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Milovanovic, Micha
Publications (10 of 20) Show all publications
Milovanovic, M., Nilsson, S., Harakka, P., Post, C. & Gerlde, B. (2016). High in vivo platelet activity in female fibromyalgia patients. Journal of Biomedical Sciences, 5(3:21), 1-5
Open this publication in new window or tab >>High in vivo platelet activity in female fibromyalgia patients
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2016 (English)In: Journal of Biomedical Sciences, ISSN 2254-609X, Vol. 5, no 3:21, p. 1-5Article in journal (Refereed) Published
Abstract [en]

Introduction: Fibromyalgia (FMS) is a pain syndrome characterized by chronic widespread pain and hyperalgesia/allodynia. Many affected are women and risk factors are unidentified. Today, a certain number of set criteria of disease signs and symptoms must be met for the diagnosis to be made. These criteria are used because of the lack of reliable biomarkers or other medical examination. The current study examines if in vivo platelet activity varies between FMS and controls without FMS.

Material and Methods: The study involves 24 females (age 38 + 9 (SD) years) with diagnosed FMS. 25 healthy females (age 50 + 12 (SD) years) without FMS served as controls. After sampling the whole platelet population was separated according to density with a linear Percoll™, into 17 density fractions. Platelet counts was carried out in all fractions using a routine cell counter. In addition, a flow cytometer was used to measure platelet bound fibrinogen without platelet agonist, reflecting in vivo platelet activity.

Results: The study groups did not differ with respect to the distribution of platelets in the gradient. FMS sufferers demonstrated a significant higher platelet bound fibrinogen in most of the platelet density fractions. In particular, significant differences (p < 0.05) were obtained in fractions numbers 2-14 and 16. In difference, fractions numbers 1, 15 and 17 did not show any significant variance.

Discussion: This is the first study to examine in vivo platelet activity in FMS. The results indicate that FMS is associated with elevated in vivo platelet activity compared to individuals without FMS. The clinical significance and the biochemical mechanisms regarding platelet heterogeneity are still uncertain. The results stimulate further research to elucidate the importance of platelet diversity in FMS

Place, publisher, year, edition, pages
iMedPub, 2016
Keywords
Fibromyalgia; Fibrinogen; Platelets; Platelet activity; Platelet heterogeneity
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:liu:diva-130641 (URN)10.4172/2254-609X.100035 (DOI)
Available from: 2016-08-19 Created: 2016-08-19 Last updated: 2018-03-20
Järemo, P., Eriksson-Franzen, M., Oweling, M. & Milovanovic, M. (2016). Platelets and inflammatory parameters do not affect long-term survival after acute stroke. Journal of Stroke and Cerebrovascular Diseases,. Journal of Stroke & Cerebrovascular Diseases, 25(8), 1936-1938
Open this publication in new window or tab >>Platelets and inflammatory parameters do not affect long-term survival after acute stroke. Journal of Stroke and Cerebrovascular Diseases,
2016 (English)In: Journal of Stroke & Cerebrovascular Diseases, ISSN 1052-3057, E-ISSN 1532-8511, Vol. 25, no 8, p. 1936-1938Article in journal (Refereed) Published
Abstract [en]

Rationale

According to literature, the inflammatory response and platelets are associated with coronary heart disease mortality. In this study, we examine if similar relationships exist after acute cerebral infarctions.

Design

Between 2005 and 2007, individuals (n = 61) hospitalized with acute stroke were investigated 2.1 ± .3 (SD) days after hospital admission. After 9.3 ± .7 (SD) years, 29 patients (age 79 ± 8 [SD]; 12 women) had died. They were compared with survivors (age 69 ± 9 [SD]; 9 women) with respect to inflammatory parameters and platelet features such as activity and reactivity.

Results and conclusion

Inflammation and platelets at the acute event do not forecast long-term survival of stroke sufferers

National Category
Neurology
Identifiers
urn:nbn:se:liu:diva-130637 (URN)10.1016/j.jstrokecerebrovasdis.2016.04.022 (DOI)000380937700025 ()
Note

Funding agencies: Bristol-Myers Squibb; Stahls Foundation; Swedish Stroke Foundation; Medical Research Council of Southeast Sweden

Available from: 2016-08-19 Created: 2016-08-19 Last updated: 2018-03-23
Järemo, P., Eriksson-Franzen, M. & Milovanovic, M. (2015). Platelets, gender and acute cerebral infarction. Journal of Translational Medicine, 13(267)
Open this publication in new window or tab >>Platelets, gender and acute cerebral infarction
2015 (English)In: Journal of Translational Medicine, ISSN 1479-5876, E-ISSN 1479-5876, ISSN ISSN 1479-5876, Vol. 13, no 267Article in journal (Refereed) Published
Abstract [en]

Objective

Platelets may well be significant in the pathogenesis of cerebral infarction. Platelets vary substantially according to gender. The scope of our current work is to establish if female and male stroke sufferers differ regarding platelet reactivity.

