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Mean Platelet Volume and Peripheral Blood Count Response in Acute Ischemic Stroke
Baburhan Guldiken,Hulya Ozkan,Levent Kabayel
Trakya Universitesi Tip Fakultesi Dergisi , 2008,
Abstract: Objectives: Mean platelet volume (MPV) is a marker of the platelet activity and is reported to increase in vascular diseases. The aim of the study is to investigate the relationship between MPV and the subtypes of acute ischemic stroke.Patients and Methods: The patient group consisted of 102 acute ischemic stroke patients who were divided into the large vessel (n=43) and the small vessel (n=59) disease subgroups. Their MPV values were compared with those of 48 age/sex-matched healthy individuals. The relationship of MPV with the subtypes and severity of stroke, and other hematological parameters (platelet count, platecrit, hemoglobin, hematocrit, erythrocyte count, mean corpuscular volume, leukocyte, neutrophil, lymphocyte, monocyte) was further investigated.Results: No difference was found in terms of MPV values between the patient subgroups and control group, and no relation was found between MPV and stroke severity and other hematological parameters (p>0.05). A significant increase in the leukocyte and neutrophil count was seen in patients of the large vessel disease group when compared with the small vessel disease and control group (p<0.005). Neutrophil count is found to be a risk factor for the stroke severity (β=0.362, p=0.01, OR=1.437, CI %95 0.02-0.08).Conclusion: No significant change in MPV was seen in acute ischemic stroke. High leukocyte and neutrophil levels are markers for the large vessel disease subtype and severity of ischemic stroke.
The Potential of Tetrandrine as a Protective Agent for Ischemic Stroke  [PDF]
Yun Chen,Ya-Hui Tsai,Sheng-Hong Tseng
Molecules , 2011, DOI: 10.3390/molecules16098020
Abstract: Stroke is one of the leading causes of mortality, with a high incidence of severe morbidity in survivors. The treatment to minimize tissue injury after stroke is still unsatisfactory and it is mandatory to develop effective treatment strategies for stroke. The pathophysiology of ischemic stroke is complex and involves many processes including energy failure, loss of ion homeostasis, increased intracellular calcium level, platelet aggregation, production of reactive oxygen species, disruption of blood brain barrier, and inflammation and leukocyte infiltration, etc. Tetrandrine, a bisbenzylisoquinoline alkaloid, has many pharmacologic effects including anti-inflammatory and cytoprotective effects. In addition, tetrandrine has been found to protect the liver, heart, small bowel and brain from ischemia/reperfusion injury. It is a calcium channel blocker, and can inhibit lipid peroxidation, reduce generation of reactive oxygen species, suppress the production of cytokines and inflammatory mediators, inhibit neutrophil recruitment and platelet aggregation, which are all devastating factors during ischemia/reperfusion injury of the brain. Because tetrandrine can counteract these important pathophysiological processes of ischemic stroke, it has the potential to be a protective agent for ischemic stroke.
