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Acute exacerbations (AE) are severe complications of chronic obstructive pulmonary disease (COPD); however, the need for biomarkers which predict them is still unmet. High platelet count (PLC) and platelet-to-lymphocyte ratio (PLR) are associated with higher mortality in patients with COPD. We investigated if PLC and PLR at the onset of a severe AE could predict the time of the next relapse. In a prospective observational cohort study, data of 152 patients hospitalized with AECOPD were collected, and patients were divided into PLC-low (<239 ​× ​109/L, n ​= ​51), PLC-medium (239-297 ​× ​109/L, n ​= ​51) and PLC-high (>297 ​× ​109/L, n ​= ​50) or PLR-low (<147, N ​= ​51), PLR-medium (147–295, n ​= ​51) and PLR high (>295, n ​= ​50) groups based on PLC and PLR tertiles using admission laboratory results. Clinical characteristics and the time to the next severe or moderate AE within 52 weeks were compared among subgroups using log-rank test. PLC and PLR tertiles did not differ in clinical characteristics or the time till the next AE (p ​> ​0.05). PLC and PLR showed a direct weak correlation to neutrophil count (Pearson r ​= ​0.26, p ​< ​0.01 and r ​= ​0.20, p ​= ​0.01) and PLC also demonstrated a weak relationship to white blood cell counts (Pearson r ​= ​0.29, p ​< ​0.001). However, PLR presented an inverse relationship to monocyte and eosinophil counts (r ​= ​−0.32, p ​< ​0.001 and r ​= ​−0.17, p ​= ​0.03). PLC and PLR do not predict the time till the next relapse; however, they may reflect on neutrophilic inflammatory response during an exacerbation of COPD. [ABSTRACT FROM AUTHOR]

Surgical-induced hemostasis is a critical step in the closure of incisions, which is frequently achieved via electrocauterization and subsequent tissue necrotization. The latter is associated with postoperative complications. Recent in vivo work suggested reactive species-producing gas plasma technology as a pro-homeostatic agent acting via platelet activation. However, it remained elusive how platelet activation is linked to lipid and protein oxidation and the reactive species compositions. A direct relation between the reactive species composition and platelet activation was revealed by assessing the production of several reactive species and by using antioxidants. In addition, platelet lipidome and proteome analysis identified significantly regulated key lipids in the platelet activation pathway, such as diacylglycerols and phosphatidylinositol as well as oxylipins like thromboxanes. Lipid oxidation products mainly derived from phosphatidylethanolamine and phosphatidylserine species were observed at modest levels. In addition, oxidative post-translational modifications were identified on key proteins of the hemostasis machinery. This study provides new insights into oxidation-induced platelet activation in general and suggests a potential role of those processes in gas plasma-mediated hemostasis in particular. [Display omitted] • Direct relation of gas plasma-derived reactive species and human platelet activation found. • Lipidomics and proteomics revealed key lipids and proteins regulated in gas plasma-activated platelets. • Lipid oxidation products and oxidative post-translational modifications identified via high-resolution mass spectrometry. [ABSTRACT FROM AUTHOR]

Platelets are enucleated fragments of cells with a diversity of internal granules. They are responsible for functions related to hemostasis, coagulation, and inflammation. The activation of these processes depends on a cascade coordinated by cytokines, chemokines, and components of purinergic signaling, such as ATP, ADP, and adenosine. Platelets express distinct components of the purinergic system: P2X1, P2Y1, PY12, and P2Y14 receptors; and the ectonucleotidases NTPDase, NPP, and 5NTE (ecto-5′-nucleotidase). Except for P2Y14, which has not yet exhibited a known function, all other components relate to the biological processes mentioned before. Platelets are known to display specific responses to microorganisms, being capable of recognizing pathogen-associated molecular patterns (PAMPs), engulfing certain classes of viruses, and participating in NETosis. Platelet function dysregulation implicates various pathophysiological processes, including cardiovascular diseases (CVDs) and infections. In COVID-19 patients, platelets exhibit altered purinergic signaling and increased activation, contributing to inflammation. Excessive platelet activation can lead to complications from thrombosis, which can affect the circulation of vital organs. Therefore, controlling the activation is necessary to end the inflammatory process and restore homeostasis. Ectonucleotidases, capable of hydrolyzing ATP, ADP, and AMP, are of fundamental importance in activating platelets, promising pharmacological targets for clinical use as cardiovascular protective drugs. In this review, we revisit platelet biology, the purinergic receptors and ectonucleotidases on their surface, and their importance in platelet activity. Additionally, we describe methods for isolating platelets in humans and murine, as well as the main techniques for detecting the activity of ectonucleotidases in platelets. Considering the multitude of functions revealed by platelets and their potential use as potent bioreactors able to secrete and present molecules involved in the communication of the vasculature with the immune system, it is crucial to deeply understand platelet biology and purinergic signaling participation to contribute to the developing of therapeutic strategies in diseases of the cardiovascular, inflammatory, and immune systems. [ABSTRACT FROM AUTHOR]