Patients and methods

73 Consecutive individuals stricken by acute ischemic cerebral infarction (31 females, 42 males) participated. All stroke subtypes were included. Platelet counts was determined electronically. Platelet reactivity i.e. the presence of surface-bound fibrinogen following provocation was analyzed with a flow cytometer. ADP (1.7 μmol/L) and a thrombin receptor agonist (TRAP-6) (57 μmol/L) were the agonists used.

Results

Female stroke sufferers had higher platelet counts (p = 0.013) but their platelets were less reactive. The p values were (p = 0.038) and (p = 0.016) for ADP and TRAP-6, respectively.

Conclusion

The current study demonstrates that women suffering acute cerebral infarction have less reactive platelets. It is concluded that gender affects platelets. Our study indicates that it may be beneficial to individualize platelet inhibition of stroke sufferers according to gender.

Place, publisher, year, edition, pages
BioMed Central, 2015
National Category
Clinical Laboratory Medicine
Identifiers
urn:nbn:se:liu:diva-120697 (URN)10.1186/s12967-015-0630-x (DOI)
Available from: 2015-08-21 Created: 2015-08-21 Last updated: 2017-12-04Bibliographically approved
Milovanovic, M., Eriksson, K., Winblad, B., Nilsson, S., Lindahl, T., Post, C. & Järemo, P. (2014). Alzheimer and platelets: Low-density platelet populations reveal increased serotonin content in Alzheimer type dementia. Clinical Biochemistry, 47(15), 51-53
Open this publication in new window or tab >>Alzheimer and platelets: Low-density platelet populations reveal increased serotonin content in Alzheimer type dementia
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2014 (English)In: Clinical Biochemistry, ISSN 0009-9120, E-ISSN 1873-2933, Vol. 47, no 15, p. 51-53Article in journal (Refereed) Published
Abstract [en]

Introduction: Alzheimers disease (AD) is a progressive form of dementia characterized by an increase in the toxic substance beta-amyloid in the brain. Platelets display a substantial heterogeneity with respect to density. They further contain a substantial amount of beta-amyloid precursor protein. Platelets take up and store serotonin (5-HT) that plays an important role in the pathogenesis of severe depression. The current study aims to investigate platelet serotonin content in different platelet density populations. Material and methods: The study involved 8 patients (age 70 +/- 8 (SD) years) (3 females/5 males) with moderate AD. 6 healthy elderly subjects (age 66 +/- 9 (SD) years) (3 females/3 males) served as controls. The platelet population was divided into 17 subpopulations according to density, using a linear Percoll (TM) gradient. Platelets were counted in all fractions. After cell lysis an ELISA technique was employed to determine the 5-HT content in each platelet subfraction. Results: The two study groups did not differ significantly regarding platelet distribution in the gradients, but AD sufferers have a significantly higher 5-HT content (p less than 0.05) in the lighter platelet populations. Discussion: AD-type dementia proved to be associated with lighter platelets containing more 5-HT. It is possible that platelets from AD patients release less 5-HT. It is speculated that AD synapses are affected in a manner comparable to platelets, which could explain why 5-HT reuptake inhibitors are less effective in AD dementia.

Place, publisher, year, edition, pages
Elsevier, 2014
Keywords
Alzheimers disease; Fibrinogen; Platelets; Platelet activity; Platelet density; Platelet heterogeneity; Serotonin
National Category
Basic Medicine Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-111746 (URN)10.1016/j.clinbiochem.2014.07.007 (DOI)000342822100008 ()25041722 (PubMedID)
Note

Funding Agencies|Ahlens Foundation; Gun and Bertil Stohnes Foundation; Magnus Bergvalls Foundation; "Stiftelsen for Gamla Tjanarinnor"; Swedish Alzheimer Foundation; Swedish Board for Health and Welfare; Pfizer AB, Sweden

Available from: 2014-10-31 Created: 2014-10-31 Last updated: 2018-01-11Bibliographically approved
Järemo, P., Milovanovic, M., Buller, C., Nilsson, S. & Winblad, B. (2013). Alzheimer's disease and granulocyte density diversity. European Journal of Clinical Investigation, 43(6), 545-548
Open this publication in new window or tab >>Alzheimer's disease and granulocyte density diversity
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2013 (English)In: European Journal of Clinical Investigation, ISSN 0014-2972, E-ISSN 1365-2362, Vol. 43, no 6, p. 545-548Article in journal (Refereed) Published
Abstract [en]

