroendocrine-autonomic systems as well as metabolism in abdominal obesity during treatment with an SSRI.
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5.
  • Sundman, Ann-Sofie, et al. (författare)
  • Long-term stress levels are synchronized in dogs and their owners
  • 2019
  • Ingår i: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322 .- 2045-2322. ; 9
  • Tidskriftsartikel (refereegranskat)abstract
    • This study reveals, for the first time, an interspecific synchronization in long-term stress levels. Previously, acute stress, has been shown to be highly contagious both among humans and between individuals of other species. Here, long-term stress synchronization in dogs and their owners was investigated. We studied 58 dog-human dyads and analyzed their hair cortisol concentrations (HCC) at two separate occasions, reflecting levels during previous summer and winter months. The personality traits of both dogs and their owners were determined through owner-completed Dog Personality Questionnaire (DPQ) and human Big Five Inventory (BFI) surveys. In addition, the dogs activity levels were continuously monitored with a remote cloud-based activity collar for one week. Shetland sheepdogs (N = 33) and border collies (N = 25), balanced for sex, participated, and both pet dogs and actively competing dogs (agility and obedience) were included to represent different lifestyles. The results showed significant interspecies correlations in long-term stress where human HCC from both summer and winter samplings correlated strongly with dog HCC (summer: N = 57, chi(2) = 23.697, P amp;lt; 0.001, beta = 0.235; winter: N = 55, chi(2) = 13.796, P amp;lt; 0.001, beta = 0.027). Interestingly, the dogs activity levels did not affect HCC, nor did the amount of training sessions per week, showing that the HCC levels were not related to general physical activity. Additionally, there was a seasonal effect in HCC. However, although dogs personalities had little effects on their HCC, the human personality traits neuroticism, conscientiousness, and openness significantly affected dog HCC. Hence, we suggest that dogs, to a great extent, mirror the stress level of their owners.
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6.
  • Svensson Holm, A.-C., et al. (författare)
  • Platelets stimulate airway smooth muscle cell proliferation through mechanisms involving 5-lipoxygenase and reactive oxygen species
  • 2008
  • Ingår i: Platelets. - 0953-7104 .- 1369-1635. ; 19:7, s. 528-536
  • Tidskriftsartikel (refereegranskat)abstract
    • Continuous recruitment and inappropriate activity of platelets in the airways may contribute to airway remodeling, a characteristic feature of inflammatory airway diseases that includes increased proliferation of the smooth muscle. The aim of the present investigation was to examine the effect of platelets on proliferation of airway smooth muscle cells (ASMC) in culture and to determine the possible role of 5-lipoxygenase (5-LOX) and reactive oxygen species (ROS) in this context. ASMC obtained from guinea pigs were cultured and co-incubated with washed platelets for 24 hours. Thereafter, the proliferation was measured with the MTS-assay; the results were also verified by using thymidine incorporation, DNA measurements and manual counting. The interaction between platelets and ASMC was visualized with fluorescence microscopy. We found that platelets bind to the ASMC and the presence of platelets caused a significant dose-dependent increase in ASMC proliferation. Co-incubation of ASMC with platelets also increased ROS-production, detected by the fluorescent probe DCFDA. Furthermore, the platelet-induced proliferation was reduced in the presence of the NADPH-oxidase inhibitors DPI and apocynin. A possible role of 5-LOX in platelet-induced proliferation and ROS-generation was evaluated by using the 5-LOX inhibitor AA-861 and the PLA2-inhibitor ATK. The results showed that inhibition of these enzymes significantly reduced the platelet-induced proliferation. Moreover, Western blot analysis revealed that the ASMC but not the platelets express 5-LOX. In addition, our experiments revealed that the presence of AA-861 and ATK significantly inhibited the ROS-production generated upon co-incubation of platelets and ASMC. In conclusion, we show that platelets have a marked capacity to induce ASMC proliferation. Furthermore, our study indicates that the interaction between platelets and ASMC leads to activation of 5-LOX in the ASMC followed by an increased ROS-production, events resulting in enhanced ASMC proliferation. The new findings are of importance in understanding possible mechanisms contributing to airway remodeling. © 2008 Informa UK Ltd.
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7.
  • Aardal, Elisabeth, et al. (författare)
  • Cortisol in Saliva : Reference Ranges and Relation to Cortisol in Serum
  • 1995
  • Ingår i: European Journal of Clinical Chemistry and Clinical Biochemistry. - 0939-4974. ; 33, s. 927-932
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of this study was to establish morning and evening reference ranges for cortisol in saliva. Another objective was to compare the concentrations of the mainly free cortisol in saliva to those of total cortisol in serum as determined with a commercial radioimmunoassay. The concentrations were determined in matched samples of saliva and serum collected at 8am and 10pm from 197 healthy volunteers. The saliva samples were stable for at least 7 days at room temperature and for 9 months at —20 °C. Reference ranges, the central 95%, were estimated to 3.5—27.0 nmol/1 at 8 am and < 6.0 nmol/1 at 10 pm. The intra-assay coefficient of variation (CV) was below 5% and total CV below 10%. The relation between the cortisol concentrations in serum and saliva was nonlinear with r = 0.86 for serum concentrations < 450 nmol/1 and r = 0.44 for serum concentrations ^ 450 nmol/1. In conclusion, the satisfactory precision of the analysis and the simple non-invasive sampling procedure suggest that saliva may be used for cortisol measurements in situations where blood sampling is difficult to perform.
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8.
