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T Lyberg

Publications and source records attributed to T Lyberg.

At least 19 recordsLinked to original sources
PubMed2006

Activin A inhibits organization of sarcomeric proteins in cardiomyocytes induced by leukemia inhibitory factor.

Cytokine systems are activated in heart failure, and it is believed that interaction between such systems may be important during progression of this disorder. We have previously shown that failing hearts have increased levels of the interleukin-6 related cytokine leukemia inhibitory factor (LIF) and activin A, a member of the transforming growth factor-beta family. The aim of this study was to examine the effects of activin A on cardiomyocytes and a potential interaction with LIF-mediated changes in cell signaling and growth. Cardiomyocytes were isolated from 1- to 3-day-old Wistar rats, and the cells were treated with LIF, activin A or a combination thereof. Our main findings were: (i) activin A treatment reduced the LIF-mediated increase in cardiomyocyte length, perimeter and sarcomeric organization and was accompanied by a substantially decreased alpha-skeletal actin gene expression. (ii) The activin A-mediated phosphorylation of Smad2 was markedly enhanced by LIF. (iii) Activin A markedly induced SOCS3 gene expression, while LIF potently increased the expression of Smad7 mRNA, representing inhibitors of LIF and activin A signaling pathways, respectively. (iv) Inhibiting activation of the Smad2/3 pathway abolished the effects of activin A on LIF-induced changes in cell length, perimeter and sarcomeric organization. In conclusion, activin A markedly attenuates LIF-induced changes in cardiomyocytes, reflecting a potentially important role for both activin A and the Smad2/3 pathway in regulation of myocardial remodeling.

Activins↗
PubMed2006

Homocysteine measurements in geriatric patients.

OBJECTIVE: Homocysteine measurements may be relevant in geriatric medicine as homocysteine has been identified as an independent risk factor for prevalent disorders such as occlusive arterial vascular disease, cognitive impairment and dementia. The aim of the present study was to study diagnostic correlates of plasma total homocysteine (tHcy) in geriatric in-patients. MATERIAL AND METHODS: Blood samples for the analysis of tHcy and related factors like serum vitamin B12, serum folate, red blood cell folate and clinical data were collected from geriatric patients (n=114) in stable clinical condition. RESULTS: Almost 40% of the patients had tHcy values above 20 micromol/L. tHcy correlated significantly with serum folate, serum vitamin B12, serum creatinine and congestive heart failure, but not with red blood cell folate, cerebrovascular disease, coronary heart disease or cognitive impairment. CONCLUSIONS: Hyperhomocysteinaemia seems to be frequent in geriatric patients and might primarily be an indicator of low folate and high creatinine values.

Aged↗
PubMed2005

Increase in plasma calprotectin during long-distance running.

Running leads to biochemical and hematological changes consistent with an inflammatory reaction to tissue injury. We report changes in the plasma concentration of the leukocyte-derived protein calprotectin after long-distance running. Blood samples were collected from runners before and after a marathon, half-marathon, a 30-km cross-country run, a military ranger-training course and short-term maximal physical exercise until exhaustion, VO2max. Leukocyte counts, plasma calprotectin concentration and calprotectin per neutrophilic granulocyte were assayed using a new method. During the marathon, half-marathon, the 30-km run, the ranger-training course and the VO2max exercise, calprotectin levels increased 96.3-fold, 13.3-fold, 20.1-fold, 7.5-fold and 3.4-fold, respectively. These changes may reflect damage to the tissues or vascular endothelium, causing microthrombi with subsequent activation of neutrophils. These cells are known to phagocytose platelets in microthrombi and may contribute to the prevention of clinical thrombosis. The half-life of calprotectin in plasma was about 5 h. The content of calprotectin per neutrophil remained unchanged during exercise at a level similar to that in healthy blood donors: mean: 25 pg/cell, range 18.8-33.6. A reference interval (mean +/- 2 SD) of 18.6-31.4 pg/cell is suggested.

Adult↗
PubMed2005

Leukocyte-platelet interaction in pregnancies complicated with preeclampsia.