BACKGROUND:

The current study investigates circulating eosinophils and neutrophils in Alzheimer's (AD) type dementia with respect to density (kg/L). The existence of β-amyloid plaques in the brain is a feature of AD. Sporadic scientific reports indicate that the disease affects circulating neutrophils. In contrast, numerous publications investigate inflammatory reactions in AD brains. Locally, the plaques evoke a substantial inflammatory response involving activated microglia and astrocytes.

METHODS:

Subjects with probable AD (n = 39) were included and compared with elderly individuals (n = 22) lacking apparent memory problems. We sampled 10 mL venous blood in citrate. Granulocytes were separated according to density in linear Percoll™ gradients. Subsequently, the gradients were divided into density subfractions (n = 16). In every fraction, determination of eosinophil and neutrophil counts was carried out.

RESULTS:

AD sufferers displayed less granulocytes in fractions nos. 13-15 containing light cells. For these fractions, the P-values proved to be (P < 0·001; not significant; P = 0·03) and (P = 0·01; P = 0·01; not significant), for eosinophils and neutrophils, respectively.

CONCLUSIONS:

The present work describes that less circulating light granulocytes are a feature of AD demented individuals. It is to hypothesize that it is a sign of impaired granulocyte turnover and cell damage. It is concluded that AD affects inflammatory cells in the periphery and that the behaviour of granulocytes in dementia is worthwhile further studies.

Place, publisher, year, edition, pages
John Wiley & Sons, 2013
National Category
Other Medical Sciences Basic Medicine
Identifiers
urn:nbn:se:liu:diva-91733 (URN)10.1111/eci.12072 (DOI)000318813100001 ()23551244 (PubMedID)
Available from: 2013-04-30 Created: 2013-04-30 Last updated: 2018-01-11
Järemo, P., Eriksson, M., Lindahl, T., Nilsson, S. & Milovanovic, M. (2013). Platelets and acute cerebral infarction. Platelets, 24(5), 407-411
Open this publication in new window or tab >>Platelets and acute cerebral infarction
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2013 (English)In: Platelets, ISSN 0953-7104, E-ISSN 1369-1635, Vol. 24, no 5, p. 407-411Article in journal (Refereed) Published
Abstract [en]

Stroke is worldwide a leading cause of death and disability. Its etiology is regarded as heterogeneous. Platelets are implicated in its pathophysiology, but our understanding of their specific role is incomplete. Only sparse and conflicting information exists about platelet reactivity and activity in acute stroke. Some scientists take the view that platelets activate in conjunction with acute cerebral infarctions. Others put forward evidence corroborating the contrary notion. Increased soluble P-selectin as a sign of platelet and/or endothelial activity seems to be a feature of the disease. The latter point of view is opposed by other researchers. Due to these conflicting opinions, this study is devoted to platelet characteristics in acute cerebral infarctions. We studied subjects (n = 72; age 74 +/- 10(SD) years; 31 females) having acute stroke. As controls served atrial fibrillation (AF) patients (n = 58; age 69 +/- 7(SD) years; 12 females) subject to electrical cardioversion, a flow cytometer was put to use for measuring platelet reactivity and activity. After agonist provocation, both platelet bound P-selectin and fibrinogen were employed as estimates of platelet reactivity. Dilutions of a thrombin-receptor-activating peptide (TRAP-6) (74 and 57 mmol/l) (P-selectin and fibrinogen) and ADP (8.5 and 1.7 mmol/l) (fibrinogen only) were put to use as platelet agonists. Membrane-bound P-selectin without agonist stimulation served as a measure of in vivo platelet activation. Soluble P-selectin, as determined from a commercial ELISA, was used to assess platelet and/or endothelial activity. In acute stroke neither platelet-bound P-selectin nor fibrinogen after stimulation, i.e. reactivity, differed from AF controls. In contrast, lower platelet activity as judged from surface attached and circulating P-selectin without agonist stimulation proved to be a feature of cerebral infarctions. The p-values were p < 0.001 and p < 0.01, respectively. It is concluded that acute stroke is not associated with platelet reactivity platelets circulate less activated during the disease. It is evident that the mechanisms reflecting platelet reactivity and activity being investigated in this study play minor roles in stroke pathophysiology. New powerful platelet inhibitory drugs are currently introduced. To avoid major bleeding studies on platelet, behavior in acute stroke are necessary before including these medications in stroke treatment protocols.