• Platelet indices were evaluated in dogs with chronic enteropathies (CE) as predictors of disease and severity. • Platelet component distribution width was significantly different in dogs with CE compared to healthy dogs. • Platelet count and platelet dry mass distribution width were significantly associated with higher disease severity scores. Human studies have shown an association between certain platelet indices and active inflammatory bowel disease when compared to healthy controls. The objectives of this retrospective study were to determine if any platelet indices differ between dogs with chronic enteropathies and healthy age- and sex-matched control dogs and are predictive of the severity of chronic enteropathy based on canine chronic enteropathy clinical activity index (CCECAI) scores. Medical records for 22 chronic enteropathy-positive dogs and 22 healthy control dogs were reviewed for historical and physical examination findings, platelet indices, and histologic diagnoses of chronic enteropathy. Platelet indices were compared between the groups, and an association between platelet indices and CCECAI scores in dogs with chronic enteropathy was investigated. Chronic diarrhea and weight loss were common clinical signs associated with chronic enteropathy. Lymphoplasmacytic enteritis was the most common histologic diagnosis. Only one platelet index, platelet component distribution width (P = 0.045), was found to be significantly different between the groups. For predicting severity of disease, determined by CCECAI score, statistically significant differences in indices associated with higher scores were platelet count (P = 0.024) and platelet dry mass distribution width (P = 0.036). Only platelet component distribution width showed potential in characterizing dogs with chronic enteropathy compared to normal dogs. Elevated platelet count and decreased platelet dry mass distribution width had a significant effect on total CCECAI scores. These findings suggest further investigation into the utility of platelet indices as predictors of disease presence and severity in dogs with chronic enteropathy is warranted. [ABSTRACT FROM AUTHOR]

Abstract Fungal hyphae constitute a special challenge for the immune system, since they are too large to be phagocytosed. This review summarizes our current knowledge on those immune cells that are able to attack and eliminate hyphae and we discuss the different means that are employed by these cells in order to kill hyphae. [ABSTRACT FROM AUTHOR]

Recently, ketamine has been investigated as a potential antidepressant option for treatment resistant depression. Unlike traditional drugs, it yields immediate effects, most likely via increased glutamatergic transmission and synaptic plasticity. However, ketamine administration in humans is systemic and its long–term impact on blood parameters has not yet been described in clinical studies. Here we investigated potential sustained effects of ketamine administration (0.5 mg/kg ketamine racemate) on hematological and biochemical values in plasma and serum in a randomized double–blinded study. 80 healthy young participants were included and whole blood samples were collected 5 days before, and 14 days after the infusion. To assess the group effect, repeated measure analyses of co–variance (rmANCOVA) were conducted for the following blood parameters: levels of sodium, potassium, calcium, hemoglobin and number of erythrocytes, lymphocytes , and thrombocytes. RmANCOVA revealed a significant time by treatment effect on thrombocyte levels ( F 1, 74 = 13.54, p < 0.001, eta = 0.155), driven by an increase in the ketamine group (paired t -test, t = −3.51, df = 38, p = 0.001). Specificity of thrombocyte effect was confirmed by logistic regression, and in addition, no other coagulation parameters showed significant interaction. Moreover, the relative increase in the ketamine group was stable across sexes and not predicted by age, BMI, smoking, alcohol or drug use, and contraception. Our results describe aftereffects of sub–anesthetic ketamine administration on blood coagulation parameters, which should be considered especially when targeting psychiatric populations with relevant clinical comorbidities. [ABSTRACT FROM AUTHOR]