OBJECTIVE: Pregnancy is characterized by haemostasis activation, and in preeclampsia endothelial dysfunction, platelet and leukocyte activation are further characteristic features. The aim of this study was to investigate to which extent platelets from normotensive pregnant women or those with preeclampsia are circulating as microparticles or platelet-platelet aggregates. We also investigated if platelet-leukocyte multiconjugates were differently present in nonpregnant and pregnant women. STUDY DESIGN: Using flow cytometry we investigated these parameters in basal samples and after in vitro stimulation with adenosine diphosphate (ADP) or thrombin receptor activation peptide. This was done in samples from 20 matched preeclamptic and normotensive pregnant women and in a group of 12 nonpregnant women. RESULTS: In the basal state we found that women with preeclampsia had a smaller portion of microparticles circulating than the normotensive pregnant women, Upon ADP stimulation both pregnancy groups showed a higher percentage of monocytes and granulocytes with platelets attached and also a higher number of platelets attached to each monocyte and granulocyte than in the group of nonpregnant individuals. CONCLUSION: This article presents further evidence that changes from the nonpregnant to the pregnant state are associated with hemostasis activation as an integrated part of an inflammatory reaction that is even more pronounced when pregnancy is complicated with preeclampsia.

Adenosine Diphosphate↗
PubMed2005

Cardiac fibrinolytic capacity is markedly increased after brief periods of local myocardial ischemia, but declines following successive periods in anesthetized pigs.

BACKGROUND: Fibrinolysis in blood is mainly reflected by the activities of tissue plasminogen activator (tPA) and of plasminogen activator inhibitor-1 (PAI-1). The effect of myocardial ischemia on their activities in the coronary circulation is, however, not established. OBJECTIVES: With an improved experimental model, we therefore examined the effect of a brief period of myocardial ischemia on their activities. Furthermore, the consequences of repeated periods of ischemia, mimicking the situations in patients with unstable angina, were investigated. METHODS: In six anesthetized pigs, we occluded the distal left anterior descending coronary artery (LAD) four times for 10 min with 40 min intervals and determined the activities of tPA and PAI-1 in arterial and coronary venous blood. By simultaneously recording LAD flow, we could estimate cardiac release of these factors at baseline conditions and during reperfusion. RESULTS: Neither net cardiac release of PAI-1 nor alterations in plasma PAI-1 levels were demonstrated during the experiment. However, a significant net release of tPA activity of 10.4 +/- 3.2 IU mL(-1) (P < 0.005) was recorded during baseline conditions. During reperfusion following the first period of ischemia, the cardiac release of tPA activity increased to a peak of 103 +/- 30-fold baseline release, but declined progressively after repeated periods of ischemia. After the fourth period, tPA release did not exceed an estimated baseline accumulation during ischemia and early reperfusion. CONCLUSIONS: In this porcine model, a substantial local increase in fibrinolytic capacity was observed after brief periods of ischemia, but declined subsequently by repeated periods of ischemia.

Angina Pectoris↗
PubMed2004

Long-distance running modulates the expression of leucocyte and endothelial adhesion molecules.

There still exist many unanswered questions whether physical exercise is beneficial or harmful to the immune system. The 'open-window' post-exercise hypothesis states that athletes are more susceptible to infections after exercise, but there is a need for further elucidation. The aim of the present study was to investigate the effect of long-distance running on leucocyte expression of selected adhesion molecules as well as the plasma levels of soluble leucocyte- and endothelium-derived adhesion molecules. Twenty-seven men participating in Oslo marathon together with 16 entrants (eight men and eight women) in the Oslo half-marathon were recruited to this study. Venous blood was collected before and immediately after the races for analysing the leucocyte expression of CD62L, CD11b and CD14 with the help of flow cytometry, and plasma concentrations of soluble (s) sE-selectin, sL-selectin, sP-selectin, sVCAM-1, sICAM-1 and sCD14 were assessed by means of enzyme-linked immunosorbent assays. A significant increase of leucocyte CD11b expression was observed following both races, compared to the pre-race situation. Monocyte CD14 expression increased only after the marathon race. After both races, CD62L expression was significantly lowered on all leucocyte subsets, whereas the plasma levels of sE-selectin, sP-selectin, sL-selectin, sVCAM-1, sICAM-1 and sCD14 were all increased. Altogether, these changes negatively influence the ability of leucocytes to adhere to and actively transmigrate the endothelium to reach the tissues. Our study thus supports the 'open-window' hypothesis, indicating a reduced capacity to combat infectious agents during the immediate post-exercise period.