Place, publisher, year, edition, pages
Informa Healthcare, 2013
Keywords
Flow cytometry, platelet activation, platelet reactivity, platelets, P-selectin
National Category
Basic Medicine
Identifiers
urn:nbn:se:liu:diva-91735 (URN)10.3109/09537104.2012.712168 (DOI)000321065000011 ()22891819 (PubMedID)
Available from: 2013-04-30 Created: 2013-04-30 Last updated: 2018-01-11
Järemo, P., Milovanovic, M., Buller, C., Nilsson, S. & Winblad, B. (2013). P-selectin paradox and dementia of the Alzheimer type: Circulating P-selectin is increased but platelet-bound P-selectin after agonist provocation is compromised. Scandinavian Journal of Clinical and Laboratory Investigation, 73(2), 170-174
Open this publication in new window or tab >>P-selectin paradox and dementia of the Alzheimer type: Circulating P-selectin is increased but platelet-bound P-selectin after agonist provocation is compromised
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2013 (English)In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 73, no 2, p. 170-174Article in journal (Refereed) Published
Abstract [en]

Objective. Knowledge concerning the neurobiological importance of platelets in Alzheimers disease (AD) is sparse. P-selectin, which is located together with beta-amyloid precursor proteins in platelet alpha-granules, is also found in endothelial cells. Upon activation, P-selectin is relocated to cell surfaces where it acts as a receptor. Subsequently, the protein is cleaved from the membrane, to then be circulated. We investigated P-selectin behavior in AD dementia. Methods. We recruited 23 persons diagnosed moderate AD and 17 healthy elders without obvious memory problems. Circulating P-selectin was analyzed using an ELISA technique and flow cytometry was used to measure surface-bound P-selectin. The latter measure was carried out without provocation (platelet activity) and after in vitro agonist stimulation (platelet reactivity). A thrombin-receptor activating peptide (TRAP-6) (74 mu mol/L)) was used as a platelet agonist. Results. Soluble P-selectin was augmented in AD (p = 0.019) but platelet membrane-attached P-selectin did not differ from controls. AD diagnosis was associated with less surface-bound P-selectin after provocation. Significant results were obtained when 74 mu mol/L TRAP-6 was used as a platelet agonist (p = 0.0008). Conclusion. This study describes apparently paradoxical P-selectin reactions in moderate AD. While soluble P-selectin was higher in the disease group, membrane-attached P-selectin without agonist stimulation was no different between the disease and control groups. In contrast, AD was linked to lower platelet reactivity. The current findings encourage further research into this P-selectin paradox and its relevance for AD and, perhaps, other types of dementia as well.

Place, publisher, year, edition, pages
Informa Healthcare, 2013
Keywords
Alzheimers disease, endothelium, platelet activity, platelet reactivity, P-selectin
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-90754 (URN)10.3109/00365513.2013.764572 (DOI)000315896000012 ()23421771 (PubMedID)
Note

Funding Agencies|Swedish Board for Health and Welfare||Pfizer AB, Sweden||Ahlens Foundation||Gun and Bertil Stohnes Foundation||

Available from: 2013-04-05 Created: 2013-04-05 Last updated: 2017-12-06
Järemo, P., Milovanovic, M., Buller, C., Nilsson, S. & Winblad, B. (2012). Low-density platelet populations demonstrate low in vivo activity in sporadic Alzheimer disease. Platelets, 23(2), 116-120
Open this publication in new window or tab >>Low-density platelet populations demonstrate low in vivo activity in sporadic Alzheimer disease
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2012 (English)In: Platelets, ISSN 0953-7104, E-ISSN 1369-1635, Vol. 23, no 2, p. 116-120Article in journal (Refereed) Published
Abstract [en]