The exceptionally high cellular uptake of gold nanorods (GNRs) bearing cationic surfactants makes them a promising tool for biomedical applications. Given the known specific toxic and stress effects of some preparations of cationic nanoparticles, the purpose of this study was to evaluate, in an in vitro and in vivo in mouse, the potential harmful effects of GNRs coated with (16-mercaptohexadecyl)trimethylammonium bromide ( MTAB GNRs). Interestingly, even after cellular accumulation of high amounts of MTAB GNRs sufficient for induction of photothermal effect, no genotoxicity (even after longer-term accumulation), induction of autophagy, destabilization of lysosomes (dominant organelles of their cellular destination), alterations of actin cytoskeleton, or in cell migration could be detected in vitro . In vivo , after intravenous administration, the majority of GNRs accumulated in mouse spleen followed by lungs and liver. Microscopic examination of the blood and spleen showed that GNRs interacted with white blood cells (mononuclear and polymorphonuclear leukocytes) and thrombocytes, and were delivered to the spleen red pulp mainly as GNR-thrombocyte complexes. Importantly, no acute toxic effects of MTAB GNRs administered as 10 or 50 μg of gold per mice, as well as no pathological changes after their high accumulation in the spleen were observed, indicating good tolerance of MTAB GNRs by living systems. [ABSTRACT FROM AUTHOR]

The process of myeloid cell development (myelopoiesis) in fish has mainly been studied in three cyprinid species: zebrafish ( Danio rerio ), ginbuna carp ( Carassius auratus langsdorfii ) and goldfish ( C. auratus , L.). Our studies on goldfish myelopoiesis have utilized in vitro generated primary kidney macrophage (PKM) cultures and isolated primary kidney neutrophils (PKNs) cultured overnight to study the process of macrophage (monopoiesis) and neutrophil (granulopoiesis) development and the key growth factors, receptors, and transcription factors that govern this process in vitro . The PKM culture system is unique in that all three subpopulations of macrophage development, namely progenitor cells, monocytes, and mature macrophages, are simultaneously present in culture unlike mammalian systems, allowing for the elucidation of the complex mixture of cytokines that regulate progressive and selective macrophage development from progenitor cells to fully functional mature macrophages in vitro . Furthermore, we have been able to extend our investigations to include the development of erythrocytes (erythropoiesis) and thrombocytes (thrombopoiesis) through studies focusing on the progenitor cell population isolated from the goldfish kidney. Herein, we review the in vitro goldfish model systems focusing on the characteristics of cell sub-populations, growth factors and their receptors, and transcription factors that regulate goldfish myelopoiesis. [ABSTRACT FROM AUTHOR]

Raising ostriches became an important economic activity after their products became commodities. The health of farm animals is of paramount importance, so assessing basic immunological responses is necessary to better understand health problems. We developed a method to obtain ostrich thrombocytes and macrophages. The thrombocytes died by apoptosis after 48 h in culture, and the macrophages expanded in size and increased the number of acidic compartments. Macrophages were activated by chicken interferon-γ, producing high levels of nitric oxide. Toxoplasma gondii was able to infect these macrophages, and activation controlled parasitic reproduction. T. gondii, however, persisted in these cells, and infection reduced the production of nitric oxide. These results are important for the future assessment of the basic cellular and immunobiology of ostriches and demonstrate T. gondii suppression of nitric oxide production. [ABSTRACT FROM AUTHOR]

Invasive aspergillosis is characterized by vascular invasion and thrombosis. In order to determine the antifungal activity of human platelets, hyphal elongation and metabolic activity of a clinical A. fumigatus isolate were measured. Genome-wide identification of differentially expressed genes in A. fumigatus was performed after exposure to platelets for 15, 30, 60 and 180 min. Data were analyzed by gene ontology annotation as well as functional categories (FunCat) and KEGG enrichment analyses. Platelets attenuated hyphal elongation and viability of A. fumigatus and in total 584 differentially expressed genes were identified, many of which were associated with regulation of biological processes, stress response, transport and metabolism. FunCat and KEGG enrichment analyses showed stress response and metabolic adaptation to be increased in response to platelets. Our findings demonstrate that A. fumigatus displayed a specific transcriptional response when exposed to platelets, thus reflecting their antifungal activities. [ABSTRACT FROM AUTHOR]