Adult↗
PubMed2003

Sustained prothrombotic profile after hip replacement surgery: the influence of prolonged prophylaxis with dalteparin.

In a randomized trial on the effect of dalteparin for 5 weeks after HRS we evaluated hemostatic variables in plasma sampled before and 1, 6 and 35 days postoperatively. In 218 patients we found that prothrombin fragment 1 + 2 (F1 + 2), thrombin-antithrombin complexes (TAT), d-dimer and fibrinogen were significantly higher on day 35 as compared with baseline values in the placebo group (P < 0.001 for all). The same pattern was found in the dalteparin group, but with significantly lower values for F1 + 2, TAT and d-dimer. In patients in the placebo group with venographically proven deep vein thrombosis (DVT) on day 35 (33%), significantly higher values were found for F1 + 2, TAT and d-dimer than in patients without DVT. Patients in the highest quartile of d-dimer (>2850 ng mL-1) had an odds ratio for the presence of DVT of 24.0 when compared with patients in the lowest quartile (<1625 ng mL-1). It is concluded that a substantial hypercoagulability is sustained until day 35 after HRS, significantly reduced with prolonged administration of dalteparin.

Aged↗
PubMed2002

Do cardiac glycosides affect platelet function? A flow cytometric study in healthy volunteers.

OBJECTIVE: Cardiac glycosides exert their inotropic effect by increasing intracellular calcium. Increased intracellular calcium is a key event in platelet aggregation. In aggregometer studies, digitalis has been found to augment platelet agonist responses. A prothrombotic effect of digitalis might be concealed since heart failure and atrial fibrillation per se predispose to thromboembolism. The present study investigates the effects of digitoxin on platelet function in healthy volunteers. METHODS: Twenty healthy, non-smoking volunteers were randomised to receive digitoxin ( n = 10, 0.6 mg day 1, 0.4 mg day 2, then 0.1 mg daily) or placebo ( n = 10) for 10 days. Platelet function was then analysed ex vivo using three-colour whole-blood-flow cytometry, both in non-stimulated mode and after agonist stimulation with 0.1 micromol/l adenosine diphosphate (ADP), 10 micromol/l ADP and 5.0 micromol/l epinephrine (final concentrations). Expression of activated fibrinogen receptor, von Willebrand's factor receptor and P-selectin, formation of platelet-platelet and platelet-leukocyte aggregates and particle size were examined. RESULTS: No significant difference between the placebo and the digitoxin group (digitoxin levels 17-42 nmol/l) was found, neither on a global level nor for any isolated parameter. CONCLUSIONS: Theory and in vitro data suggest that digitoxin treatment could activate platelets. No evidence for this was found in healthy volunteers. This observation is strengthened by the unequivocal results for all parameters measured. However, thrombosis-prone patients with heart failure and/or atrial fibrillation may respond differently to digitalis therapy.

Adult↗
PubMed2002

Leukotriene antagonism reduces the generation of endothelin-1 and interferon-gamma and inhibits eosinophilic airway inflammation.