Peripheral leukocyte counts and outcomes after intracerebral hemorrhage
Shruti Agnihotri, Alexandra Czap, Ilene Staff, Gil Fortunato, Louise D McCullough
Journal of Neuroinflammation , 2011, DOI: 10.1186/1742-2094-8-160
Abstract: Patients with spontaneous ICH admitted to a tertiary care center between January 2005 and April 2010 were included. The change in leukocyte count was measured as the difference between the maximum leukocyte count in the first 72 hours and the leukocyte count on admission. Mortality was the primary outcome. Secondary outcomes were mortality at 1 year, discharge disposition and the modified Barthel index (MBI) at 3 months compared to pre-admission MBI. 423 cases were included. The in-hospital mortality was 30.4%. The change in leukocyte count predicted worse discharge disposition (OR = 1.258, p = 0.009). The change in leukocyte count was also significantly correlated with a decline in the MBI at 3 months. These relationships remained even after removal of all patients with evidence of infection.Greater changes in leukocyte count over the first 72 hours after admission predicted both worse short term and long term functional outcomes after ICH.Cerebrovascular disease is the leading cause of morbidity and mortality in the United States. Intracerebral hemorrhage (ICH) is a devastating subtype of stroke, which has worse outcomes than ischemic stroke, is increasing in prevalence, and has a 30 day mortality of 40-50% [1,2]. Only 20% of patients with ICH return to independent function at 6 months [2,3]. Despite advances in management, the mortality of ICH has not changed significantly over time [4]. The role of inflammation in the pathophysiology of ICH is now increasingly recognized. In animal models, a robust inflammatory response is triggered by the entry of blood into the brain parenchyma [5] with a subsequent infiltration of peripheral leukocytes, activation of microglia and release of cytokines [6,7]. Autopsies in both animals [8] and humans [9] with ICH demonstrate leukocytic infiltration usually within first 3 days and inflammatory changes in the penumbra of the hemorrhage. Few clinical studies have demonstrated association between the inflammatory markers and outcom
Reduced blood brain barrier breakdown in P-selectin deficient mice following transient ischemic stroke: a future therapeutic target for treatment of stroke
Albert Y Jin, Ursula I Tuor, David Rushforth, Jaspreet Kaur, Robert N Muller, Jodie Petterson, Sébastien Boutry, Philip A Barber
BMC Neuroscience , 2010, DOI: 10.1186/1471-2202-11-12
Abstract: MRI confirmed similar infarct sizes and T1 values at 24 hours following stroke for both WT and KO animals. However, the blood to brain transfer constant for Gd DTPA (Kgd) demonstrated greater tissue extravasation of Gd DTPA in WT animals than KO mice (P < 0.03). In the P selectin KO mice, Δ T1 stroke -Δ T1 contralateral control cortex, decreased significantly in the Gd-DTPA(sLeX) group compared to Gd-DTPA, indicative of sLeX mediated accumulation of the targeted contrast agent. Regarding BBB function, in the P-selectin KO mice compared to WT control mice, there was an attenuation in the extravasation of IgG (P < 0.001), a trend for decreased FITC extravasation and less infiltration of PMN leukocytes (P < 0.001) thereby supporting the observed increase in Kgd permeability in stroke brain of WT compared to KO mice.P-selectin expression contributes to enhanced BBB dysfunction at 24 hours after transient focal cerebral ischemia.Leukocyte recruitment occurs after ischemia/reperfusion resulting in local tissue damage and compromised microvascular perfusion. Central to this process is the vascular endothelium expression of P- and E-selectin in the first few minutes to hours after cerebral ischemia, leading to polymorphonuclear (PMN) leukocyte or neutrophil migration into brain tissue, cytokine release and free radical-mediated damage [1]. During this time, blood brain barrier (BBB) injury can lead to an increase in vascular permeability and brain edema, exacerbating the initial ischemic injury [2]. Although neuroinflammatory processes contribute to BBB breakdown in many conditions [3], the link between early BBB dysfunction and endothelial cell activation in acute stroke is unclear. There is evidence that the inhibition of selectin adhesion molecules reduces brain injury and inhibits neutrophil and platelet accumulation after focal ischemia in mice [4,5], but the mechanisms involved in this protection remain speculative [6].We hypothesized that since there is evidence that