There are a lot of natural resources that potentially used as herbal medicines in Indonesia. Some of the herbs, like Dewa leaves ( Gynura pseudochina (L) D.C) and temu ireng rhizome ( Curcuma aeruginosa Roxb.), were ussually used to increase number of thrombocytes in dengue patient. This current study was to determine the potential of dewa leaves ( Gynura pseudochina (L) D.C) and temu ireng rhizome ( Curcuma aeruginosa Roxb.) against the number of trombocytes, erythrocytes, and hematocrits level on male white rats ( Rattus novergicus ) by using Heparin Induction. Dosages of the extracts were 250 mg/kg BW and 500 mg/kg BW used for both dewa leaves and temu ireng rhizome. Extracts were given orally to the tested animals for seven continuous days. The number of trombocytes, erythrocytes, and hematocrites level were examine at day 7 using sysmex XE-5000 hematology analyzer. The result showed that the rat groups which were treated with dewa leaves extract at 500 mg/kgBW; temu ireng Rhizomes extract at 250 mg/kgBW and 500 mg/kgBW dosages had significant differences (α = 0.05) on number of thrombocytes. The percentages of thrombocytes number enhancement for temu ireng rhizomes extract 500 mg/kgBW, temu ireng rhizomes extract 250 mg/kgBW, dewa leaves extract 500 mg/kgBW were 26.98%, 24.48%, 19.44% respectively. The rats group which were treated with temu ireng Rhizomes extract at 500 mg/kgBW, dewa leaves extract at 250 mg/kgBW and 500 mg/kgBW had significant differences (α = 0.05) on erythrocytes number and hematocrits level enhancement. The percentages of erythrocytes number enhancement for dewa leaves extract at dose of 500 mg/kgBW and 250 mg/kgBW, temu ireng rhizomes extract 500 mg/kgBW were 9.59%, 9.11%, 9.02% respectively. The highest percentages of hematocrits level enhancement was given by dewa leaves extract at dose of 500 mg/kgBW (10,97%), suggesting that the extracts treatment would not trigger plasma leakage. Thus, dewa leaves extract at 500 mg/kgBW; temu ireng rhizomes extract at 250 mg/kgBW and 500 mg/kgBW dosages are potential as candidates to be medicinal herbs to increase numbers of thrombocytes on dengue fever treatment [ABSTRACT FROM AUTHOR]

Highlights: [•] We measured blood sphingolipid content in patients with myocardial infarction. [•] Plasma sphingosine-1-phosphate (S1P) concentration was decreased. [•] S1P accumulated in erythrocytes and platelets. [•] S1P release from erythrocytes was not affected. [•] Cardioprotective action of S1P may be diminished in myocardial infarction patients. [ABSTRACT FROM AUTHOR]

Thrombocytopenia is common in trauma and critically ill patients and is associated with a poor outcomes. The objective of this retrospective study was to investigate the course of thrombocyte concentration changes in burn patients, the influences of various factors on this course, and a possible predictive value of thrombocyte counts on outcome in 244 patients admitted to our burn centre. Their thrombocyte counts were obtained until 50 days after burn. Data on patient demographics, total percentage burned surface area (%TBSA), sepsis and mortality were collected. Multilevel multivariable analysis was performed to investigate the influence of the variables on the platelet course. Cox regression analysis was performed to analyse the predictive value of the variables for mortality. A distinct pattern of thrombocyte counts was observed, with a nadir at day 3 followed by a peak at day 15 and a temporary thrombocytosis. %TBSA and age (p <0.05) influence this course. The mean thrombocyte course of septic and non-surviving patients depicts a significant lower nadir. Furthermore, higher age, %TBSA and low thrombocyte counts at the peak are predictive for 50 day mortality (p <0.05). Platelets follow a distinct course after burn, influenced by %TBSA and age. These factors and a low thrombocyte peak count predict mortality. [Copyright &y& Elsevier]

A novel haematology analyser was evaluated for its use with feline samples. Complete blood cell counts, a five-part differential count, and reticulocyte numbers were determined, and the results compared with reference data. Coefficients of correlation, Passing-Bablok regression analysis and Bland-Altmann difference plots with biases and 95g limits of agreement are reported. Precision and linearity were also studied. The instrument demonstrated very low imprecision, and the tested range of linearity exceeded the reference ranges provided by the manufacturer. For all parameters except monocytes (r = 0.65), the analyser results correlated well with reference methods. Compared with the manual count of aggregated reticulocytes, the instrument showed good agreement with a positive bias. The optical platelet count correlated well with the manual chamber count. In conclusion the analyser was found to be highly reliable for the analysis of feline blood samples in a large veterinary laboratory. [ABSTRACT FROM AUTHOR]