The cysteinyl leukotrienes (cysLTs) and the peptide hormone endothelin (ET)-1 are potent bronchoconstrictor substances, and these mediators are also claimed to be implicated in the development of eosinophilic airway inflammation. In the present study, we have investigated the effect of the cysLT1 receptor antagonist montelukaston the development of an eosinophilic airway inflammation 24 h after intratracheal Sephadex (SDX) provocation in rats. Furthermore, the effect of montelukast treatment on the generation of ET-1 and other pro-inflammatory mediators has been studied. The inflammatory response was significantly reduced in the animals receiving SDX + montelukast compared to animals receiving solely SDX, as evaluated by a decrease in bronchoalveolar lavage fluid total cell count (10.3 +/- 1.2 vs. 18.5 +/- 1.8 x 10(4) ml(-1), P<0.001), number of eosinophils (299.7 +/- 43.8 vs. 577.6 +/- 46.6 x 10(2) ml(-1), P<0.001), and lymphocytes (116.8 +/- 20 vs. 222.0 +/- 34.8 x 10(2) ml(-1), P<0.05), as well as the degree of tissue inflammation (P<0.05). Montelukast also inhibited the increase in the concentration of the pro-inflammatory mediators ET-1 (28.5 +/- 75 vs. 40.9 +/- 7.3 x pg ml(-1), P<0.05) and interferon (IFN)-gamma (4.3 +/- 2.2 vs. 15.6+/-8.7 x pg ml(-1), P<0.05), but not tumor necrosis factor-gamma or interleukin-8. In summary, treatment with the cysLT1 receptor antagonist montelukast reduced the inflammatory response during development of an eosinophilic airway inflammation, possibly by inhibiting the release of pro-inflammatory mediators like ET-1 and IFN-gamma.

Acetates↗
PubMed2002

Reactive oxygen species generation by leukocytes in populations at risk for atherosclerotic disease.

The aim of this study was to investigate intracellular levels of reactive oxygen species (ROS) in circulating leukocytes in populations at risk for atherosclerosis compared with in healthy individuals. The study populations consisted of 27 non-diabetic men (aged 40-69 years) with untreated hypercholesterolemia (HC), 13 individuals (aged 39-56 years) with well-controlled insulin-dependent diabetes mellitus (DM), and 20 healthy individuals (aged 26-61 years) (REF). Citrated whole blood was collected in fasting condition. Using flow cytometric techniques, the resting levels and the response upon phorbol 12-myristate 13-acetate (PMA, 100 ng/mL) stimulation of ROS were measured in circulating monocytes (MO) and granulocytes (GR). The relative mean fluorescence intensity (rMFI) in 10(4) leukocytes of fluorochromes mainly reflecting the levels of peroxynitrite (ONOO-) hydrogen peroxide (H2O2) and superoxide anion (O2-) was recorded. Significantly, higher basal levels of ONOO- in GR from the combined risk population compared with REF were found (1.4 vs. 1.5 rMFI, p<0.05). Upon PMA stimulation, significantly lower levels of O2 in GR in the risk populations compared to REF (119 vs. 90 Si, p<0.001) were observed. In conclusion, increased resting levels of ROS in circulating granulocytes, but reduced response to PMA stimulation could be demonstrated in populations at risk for atherosclerosis compared with in healthy individuals. This might indicate a higher degree of resting oxidative reactions, with partly exhausted cells and less capacity to host defence.

Adult↗
PubMed2001

Outer membrane vesicles from Neisseria meningitidis: effects on tissue factor and plasminogen activator inhibitor-2 production in human monocytes.

Lipopolysaccharide-containing outer membrane vesicles (OMV-LPS) which are spontaneously released from Neisseria meningitidis during logarithmic growth were studied for their ability to induce procoagulant (tissue factor), profibrinolytic (urokinase-type plasminogen activator) and antifibrinolytic (plasminogen activator inhibitor-2) factors in purified human monocytes. Cell-associated tissue factor was 5.0-fold (n=5) increased, peaking after 8 h, in the presence of OMV-LPS (1 microg/ml, final concentration). Plasminogen activator inhibitor-2 release from monocytes was maximal after 24 h OMV-LPS (1 microg/ml) stimulation and 13.7-fold (n=5) increased compared to controls; whereas urokinase-type plasminogen activator antigen in culture medium remained uninfluenced by OMV-LPS. In conclusion, these OMV-induced imbalances favor fibrin deposition in the monocyte microenvironment and is probably of great importance in the development of disseminated intravascular coagulation, microthrombosis and organ dysfunction related to fulminant meningococcal septicemia.

Cell Membrane↗
PubMed2001

Outer membrane vesicles from Neisseria meningitidis: effects on cytokine production in human whole blood.