Etiologic Overlaps Based on the Brain Infarct Topography  [cached]
K Ghandehari,A Shuaib
Journal of Research in Medical Sciences , 2005,
Abstract: Background: Etiologic overlaps may occur in patients with ischemic stroke depending on the diagnostic investigations and classification criteria. Methods: Consecutive ischemic stroke patients admitted in Mackenzie hospital, Canada from August 2003 to August 2004 underwent a standard battery of diagnostic investigations by stroke neurologists. Stroke mechanism was defined based on the Toast criteria. Stroke topography subtypes were small and large artery territory infarcts. Results: A total of 302 stroke patients (159 female, 143 male) were registered. Small and large artery territory infarcts consisted 25.5% and 74.5% of our topography respectively. Etiologic overlaps were found in 17.5% of the patients. Cardiac source of embolism was significantly more frequent in patients with large artery territory infarcts (p= 0.002) but frequency difference of corresponing large artery atherosclerotic stenosis was not significant in these topographies (p= 0.378). Etiologic overlaps were more frequent in patients with small artery territory infarcts (p= 0.004). Conclusion: Etiologic overlaps are frequent and should be considered for optimal management of the ischemic stroke patients. Key words: Etiology, Mechanism, Overlap, Stroke, Coexistence
Effect of neutrophil depletion on gelatinase expression, edema formation and hemorrhagic transformation after focal ischemic stroke
Alex K Harris, Adviye Ergul, Anna Kozak, Livia S Machado, Maribeth H Johnson, Susan C Fagan
BMC Neuroscience , 2005, DOI: 10.1186/1471-2202-6-49
Abstract: Anti-PMN treatment caused successful depletion of neutrophils in treated animals. There was no difference in either infarct volume or hemorrhage between control and PMN depleted animals. While there were significant increases in gelatinase (MMP-2 and MMP-9) expression and activity and edema formation associated with ischemia, neutrophil depletion failed to cause any change.The main finding of this study is that, in the absence of circulating neutrophils, MMP-2 and MMP-9 expression and activity are still up-regulated following focal cerebral ischemia. Additionally, neutrophil depletion had no influence on indicators of ischemic brain damage including edema, hemorrhage, and infarct size. These findings indicate that, at least acutely, neutrophils are not a significant contributor of gelatinase activity associated with acute neurovascular damage after stroke.The matrix metalloproteinases (MMPs) are a family of some 23 zinc dependent proteases that, collectively, possess the ability to degrade nearly every component of the extra-cellular matrix [1-3]. The activity of the MMPs is tightly controlled through proteolytic activation of the zymogen forms and stoichiometric binding of tissue inhibitors of metalloproteinases (TIMPs). The MMPs play an important role in many physiological processes due to their inherent ability to remodel tissues [2,3]. However, in disease states such as vascular disease and stroke, the MMPs may become deleterious due to dysregulation and can result in tissue injury and inflammation. Specifically, the MMPs may be involved in the degradation of the basal lamina in reperfusion injury resulting in disruption of the blood brain barrier and hemorrhagic transformation [4].Recently, several lines of evidence have demonstrated the involvement of the MMPs in cerebral ischemia. Studies in rat, mouse, and baboon models have shown that MMP-9 is up-regulated following transient focal ischemia [5-8]. Additionally, Asahi et al. have shown that MMP-9 knockout as
Leukocyte Counts, Myeloperoxidase, and Pregnancy-Associated Plasma Protein A as Biomarkers for Cardiovascular Disease: Towards a Multi-Biomarker Approach  [PDF]
M. B. I. Lobbes,M. E. Kooi,E. Lutgens,A. W. Ruiters,V. Lima Passos,S. H. J. G. Braat,M. Rousch,H. Ten Cate,J. M. A. van Engelshoven,M. J. A. P. Daemen,S. Heeneman
International Journal of Vascular Medicine , 2010, DOI: 10.1155/2010/726207