Abstract: Blood cells from three different sea turtle species were cultured for approximately 3 weeks in nutrient medium supplemented with recombinant human cytokines known to induce terminal maturation of human hematological stem cells. Cultured turtle erythrocytes were translucent, approximately 10× larger than human erythrocytes, contained a single fluorescent inclusion body, contained nuclear epsilon (embryonic) globin proteins, and, absent of organelles while fresh cells contained few, but well defined mitochondria. Cells with basophilic cytoplasm and in all stages of proliferation were observed in cytokine-supplemented cultures and appeared to possess active protein synthesis. Cultured thrombocytes aggregated in response to agonists for at least 8 days, post-collection, contained P-selectin in the nucleus of 6 day cultured cells which appeared to be released after activation with collagen, and after 6 days had no organelles or open canalicular-like system (OCS) while freshly isolated cells demonstrated few, if any organelles but had a well developed OCS. The response of turtle cells to apparently homologous but unnatural human cytokines and the sustained biological properties of thrombocytes identify this suspension culture system as a powerful tool to explore the evolution of cell types and molecular components of hematopoiesis and hemostasis. [Copyright &y& Elsevier]

Abstract: Plasmodium juxtanucleare is one of the agents that cause chicken malaria. High parasitemia causes anemia, diarrhea and weight loss that leads to death. This parasite is spread through the tropics and little is known about the physiological changes caused by P. juxtanucleare infections in chickens. The aim of this work was to determine hematological changes in chickens experimentally infected with this parasite. No weight or temperature differences between infected and control groups were detected. Low parasitemia was observed reaching a peak after 15 days; trophozoits was the most observed form, followed by schizonts detected on day 12 and gametocytes on day 27. Infected thrombocytes and thrombocytes with pyknotic nuclei and retracted cytoplasm were observed along the experimental infection. No changes were observed on the erythrocyte values. However, a reduction of thrombocyte number and an increase of total leukocyte and basophil numbers, all significant, were detected in infected chickens. Parasitemia was probably kept low by general immunological activation. These results suggest that classical hematology can monitor physiological changes caused by P. juxtanucleare infections in chickens. [Copyright &y& Elsevier]

Summary: The growth factor erythropoietin (EPO) and erythropoietin receptors (EPOR) are expressed in the nervous system. Neuronal expression of EPO and EPOR peaks during brain development and is upregulated in the adult brain after injury. Peripherally administered EPO, and at least some of its variants, cross the blood-brain barrier, stimulate neurogenesis, neuronal differentiation, and activate brain neurotrophic, anti-apoptotic, anti-oxidant and anti-inflammatory signaling. These mechanisms underlie their tissue protective effects in nervous system disorders. As the tissue protective functions of EPO can be separated from its stimulatory action on hematopoiesis, novel EPO derivatives and mimetics, such as asialo-EPO and carbamoylated EPO have been developed. While the therapeutic potential of the novel EPO derivatives continues to be characterized in preclinical studies, the experimental findings in support for the use of recombinant human (rh)EPO in human brain disease have already been translated to clinical studies in acute ischemic stroke, chronic schizophrenia, and chronic progressive multiple sclerosis. In this review article, we assess the studies on EPO and, in particular, on its structural or functional variants in experimental models of nervous system disorders, and we provide a short overview of the completed and ongoing clinical studies testing EPO as neuroprotective/neuroregenerative treatment option in neuropsychiatric disease. [Copyright &y& Elsevier]