The Norwegian group B meningococcal outer membrane vesicle (OMV) vaccine consists of outer membrane proteins (OMPs) as main antigens with significant amounts of lipopolysaccharide (LPS; 5-9% relative to protein). We have studied the ability of this OMV vaccine preparation to induce secretion of pro-inflammatory cytokines, tumour necrosis factor alpha (TNF-alpha), interleukin 1beta (IL-1beta), interleukin 6 (IL-6), interleukin 8 (IL-8) and anti-inflammatory cytokines, interleukin 4 (IL-4), interleukin 10 (IL-10) and interleukin 13 (IL-13) in a human whole blood model. Plasma levels of TNF-alpha, IL-1beta, IL-6 and IL-8 were massively increased; mean peak levels of TNF-alpha 44 696+/-7764, IL-1beta 38 043+/-5411, IL-6 10 057+/-1619 and IL-8 30 449+/-5397 pg/ml were obtained with an OMV-LPS concentration of 1 microg/ml; corresponding levels in control plasmas were below the detection limit of the assay. Mean maximal level of IL-10 (2540+/-144 pg/ml) was obtained at OMV-LPS concentration of 10 microg/ml, after 24 h; while the level in control plasma was below detection limit. OMV-LPS did not induce release of IL-4 and IL-13 in doses from 0.001-10 microg/ml. The present results show that OMVs from meningococci have potent pro-inflammatory properties and are likely to contribute to the observed local and systemic inflammatory effects.

Bacterial Outer Membrane Proteins↗
PubMed2001

Obstructive sleep apnea: a canonical correlation of cephalometric and selected demographic variables in obese and nonobese patients.

One hundred male obstructive sleep apnea (OSA) patients were classified into 2 groups on the basis of body mass index (BMI): 43 nonobese (BMI < 30 kg/m2) and 57 obese (BMI > or = 30 kg/m2) patients. A comprehensive cephalometric analysis with a multivariate statistical method was performed in order to define the different principal components (PCs) of cervico-craniofacial skeletal and upper airway soft tissue morphology in each group and how they contributed to selected elements of the patient demographic data, ie, apnea-hypopnea index (AHI), nocturnal oxyhemoglobin saturation, and BMI. Thirty cephalometric variables of cervico-craniofacial skeletal morphology were reduced to 8 PCs describing 84.4% and 85.4% of the total variance in obese and nonobese OSA patients, respectively. Sixteen cephalometric variables of hyoid bone position and head posture were reduced to 4 PCs describing 84.4% and 85.9% of the total variance in obese and nonobese OSA patients, respectively. Twenty cephalometric variables of upper airway soft tissue morphology were reduced to 7 PCs describing 89.5% and 84.6% of the total variance in obese and nonobese OSA patients, respectively. For further analysis of PCs, a stepwise multiple regression analysis was chosen. Two dependent variables of interest are the minimal distance of the posterior pharyngeal airway space (PASmin) and AHI. PASmin accounted for 95.3% (obese OSA group) and 74.3% (nonobese OSA group) with 7 PCs and AHI for 46% with 3 PCs in both groups. Three canonical variables and their correspondents with different loadings were established differently for both OSA groups. A canonical correlation successfully clarified the complexity of simultaneous relationship of the relevant variables. These analyses are proved useful to demonstrate the relationship of cervico-craniofacial skeletal and upper airway soft tissue morphology and selected demographic data. This lays down a basis for understanding the complicated pathogenic components of obese and nonobese OSA patients.

Adult↗
PubMed2001

Factors influencing the predictability of soft tissue profile changes following mandibular setback surgery.

The objective of this cephalometric study was to assess long-term changes in the soft tissue profile following mandibular setback surgery and investigate the presence of factors that may influence the soft tissue response to skeletal repositioning. The subjects enrolled were 80 consecutive mandibular prognathism patients operated with bilateral sagittal split osteotomy and rigid fixation. Lateral cephalograms were taken at 6 occasions: immediate presurgical, immediate postsurgical, 2 and 6 months postsurgical, and 1 and 3 years postsurgical. The subjects were grouped according to gender and magnitude of setback. Ratios of soft tissue to hard tissue movements were calculated for the subgroups. Females generally demonstrated greater ratios than males with a statistically significant difference for the upper lip and chin (P < .05). Postsurgical alterations in the profiles were more predictable in patients with larger setbacks compared to patients with smaller ones. Skeletal relapse had a profound influence on long-term profile changes. Based on these findings, it is proposed that the database used in prediction software be adjusted to account for such factors in an attempt to improve the accuracy of computerized treatment simulations.