Abstract: We evaluated leukocyte counts and levels of CRP, fibrinogen, MPO, and PAPP-A in patients with stable and unstable angina pectoris, acute myocardial infarction, and healthy controls. All biomarkers were analyzed again after 6 months. Leukocyte counts and concentrations of fibrinogen, CRP, MPO, and PAPP-A were significantly increased in patients with acute myocardial infarction. Leukocyte counts and concentrations of MPO were significantly increased in patients with unstable angina pectoris compared with controls. After 6 months, leukocyte counts and MPO concentrations were still increased in patients with acute myocardial infarction when compared to controls. Discriminant analysis showed that leukocyte counts, MPO, and PAPP-A concentrations classified study group designation for acute coronary events correctly in 83% of the cases. In conclusion, combined assessment of leukocyte counts, MPO, and PAPP-A was able to correctly classify acute coronary events, suggesting that this could be a promising panel for a multibiomarker approach to assess cardiovascular risk. 1. Introduction Atherosclerosis is an inflammatory disease of the large arteries that is characterized by the formation of atherosclerotic plaques. In the majority of cases, atherosclerosis-related clinical events, like myocardial infarction or ischemic stroke, are caused by rupture of a vulnerable atherosclerotic lesion [1–3]. Several inflammatory molecules have been put forward as biomarkers for plaque vulnerability. Biomarkers are biochemical features that can be used to measure the presence of a certain disease, the disease progress, or the effect of treatment [4]. In the context of atherosclerosis, concentrations of C-reactive protein (CRP) and fibrinogen and the count of leukocytes in blood have been investigated most extensively [5–7]. However, large meta-analyses have demonstrated that their prognostic value for assessing risk of cardiovascular disease or adverse outcomes is limited [7–10]. Therefore, there is a continuous search for novel, more powerful biomarkers that are able to predict the occurrence of future cardiovascular complications. Until now, no single biomarker has been able to accurately predict the risk of near-future cardiovascular events in the individual patient. The general opinion is therefore shifting towards a so-called “multi-biomarker” approach, in which a certain panel of biomarkers is assessed to determine an individual risk profile of a patient for cardiovascular disease [4]. However, it remains unclear which biomarkers should be included in this panel. Our study
Association between diabetes complications and leukocyte counts in Iranian patients  [cached]
Moradi S,Kerman SRJ,Rohani F,Salari F
Journal of Inflammation Research , 2012,
Abstract: Sedigheh Moradi1, Scott Reza Jafarian Kerman2, Farzaneh Rohani1, Fereshteh Salari21Endocrine and Metabolism Research Center (Firouzgar), Hemmat Campus, Tehran University of Medical Sciences, Tehran, Iran, 2Scientific Students Research Committee, Tehran University of Medical Sciences, Tehran, IranBackground: The long term complications of diabetes can be fatal. They are also renowned for being an economic burden. Previous studies have demonstrated a relationship between inflammatory markers and complications of diabetes. The objective of this study was to evaluate the relationship between leukocyte counts and these complications.Methods: The study included 184 patients diagnosed with type 2 diabetes. The study was carried out in Iran during 2007 and 2008. Data collected on the subjects were as follows: age, gender, weight, height, blood pressure, smoking history, lipid profile including low density lipoprotein (LDL), high density lipoprotein (HDL), total cholesterol, triglycerides, and leukocyte count, albuminuria, and retinopathy. Furthermore, information on cardiac history for 100 patients was collected. The subjects were split into two groups according to their leukocyte levels: low (≤7000/mm3) and high (>7000/mm3); and then analyzed by Student's t-test or Mann–Whitney U-test as appropriate.Results: The average leukocyte count in these patients was 7594 ± 1965/mm3. Leukocyte count was significantly different in patients with and without retinopathy and albuminuria (P < 0.0001). According to this analysis, a leukocyte count of 6750/mm3 with a sensitivity of 80.2% and a specificity of 56.4%, and a count of 7550/mm3 with a sensitivity of 63.2% and a specificity of 74.6% indicated at least one diabetes complication.Conclusion: An elevated leukocyte count even within the normal range was associated with chronic complications in type 2 diabetes.Keywords: leukocytes, diabetes complications, inflammation