Abstract: The leading cause of death in the United States and European countries is coronary heart disease. We hypothesized that the ingestion of soy compounds may not only have beneficial effects on atherosclerotic risk by lowering lipid compounds, but also by reducing platelet aggregability. Therefore, we analyzed in vitro the influence of defined and digestible peptides, frequently found in glycinin and β-conglycinin as important proteins of soy bean, on platelet aggregation of 180 healthy volunteers with or without the isoflavone genistein by aggregometry and flow cytometry. (i) The predominating share of amino acids and acidic, neutral, and basic di- and tripeptides of up to 2 mmol/L did not modify platelet aggregation induced by collagen, adenosine diphosphate, epinephrine, or arachidonic acid. (ii) Genistein inhibited agonist-induced platelet aggregation dose dependently. (iii) In the presence of the acidic peptides glutamate-glutamate and aspartate-aspartate-aspartate (1 mmol/L each), genistein reduced collagen- and ADP-dependent platelet activation stronger than 250 μmol/L of this isoflavone alone. Other peptides were less effective (eg, glutamate-glutamate-glutamate) or ineffective (eg, asparagine-asparagine). (iv) Glutamate-glutamate-glutamate (1 nmol/L), glutamate-glutamate (1 μmol/L), and aspartate-aspartate-aspartate (1 μmol/L) enhanced the inhibition of genistein on platelet aggregation induced by arachidonic acid. Thus, the results of the present in vitro investigation allow the assumption that nutrition with specific compounds of soy—acidic peptides together with genistein—might protect against coronary atherosclerosis by attenuating platelet activity. In vivo studies are warranted to check this assumption. [Copyright &y& Elsevier]

Abstract: Aims: To determine the value of fibrinogen-positive platelet-analysis in predicting restenosis after stent implantation in acute myocardial infarction patients. Methods and results: Our patient population comprised 50 patients who underwent intravascular ultrasound (IVUS) guided stent implantation for acute myocardial infarction. In all cases, IVUS confirmed a deep vessel wall injury due to a ruptured plaque within the culprit lesion. Flow cytometry quantified the amount of platelets with surface-bound fibrinogen and thrombospondin before and immediately after the intervention. After 5 months, IVUS was repeated to assess the long-term results. In-stent restenosis – defined as a percent diameter stenosis of >50% – was detected in 11 of 45 patients who attended follow-up angiography. The amount of fibrinogen-positive platelets was significantly higher among patients who subsequently developed in-stent restenosis (50.5±6.8% fibrinogen-positive platelets immediately after intervention) than among those who did not (39.7±12.3% fibrinogen-positive platelets, p <0.005). Receiver operating characteristic curve revealed a 40% cut-off for fibrinogen-positive platelets immediately after the intervention to predict restenosis (p <0.05, sensitivity: 90.9%, specificity: 47.1%). Conclusion: The amount of fibrinogen-positive platelets immediately after stent implantation predicts the occurrence of in-stent restenosis, as confirmed by IVUS in acute myocardial infarction patients. [Copyright &y& Elsevier]

Abstract: Chicken thrombocytes are equivalent in hemostatic function to mammalian platelets. Platelets are enucleated components of mammalian blood, while thrombocytes are nucleated blood leukocytes of chickens. Platelets and thrombocytes share characteristics that contribute to innate immunity. Experiments were conducted to determine if thrombocytes could respond in vitro to lipopolysaccharide (LPS) of Salmonella minnesota through Toll-like receptor-4 (TLR4). The aim was to activate the signal pathways leading to expression of interleukin-6 (IL-6) and inducible cyclooxygenase (COX-2) and to production of prostaglandin E2 (PGE2). Chicken thrombocytes were found to express TLR4, and LPS-induced an increase in thrombocyte mRNA expression of IL-6 and COX-2 with release of PGE2 into culture media. An increase of COX-2 and PGE2 due to LPS stimulation was inhibited by MEK1 inhibitor PD98059, but IL-6 expression was unaffected by PD98059. The IKK-2 inhibitor BMS345541 inhibited IL-6 and COX-2 with reduction of PGE2 concentrations. Therefore, the MAP kinase (MAPK) pathway activates expression of COX-2 and ultimately PGE2 production, but this pathway has little or no influence on IL-6 expression in thrombocytes. The NF-κB pathway also influences COX-2 expression and PGE2 production, and it is a primary activation signaling cascade for IL-6 gene expression in chicken thrombocytes. Thrombocytes represent a major component of the innate immune system of chickens in response to LPS and possibly other microbial products. [Copyright &y& Elsevier]

Abstract: The hemostatic system in its multiple components displays an intricate organization in time which is characterized by circadian (∼24-hour), circaseptan (∼7-day), menstrual (∼monthly), and circannual (∼yearly) bioperiodicities. The interaction of the rhythms of the variables participating in hemostasis determine transient risk states of thromboembolic events, including myocardial infarction and stroke, and of hemorrhage and hemorrhagic events, each with a unique timing. The circadian staging of the rhythms in vascular, cellular, and coagulation factors that favors blood coagulation and thrombosis coincides with the daily minimum in fibrinolytic activity; as a result there is elevated risk in the morning of acute myocardial infarction and stroke. Similar hemostatic rhythms may determine the epidemiology of thromboembolic and hemorrhagic events during the week, month and year. This article focuses on the large-amplitude circadian rhythms operative in the hemostatic system. Their implication for preventive and curative pharmacotherapy of hemostatic disorders is presented, with discussion of related problems. [Copyright &y& Elsevier]