Adult↗
PubMed2001

Mandibular advancement surgery in high-angle and low-angle class II patients: different long-term skeletal responses.

The objective of this cephalometric study was to compare skeletal stability and the time course of postoperative changes in high-angle and low-angle Class II patients after mandibular advancement surgery. The subjects were 61 consecutive mandibular retrognathism patients whose treatment included bilateral sagittal split osteotomy and rigid fixation. The patients were divided according to the preoperative mandibular plane angle; the 20 patients with the lowest mandibular plane angle (20.8 degrees +/- 4.9 degrees ) constituted the low-angle group, while the 20 cases with the highest mandibular plane angle (43.0 degrees +/- 4.0 degrees ) represented the high-angle group. Lateral cephalograms were taken on 6 occasions: immediately before surgery, immediately after surgery, 2 and 6 months after surgery, and 1 and 3 years after surgery. Results demonstrated that the high-angle and low-angle groups had different patterns of surgical and postoperative changes. High-angle patients were associated with both a higher frequency and a greater magnitude of horizontal relapse. While 95% of the total relapse took place during the first 2 months after surgery in the low-angle group, high-angle patients demonstrated a more continuous relapse pattern, with a significant proportion (38%) occurring late in the follow-up period. Possible reasons for the different postsurgical response are discussed.

Adolescent↗
PubMed2001

Soft tissue profile changes following mandibular advancement surgery: predictability and long-term outcome.

The objectives of this cephalometric study were to assess long-term changes in the soft tissue profile following mandibular advancement surgery and to investigate the relationship between soft tissue and hard tissue movements. The sample consisted of 61 patients treated consecutively for mandibular retrognathism with orthodontic therapy combined with bilateral sagittal split osteotomy and rigid fixation. Lateral cephalograms were taken on 6 occasions: immediately before surgery, immediately after surgery, 2 and 6 months after surgery, and 1 and 3 years after surgery. Postsurgical changes in the upper and the lower lips and the mentolabial fold were more pronounced among low-angle cases compared with high-angle cases. In accordance with other studies, the soft tissue chin and the mentolabial fold were generally found to follow their underlying skeletal structures in a 1:1 ratio. Because of the strong influence skeletal relapse has on soft tissue profile changes, alternative ratios of soft tissue-to-hard tissue movement that accounted for mean relapse were also generated. It is suggested that if a more realistic long-term prediction of the postsurgical soft tissue profile is desirable, then ratios incorporating mean relapse should be used rather than estimates based on a 1:1 relationship.

Adolescent↗
PubMed2001

Contact sensitivity reactions in the oral mucosa.

Although the role of T cells in skin contact sensitivity (CS) immune reactions has been intensely studied, much less is known about the regulatory properties of T cells in the oral mucosa. Animal experiments have shown that hapten sensitization of the ectodermal oral mucosa leads to antigen-specific hypersensitivity reactions in the skin. Furthermore, oral mucosa or skin hapten sensitization resulted in CS inflammatory reactions in the oral mucosa on challenge. The oral mucosa CS responses were similar to those found skin with regard to cell phenotypes and cytokines. CS-like reactions were also found in the oral mucosa after exposure to an irritant detergent, sodium lauryl sulfate (SLS). The oral mucosa reacted at smaller SLS doses than did skin. Ions and molecules released fron dental restorative materials (together with saliva and food and/or beverages) expose the gastrointestinal mucosa continuously over long time periods. From animal experiments we have learned that mice given antigen by gastric feeding, subsequently antigen-sensitized on skin, and finally elicited in the oral mucosa and in ear skin, showed tolerance in skin but gave simultaneous CS inflammatory reactions in the oral mucosa. Moreover, exposure of colon mucosa to antigen produced CS reactions in oral mucosa after challenge. Are there CS reactions in the oral mucosa? Clinical and experimental studies indicate that the oral mucosa can function both as induction and expression site of CS. The GI tract may be an important modifier of the CS inflammatory reactions seen in the oral mucosa.

Adjuvants, Immunologic↗