  • Aardal-Eriksson, Elisabeth, et al. (författare)
  • Salivary cortisol : an alternative to serum cortisol determinations in dynamic function tests
  • 1998
  • Ingår i: Clinical Chemistry and Laboratory Medicine. - 1434-6621 .- 1437-4331. ; 36:4, s. 215-222
  • Tidskriftsartikel (refereegranskat)abstract
    • Salivary cortisol was measured as an alternative to serum cortisol as a marker for adrenocortical function following insulin tolerance test, corticotropin-releasing-hormone stimulation and adreno-corticotrophic hormone stimulation. During insulin tolerance test and corticotropin-releasing-hormone stimulation adreno-corticotrophic hormone was also measured. The tests were performed on healthy control subjects as well as on patients under investigation for various disturbances in the hypothalamic-pituitary-adrenocortical axis (insulin tolerance test: 3 controls on two occasions and 14 patients; corticotropin-releasing-hormone stimulation: 4 controls and 18 patients; adreno-corticotrophic hormone stimulation: 6 controls and 10 patients). Five patients underwent both insulin tolerance test and corticotropin-releasing-hormone stimulation. Using criteria for adequate cortisol response in serum, the patients were classified as good or poor responders. In 42 of the 45 tests performed the same conclusion as to cortisol status was drawn when based on serum and salivary cortisol responses. In healthy subjects and good responders the mean cortisol relative increase was greater in saliva than in serum in all three tests (p < 0.05). Characteristic of the results for the insulin tolerance test was a significant initial mean decrease (p < 0.05), not found in serum, and the highest observed salivary cortisol value was delayed for at least 30 minutes compared to that in serum. Plasma adreno-corticotrophic hormone correlated significantly with the cortisol concentrations determined 15 minutes later in serum (r = 0.54–0.64) and in saliva (r = 0.76–0.85). The more pronounced cortisol response in saliva than in serum and its closer correlation with adreno-corticotrophic hormone offer advantages over serum cortisol, suggesting salivary cortisol measurement may be used as an alternative parameter in dynamic endocrine tets.
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9.
  • Aardal-Eriksson, Elisabeth, et al. (författare)
  • Salivary cortisol and serum prolactin in relation to stress rating scales in a group of rescue workers
  • 1999
  • Ingår i: Biological Psychiatry. - 0006-3223 .- 1873-2402. ; 46:6, s. 850-855
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Rescue service personnel are often exposed to traumatic events as part of their occupation, and higher prevalence rates of psychiatric illness have been found among this group.Methods: In 65 rescue workers, salivary cortisol at 8 am and 10 pm and serum prolactin at 8 am were related to the psychiatric self-rating scale General Health Questionnaire (GHQ-28) measuring psychiatric health, and the Impact of Events Scale (IES) and Post Traumatic Symptom Scale (PTSS) measuring posttraumatic symptoms.Results: Seventeen percent of the study population scored above the GHQ-28 cut-off limit but none scored beyond the cut-off limit in the IES and PTSS questionnaires. Salivary cortisol concentration at 10 pm correlated with statistical significance to anxiety (p < .005) and depressive symptoms (p < .01) measured with GHQ-28, as well as to posttraumatic symptoms, with avoidance behavior measured with IES (p < .01) and PTSS (p < .005). Two of the rescue workers were followed over time with the same sampling procedure after a major rescue commission.Conclusions: The correlation between evening salivary cortisol and anxiety, depressiveness, and posttraumatic avoidance symptoms indicates that these parameters can be used in screening and follow-up after traumatic stress events.
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10.
  • Holm, Ann-Charlotte (författare)
  • Membrane transport of triiodothyronine : With particular reference to erythrocytes in health and disease
  • 1992
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • Cellular T3 uptake was studied in three human cell systems, i.e. cultured lymphocytes, erythrocytes and erythrocyte membrane vesicles.The basic experimental procedure included 1) incubation of cells or membranes with T3 tracer and increasing concentrations of unlabelled T3, 2) separation of unbound hormone from hormone bound to cells or membranes, 3) counting of radioactivity, and 4) calculation of saturable uptake and uptake constants. Variations on this basic experimental theme included a) addition of ATP or metabolic inhibitors, b) competition by T4 analogues, c) changes of vesicular volume and permeability, and d) changes of membrane temperature. Finally, the T3 concentration in the erythrocytes was measured.The uptake of T3 proved to be carrier-mediated. In lymphocytes it seemed to be energy dependent, but not in erythrocytes, although erythrocyte membrane vesicles had the potential to respond with accelerated uptake to increased energy supply from ATP. The mean Vmax was increased in hyperthyroidism and decreased in hypothyroidism (both p<0.01), and one patient with thyroid hormone resistance had a V max value similar to those of hyperthyroid patients. In patients with low serum free T3 from non-thyroidal causes V max was not altered. The mean Km for T3 uptake in erythrocytes was similar in controls and the patient groups examined.Binding of T3 to the membrane sites occurred only in membranes exposed to 25 °C and subsequently to 0 °C. The mean Bmax thus measured was reduced in hypothyroidism (p<0.05).The mean erythrocyte T3 concentration was 220 pM in healthy subjects, !50 pM in pregnancy, approximately 190 pM in non-thyroidal illnesses and 60 pM in hypothyroidism (all p<0.01).The results show that I) human erythrocytes and lymphocytes take up T3 by carrier-mediated transport, 2) the rate of T3 uptake changes in thyroid diesease but not in pregnancy or nonthyroidal illness, and 3) the erythrocyte T3 concentration is reduced in pregnancy and nonthyroidalillness, as in hypothyroidism.
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