Abstract: Evaluation of peripheral blood mononuclear cells (PBMC) in avian species by flow cytometry is complicated by the presence of large numbers of nucleated thrombocytes. With light scattering properties similar to those of lymphocytes, variations in the proportion of thrombocytes in PBMC can result in apparent shifts in percentages of lymphocyte subpopulations. We have applied a dual-labeling procedure for flow cytometric analyses to exclude thrombocytes from the analyzed population by labeling with K55 monoclonal antibody (MAb), which differentially labeled leukocyte and thrombocyte populations. Flow cytometric analyses with K55 labeled chicken PBMC differentiated leukocytes into three populations according to their intensity of fluorescence. Using the Kl MAb, the K55-low population was shown to consist of thrombocytes. Dual-labeling with K55 MAb and MAb specific for B lymphocyte, CD4 or CD8 markers indicated that the K55 intermediate population consisted of lymphocytes. Therefore, concentrations of CD4+ and CD8+ T lymphocytes could be determined from the lymphocyte fraction by gating specifically on the K55 intermediate cells. Selecting cross-reactive chicken MAbs that included K55, this protocol was shown to identify CD4+ and CD8+ T lymphocytes in PBMC of another avian species, the endangered Attwater''s prairie chicken. [Copyright &y& Elsevier]

Abstract: Magnesium (Mg) is the second most abundant intracellular cation with modulating properties in a number of metabolic processes, e.g. in glycolysis, and intracellular signalling processes, e.g. regulation of ion channels and transporters. There are conflicting data available about the regulation of Mg in blood cells during exercise. Moreover, there are no data available about changes of the metabolic important fraction of ionized Mg2+ both in blood and in blood cells during exercise. The present study investigated the changes of ionized Mg2+ and total Mg concentration in different compartments after a stepwise treadmill ergometer test. Intracellular ionized Mg2+ of thrombocytes and erythrocytes was determined by the magnesium sensitive fluorescent dyes mag-fura-2 and Mag-Green using fluorescence spectroscopy and flow cytometry, respectively. Ionized Mg2+ in blood/serum was measured by an ion-sensitive microelectrode. Total cellular and serum Mg concentration were investigated using atomic absorbance spectroscopy and photometry, respectively. The present results shown that at the end of the ergometer test, ionized Mg2+ in both blood and serum and total serum Mg decreased. In contrast, intracellular concentration of ionized Mg increased in both thrombocytes and erythrocytes. Total intracellular Mg was unchanged making a Mg2+ shift between the intra- and extracellular compartment unlikely. The present study therefore demonstrated opposite changes of the ratio [ionized Mg2+]/[total Mg] in the intracellular and the extracellular compartment after anaerobic exercise. In in vitro experiments, similar changes of ionized Mg2+ in both compartments could be mimicked by application of weak acids like propionic and lactic acid. It is concluded changes in the fraction of ionized Mg2+ should be high enough to influence intracellular signalling and metabolic processes. [Copyright &y& Elsevier]

The fine structure of the different stages of the Fallisia effusa (Haemosporina: Garniidae), infecting the thrombocytes of the semi-aquatic Amazonian lizard Neusticurus bicarinatus (Reptilia: Teiidae) is described. Gametocytes, meronts, and merozoites of Fallisia effusa were found within a parasitophorous vacuole (PV). Multiple infections of micro- and macrogametocytes were observed. A circumferential coil of microtubules was seen in the cytoplasm of the infected host cell and this microtubule array was pronounced in cells harboring gametocytes. A deep invagination of the inner membrane complex of gametocytes may be involved in nutrition. The non-pigmented parasites underwent both merogony and gametogony in thrombocytes of the peripheral blood. No infection of the erythrocytes was observed. These observations confirm that Fallisia effusa displays characteristic features distinguishing it from other members of the Haemosporidian families, and that it has the ability to modulate microtubule assembly. [Copyright &y& Elsevier]