Association between diabetes complications and leukocyte counts in Iranian patients
Moradi S, Kerman SRJ, Rohani F, Salari F
Journal of Inflammation Research , 2012, DOI: http://dx.doi.org/10.2147/JIR.S26917
Abstract: ssociation between diabetes complications and leukocyte counts in Iranian patients Original Research (2113) Total Article Views Authors: Moradi S, Kerman SRJ, Rohani F, Salari F Published Date January 2012 Volume 2012:5 Pages 7 - 11 DOI: http://dx.doi.org/10.2147/JIR.S26917 Received: 06 October 2011 Accepted: 22 November 2011 Published: 24 January 2012 Sedigheh Moradi1, Scott Reza Jafarian Kerman2, Farzaneh Rohani1, Fereshteh Salari2 1Endocrine and Metabolism Research Center (Firouzgar), Hemmat Campus, Tehran University of Medical Sciences, Tehran, Iran, 2Scientific Students Research Committee, Tehran University of Medical Sciences, Tehran, Iran Background: The long term complications of diabetes can be fatal. They are also renowned for being an economic burden. Previous studies have demonstrated a relationship between inflammatory markers and complications of diabetes. The objective of this study was to evaluate the relationship between leukocyte counts and these complications. Methods: The study included 184 patients diagnosed with type 2 diabetes. The study was carried out in Iran during 2007 and 2008. Data collected on the subjects were as follows: age, gender, weight, height, blood pressure, smoking history, lipid profile including low density lipoprotein (LDL), high density lipoprotein (HDL), total cholesterol, triglycerides, and leukocyte count, albuminuria, and retinopathy. Furthermore, information on cardiac history for 100 patients was collected. The subjects were split into two groups according to their leukocyte levels: low (≤7000/mm3) and high (>7000/mm3); and then analyzed by Student's t-test or Mann–Whitney U-test as appropriate. Results: The average leukocyte count in these patients was 7594 ± 1965/mm3. Leukocyte count was significantly different in patients with and without retinopathy and albuminuria (P < 0.0001). According to this analysis, a leukocyte count of 6750/mm3 with a sensitivity of 80.2% and a specificity of 56.4%, and a count of 7550/mm3 with a sensitivity of 63.2% and a specificity of 74.6% indicated at least one diabetes complication. Conclusion: An elevated leukocyte count even within the normal range was associated with chronic complications in type 2 diabetes.
The relation between differential leukocyte count, neutrophil to lymphocyte ratio and the presence and severity of coronary artery disease  [PDF]
Hatice Selcuk, Lale Dinc, Mehmet Timur Selcuk, Orhan Maden, Ahmet Temizhan
Open Journal of Internal Medicine (OJIM) , 2012, DOI: 10.4236/ojim.2012.23025
Abstract: Objectives: Total leukocyte count, a marker of inflammation has long been reported to be related with coronary artery disease (CAD). Recently, differenttial leukocyte count and elevated neutrophil to lymphocyte ratio (N/L) has been shown to indicate an increased long-term risk of mortality in patients with stable CAD, myocardial infarction and undergoing cardiovascular surgery. Thses studies offer incremental prognostic value to total leukocyte count. We sought to determine the relationship between the leukocyte subtypes and N/L ratio and the presence and extent of CAD. Study design: The study consisted of 107 patients [70 (65.4%) men, 37 (34.6%) women, mean age 59.5 ± 10.6 years] referred to coronary angiography with suspected CAD. The subjects were classified into two groups according to the presence of significant CAD and the extent of CAD was determined by the Gensini method. Results: The lymphocyte count was found to be lower (2031 ± 741 cells/μL vs 2392 ± 611 cells/μL, p: 0.010) and the N/L ratio was found to be higher in patients with CAD (2.86 ± 1.57 vs 2.04 ± 1.01, p < 0.001). In correlation analysis, the lymphocyte count and N/L ratio were significantly correlated with the presence and severity of CAD. Multivariate analysis identified N/L as the only independent pre dictor of CAD after adjustment for traditional cardiovascular risk factors [odds ratio: 1.961, 95% confidence interval (1.223, 3.143), p: 0.005]. Conclusion: Our findings reveal that N/L ratio, a simple marker which can be derived from a routine complete blood count test was significantly and independently related to presence and severity of coronary atherosclerosis.
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