Platelets contain a substantial quantity of amyloid-precursor protein (APP) and β-amyloid. However, despite the large importance of APP and β-amyloid to dementia, little is known about platelets in sporadic Alzheimer dementia (AD). Furthermore, platelet heterogeneity influences human pathology and has been described to affect the progression of AD. This study investigated AD platelets with respect to density diversity and in vivo activity associated with density sub-fractions. We included 39 AD patients and used, as controls, 22 elderly individuals without apparent memory disorder. A continuous Percoll™ gradient covering the density span 1.04–1.09 kg/l provided the basis to divide platelets of whole blood into density fractions (n = 16). All platelet populations were evaluated accordingly. Platelet counts were determined electronically. A flow-cytometer was put to use to measure surface-bound fibrinogen as a measure of platelet in vivo activity. Samples obtained from patients diagnosed with sporadic AD contained platelets (fractions numbers 4–16) that circulated with significantly less surface-bound fibrinogen, i.e., their platelet activation in vivo was reduced, compared with controls. In particular, highly significant differences (p < 0.001) were obtained for the six less dense platelet populations (fractions numbers 11–16) when comparing sporadic AD with controls. In contrast, the densest AD platelets in fractions numbers 1–3 did not differ significantly from control cells with respect to in vivo platelet-bound fibrinogen. It is concluded that sporadic AD is characterized by lower density platelet populations that, while circulating, exhibited reduced activation. The clinical significance of this finding is unclear but these results suggest the importance of platelet heterogeneity in dementia as a topic for further investigation.

Place, publisher, year, edition, pages
London: Informa Healthcare, 2012
Keywords
Fibrinogen, dementia, platelet heterogeneity, platelet in vivo activation, sporadic Alzheimer disease
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-74251 (URN)10.3109/09537104.2011.593654 (DOI)000300047700004 ()
Note
funding agencies|Swedish Board for Health and Welfare||The Ahlens Foundation||Gun and Bertil Stones Foundation||Magn. Bergvalls Foundation||Petrus och Augusta Hedlunds foundation||Pfizer AB||Swedish Alzheimer Foundation||Stiftelsen for Gamla Tjanarinnor||Available from: 2012-01-22 Created: 2012-01-22 Last updated: 2017-12-08
Järemo, P., Milovanovic, M., Nilsson, S., Buller, C., Post, C. & Winblad, B. (2011). Alzheimer's disease is characterized by more low-density erythrocytes with increased volume and enhanced β-amyloid x-40 content [Letter to the editor]. Journal of Internal Medicine, 270(5), 489-492
Open this publication in new window or tab >>Alzheimer's disease is characterized by more low-density erythrocytes with increased volume and enhanced β-amyloid x-40 content
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2011 (English)In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 270, no 5, p. 489-492Article in journal, Letter (Other academic) Published
Place, publisher, year, edition, pages
Wiley-Blackwell, 2011
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-74252 (URN)10.1111/j.1365-2796.2011.02388.x (DOI)000297021600013 ()
Available from: 2012-01-22 Created: 2012-01-22 Last updated: 2017-12-08Bibliographically approved
Milovanovic, M., Fransson, E., Hallert, C. & Järemo, P. (2010). Letter: Atrial fibrillation and platelet reactivity: in International Journal of Cardiology(ISSN 0167-5273)(EISSN 1874-1754) [Letter to the editor]. International Journal of Cardiology, 145(2), 357-358
Open this publication in new window or tab >>Letter: Atrial fibrillation and platelet reactivity: in International Journal of Cardiology(ISSN 0167-5273)(EISSN 1874-1754)
2010 (English)In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 145, no 2, p. 357-358Article in journal, Letter (Other academic) Published
Abstract [en]

BACKGROUND: The impact of atrial fibrillation (AF) upon platelet reactivity has not been investigated.

METHODS: Subjects were 33 individuals with AF who consented to elective electrical cardioversion (ECV) immediately before ECV determination of surface-bound fibrinogen after stimulation i.e. platelet reactivity was carried out. A flow cytometer was employed. ADP (1.7 and 8.5mumol/L) and a thrombin receptor activating peptide (54 and 74mumol/L) were used as agonists. The analyses were repeated after 26+/-8(SD) months.

RESULTS: Compared to day 1 subjects with AF (n=18) had a trend towards lower platelet reactivity at study end. It reached significance when using 1.7mumol/L ADP. In contrast, after 26+/-8(SD) months sinus rhythm (SR) (n=15) was associated with significant lower reactivity with all agonists.

CONCLUSION: After 26+/-8(SD) months patients returning with AF had higher platelet reactivity than those who remained with SR.

Place, publisher, year, edition, pages
Ireland: Elsevier, 2010
Keywords
Atrial fibrillation, Flow cytometry, platelet reactivity, platelet activity
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:liu:diva-59612 (URN)10.1016/j.ijcard.2010.02.030 (DOI)
Note
Original Publication: Micha Milovanovic, Elisabeth Fransson, Claes Hallert and Petter Järemo, Letter: Atrial fibrillation and platelet reactivity, International Journal of Cardiology, 2010. http://dx.doi.org/10.1016/j.ijcard.2010.02.030 Copyright: ElsevierAvailable from: 2010-09-29 Created: 2010-09-21 Last updated: 2017-12-12Bibliographically approved
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