PURPOSE: To describe the cross-sectional association of counts of total and subtypes of leukocytes, platelets, and selected characteristics of red blood cells with intensity of cigarette smoking and smoking cessation.METHODS: The study population consisted of 16,254 men and women 20–70 years of age who participated in the Dutch European Prospective Investigation into Cancer and nutrition (EPIC) subcohort, 1995–1997. Linear regression analysis was performed, for both sexes separately, to study the relation between various measurements of smoking habits and hematologic characteristics.RESULTS: Among current smokers, in both genders, packyears and daily number of cigarettes were associated with increased leukocytes (6–19%), lymphocytes (4–14%), monocytes (3–9%), neutrophils (7–24%), platelets (1–5%), mean corpuscular volume (0.4–2%), hematocrit (0.3–4%), hemoglobin (0.3–4%), and mean corpuscular hemoglobin (0.8–2%). In subjects who had quitted smoking within two years before blood measurement, hematological characteristics in most cells were similar as in never smokers, whereas normal counts of lymphocytes and monocytes were observed only 2–5 years after quitting.CONCLUSIONS: Our findings suggest a marked influence of current smoking habits on leukocyte counts and, to a lesser extent, on counts of erythrocytes and platelets. Following smoking cessation, at least five years have to pass before changes in all hematological parameters may return to normal values. [Copyright &y& Elsevier]

[Display omitted] • Clinical data suggest that thrombosis limits efficacy of ICIs (e.g. anti-PD-1). • Coagulation suppresses ICIs via platelets, leukocytes and the complement system. • Molecular mechanisms of CAT envision future therapeutic targets to support ICIs. • ICIs combined with anticoagulant LMWHs may improve clinical outcome. Advances in understanding the molecular mechanisms of tumor progression have achieved impressive progress in the treatment of cancer and so-called immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy. Indeed, antibody-based drugs blocking immune escape of tumor cells by modulation of T cell responses are increasingly utilized for a wide range of tumor entities. Nonetheless, response rates remain limited, and the development of secondary resistance is a common problem. In addition, by increasing the immune response a variety of severe side effects are provoked. Next to autoimmune responses, activation of the complement system and skin toxicity, an increased incidence for thrombotic complications has been observed associated with an increased mortality rate. Based on this, it can be postulated that the interplay of coagulation with inflammation in the tumor microenvironment is relevant for each step in the tumor life cycle. This review focuses on the coagulation as central player fostering mechanisms associated with tumor progression. Thus, a better understanding of the molecular pathways involved in the complex interaction of circulating tumor cells, the plasmatic coagulation and immune cells may help to improve therapeutic concepts reducing mortality and morbidity associated with cancer. [ABSTRACT FROM AUTHOR]

Advances in understanding the molecular mechanisms of tumor progression have achieved impressive progress in the treatment of cancer and so-called immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy. Indeed, antibody-based drugs blocking immune escape of tumor cells by modulation of T cell responses are increasingly utilized for a wide range of tumor entities. Nonetheless, response rates remain limited, and the development of secondary resistance is a common problem. In addition, by increasing the immune response a variety of severe side effects are provoked. Next to autoimmune responses, activation of the complement system and skin toxicity, an increased incidence for thrombotic complications has been observed associated with an increased mortality rate. Based on this, it can be postulated that the interplay of coagulation with inflammation in the tumor microenvironment is relevant for each step in the tumor life cycle. This review focuses on the coagulation as central player fostering mechanisms associated with tumor progression. Thus, a better understanding of the molecular pathways involved in the complex interaction of circulating tumor cells, the plasmatic coagulation and immune cells may help to improve therapeutic concepts reducing mortality and morbidity associated with cancer. [ABSTRACT FROM AUTHOR]

We are presenting Raman spectroscopic analysis of dengue virus infection in the human blood sera. Blood samples from 40 individuals infected with dengue virus and 25 healthy volunteers have been used in this study. Raman spectra of all these samples have been acquired in the spectral range from 600 cm −1 to 1750 cm −1 using 532 nm laser as an excitation source. These Raman spectra have been used to analyze the biochemical changes appeared in the blood caused by dengue virus infection. Two Raman lines at 750 cm −1 and 850 cm −1 found in all spectra of dengue infected sera, indicate the presence of adenosine diphosphate (ADP), which is expected to be excreted due to rupturing of thrombocytes. [ABSTRACT FROM AUTHOR]