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Edvardsson, M., Oweling, M. & Jaremo, P. (2023). Diabetes type 2: relationships between lysosomal exocytosis of circulating normal-sized platelets and in vitro alpha-thrombin-evoked platelet responses. Annals of Medicine, 55(1), 1102-1110
Open this publication in new window or tab >>Diabetes type 2: relationships between lysosomal exocytosis of circulating normal-sized platelets and in vitro alpha-thrombin-evoked platelet responses
2023 (English)In: Annals of Medicine, ISSN 0785-3890, E-ISSN 1365-2060, Vol. 55, no 1, p. 1102-1110Article in journal (Refereed) Published
Abstract [en]

Background/objective: Type 2 diabetes is a major risk factor for atherosclerotic disease. It is well agreed that the reactivity of diabetic platelets is increased but how platelet reactivity regulates is unknown. In our laboratory, density separated platelets have been investigated extensively and high- and low-density platelets circulate in an activated state. The density distribution of circulating platelets is altered in diabetes type 2 as well. We hypothesize that such platelets modify whole blood (WB) in vitro a-thrombin-evoked (10 mu M/mL) activity in type 2 diabetes. Thus, the study aims to identify features of circulating normal-sized density subpopulations affecting whole blood (WB) platelet reactivity in type 2 diabetes. Patients and methods: Patients with type 2 diabetes (n = 16) were enrolled. Their normal-sized platelets were divided into density subfractions (n = 16) using continuous polyvinylpyrrolidone-coated silica (Percoll (TM)) gradients (density span, 1.090-1.040 kg/L) containing prostaglandin E-1. The proportions (%) of such density-separated platelets expressing lysosomal-associated membrane protein 1 (LAMP-1) were analyzed using a flow cytometer. Further, determinations of WB alpha-thrombin-evoked (10 U/mL) surface LAMP-1 (an assessment of lysosomal release), the fibrinogen (a(IIb)beta(3)) receptor activity, annexin V (binds to exposed membrane phosphatidylserine), and mitochondrial transmembrane potentials (an estimate of organelle integrity) were performed. Surface LAMP-1 expressions of individual normal-sized platelet density subpopulations were stratified into equal-sized groups (n = 2) depending on reactivity, as judged from the alpha-thrombin-induced WB activity markers. Results: With some exceptions, the proportion of normal-sized circulating platelets showing spontaneous LAMP-1 was strongly associated with WB alpha-thrombin-evoked (10 U/mL) surface LAMP-1 and a(IIb)beta(3) receptor activity. LAMP-1-expressing normal-sized platelets also displayed inverse associations with WB alpha-thrombin-induced surface annexin V and mitochondrial damage, which are features of procoagulant platelets. Conclusions: From the current descriptive work only involving type 2 diabetes, it is impossible to judge whether the findings are features of the disease or if they occur in healthy individuals as well. However, the study describes LAMP-1 expressing subpopulations of circulating normal-sized platelets that associate with WB a-thrombin (10 U/mL) responses in vitro. Increased proportions of such platelets induced lysosomal release and a(IIb)beta(3) receptor activity, whereas lower proportions promoted WB agonist-induced procoagulant platelet creation. It is to hypothesize that the new described regulatory mechanism could in the future offer a possibility to influence platelet behavior in type 2 diabetes. KEY MESSAGES circle Lysosomal exocytosis of circulating platelets influences reactivity, as determined by agonistinduced platelet reactions in vitro circle Thus, the low release of lysosomes by normal-sized platelets in vivo increases agonist-evoked procoagulant platelet production. circle Higher lysosomal exocytosis of circulating normal-sized platelets promotes platelet aggregation and secretion.

Place, publisher, year, edition, pages
TAYLOR & FRANCIS LTD, 2023
Keywords
Annexin V; alpha(IIb)beta(3) activity; lysosomal-associated membrane protein 1; platelets; platelet reactivity
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:liu:diva-193114 (URN)10.1080/07853890.2023.2171108 (DOI)000955947400001 ()36924419 (PubMedID)
Note

Funding Agencies|OEstergoetland County Council, Sweden

Available from: 2023-04-17 Created: 2023-04-17 Last updated: 2024-05-05
Edvardsson, M., Sund-Levander, M., Milberg, A., Ernerudh, J., Wressle, E., Marcusson, J. & Grodzinsky, E. (2022). Classification of ≥80-year-old individuals into healthy, moderately healthy, and frail based on different frailty scores affects the interpretation of laboratory results. Asian Journal of Medical Sciences, 13(9), 63-71
Open this publication in new window or tab >>Classification of ≥80-year-old individuals into healthy, moderately healthy, and frail based on different frailty scores affects the interpretation of laboratory results
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2022 (English)In: Asian Journal of Medical Sciences, ISSN 2467-9100, E-ISSN 2091-0576, Vol. 13, no 9, p. 63-71Article in journal (Refereed) Published
Abstract [en]

Background: Interpretation laboratory analyses are crucial when assessing the patient’s condition. Reference intervals from apparently healthy and disease-free individuals may cause problems when outcomes from elderly patients with chronic diseases and on medications are being interpreted. Elderly individuals are a heterogeneous group ranging from individuals managing their daily life independently to individuals with diseases and impairment, in need of nursing care around the clock, that is, frail; a term widely used although there is no consensus on the definition.

Aims and Objectives: The aim of the study was to study the effect of classification of elderly into healthy, moderately healthy, and frail, based on activities of daily living (ADL) and Mini-Mental State Examination (MMSE) or frailty index (FI), on the interpretation of outcomes regarding: Albumin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine, and gamma-glutamyltransferase (γ-GT) levels.

Materials and Methods: Individuals ≥80 years (n=568) were classified either on ADL and MMSE or number of deficits, (FI).

Results: Individuals classified as frail based on FI had lower mean levels for ALT, creatinine and γ-GT than individuals classified based on ADL and MMSE (P<0.05).

Conclusion: The model to define health status to some extent affected laboratory analyte levels in ≥80 years old, classified as healthy, moderately healthy, and frail based on ADL and MMSE versus FI.

Place, publisher, year, edition, pages
Nepal Journals Online (NepJOL), 2022
Keywords
Aging; Frail elderly; Analyte; Reference interval; Clinical interpretation
National Category
Geriatrics Clinical Laboratory Medicine
Identifiers
urn:nbn:se:liu:diva-192092 (URN)10.3126/ajms.v13i9.45298 (DOI)
Available from: 2023-03-01 Created: 2023-03-01 Last updated: 2024-04-30
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-3119-4560

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