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Platelets are valuable, but highly perishable, blood components used in the treatment of, among others, viral dengue fever, blood-related illness, and post-chemotherapy following cancer. Given the short shelf-life of 3–5 days and a highly volatile supply and demand pattern, platelet inventory allocation is a challenging task. This is especially prevalent in emerging economies where demand variability is more pronounced due to neglected tropical diseases, and a perpetual shortage of supply. The consequences of which have given rise to an illegal 'red market'. Motivated by experience at a regional hospital in India, we investigate the problem of platelet allocation among three priority-differentiated demand streams. Specifically we consider a central hospital which, in addition to internal emergency and non-emergency requests, faces external demand from local clinics. We analyze the platelet allocation decision from a social planner's perspective and propose an allocation heuristic based on revenue management (RM) principles. The objective is to maximize total social benefit in a highly supply-constrained environment. Using data from the aforementioned Indian hospital as a case study, we conduct a numerical simulation and sensitivity analysis to evaluate the allocation heuristic. The performance of the RM-based policy is evaluated against the current sequential first come, first serve policy and two fixed proportion-based rationing policies. It is shown that the RM-based policy overall dominates, serves patients with the highest medical urgency better, and can curtail patients' need to procure platelets from commercial sources. [ABSTRACT FROM AUTHOR]

Introduction: Tissue factor (TF) and factor (F) VII, components of the extrinsic pathway of blood coagulation, are essential for hemostatic plug formation in response to injury; less clear are their roles in propagating thrombosis, as observational data in humans with congenital FVII deficiency suggests persistent thrombotic and bleeding risk even at significantly decreased FVII levels. We aimed to define the contribution of FVII to thrombus formation and hemostasis using a non-human primate model. Methods: We treated baboons with a FVII antisense oligonucleotide (ASO) and measured platelet and fibrin deposition inside and distal to collagen- or TF-coated vascular grafts. We assessed hemostasis by measuring bleeding time (BT) and prothrombin time (PT). Enoxaparin and vehicle treatments served as controls. Results: FVII–ASO treatment reduced FVII levels by 95% and significantly increased both the PT and BT. Lowering FVII levels did not decrease platelet deposition in collagen- or TF-coated grafts, in thrombi distal to the grafts, or fibrin content of either collagen- and TF-coated grafts. Lowering FVII levels were associated with a modest 25% reduction in platelet deposition at 60 min in the distal thrombus tail of TF-coated grafts only. Conclusions: FVII inhibition by way of ASO is feasible yet significantly impairs hemostasis while only exhibiting antithrombotic effects when thrombosis is initiated by vessel wall surface-associated TF exposure. [ABSTRACT FROM AUTHOR]

Patchouli oil, an essential aroma oil extracted from patchouli leaf during short-term exposure with five and ten drops either inhibited (at 1 or 2 h) or stimulated (at 4 h) the platelet MAO-A activity depending on the dosages of the aroma oil mainly due to inhibition or stimulation of its Km. The long-term 15 consecutive days exposure (with two or five drops) of patchouli oil, on the other hand, maximally stimulated the platelet MAO-A activity with five drops patchouli oil for 1 h exposure, but further continuation of its exposure with same doses (two or five drops) for 30 consecutive days significantly stimulated (with two drops) and inhibited (with five drops) the platelet MAO-A activity due to stimulation and inhibition respectively of its corresponding both Km and Vmax. These results thus suggest that this aroma oil exposure may modulate the blood platelet serotonergic regulation depending on the dose, duration, and conditions of exposure. [ABSTRACT FROM AUTHOR]

It is well known that the monoamine oxidase (MAO) activity deregulates during aging along with anti-oxidant activity. Carnosine (β-Ala- l-His) is an endogenous dipeptide biomolecule, having both anti-oxidant and anti-glycating properties. The present study deals with the effect of carnosine on aging-induced changes in MAO-A mRNA expression of brain regions and blood platelets in relation to their MAO-A activity. Results showed that aging significantly and characteristically increased the brain regional MAO-A mRNA whereas, in blood platelets it was significantly reduced with an increase in blood platelet counts. Carnosine attenuated both aging-induced (i) increase in brain regional MAO-A mRNA expression and blood platelet count, (ii) decrease in blood platelet MAO-A mRNA expression and its (platelet MAO-A) activity without affecting the young rats' brain regions and platelet. The present results thus suggest that carnosine attenuated and restored the aging-induced (a) increase of platelet count and (b) changes in brain regional and blood platelet MAO-A mRNA expression and (c) decrease in platelet MAO-A activity, towards their respective basal level that were observed in young rats. [ABSTRACT FROM AUTHOR]

Platelet mitochondrial MAO-A activity of male albino rats (Wistar strain) was significantly inhibited with an inhibition of its only V during aging. This age-induced inhibition of platelet MAO-A activity became reversed following the application of higher dosages (2.0-2.5 μg/kg/day, i.t. for 21 consecutive days) of carnosine. Though carnosine at lower dosage (0.5 μg/kg/day, i.t. for 21 consecutive days) was ineffective to platelet mitochondrial MAO-A activity in both young and aged rats, at higher dosages (2.0-2.5 μg/kg/day, i.t. for 21 consecutive days) under similar condition this enzyme activity was significantly enhanced. Carnosine at 1.0 μg/kg/day, i.t. for 21 consecutive days significantly enhanced MAO-A activity only in aged (18 and 24 months) rats. These results suggest that carnosine withdraws the aging-induced inhibition of mammalian blood platelet MAO-A activity and restores its activity towards that (MAO-A activity) observed in young mammalian blood platelets. [ABSTRACT FROM AUTHOR]

Objective: The mechanism action of the polyphenol-rich extracts from berries of Aronia melanocarpa (black chokeberry) and from grape seeds in the defence against homocysteine (Hcy) and its derivatives action in blood platelets is still unknown. In this study, the influence of the aronia extract and grape seeds extract (GSE) on the platelet adhesion to collagen and fibrinogen and the platelet aggregation during a model of hyperhomocysteinemia was investigated. The aim of our study in vitro was also to investigate superoxide anion radicals (O) production after incubation of platelets with Hcy, HTL and the aronia extract and GSE during a model of hyperhomocysteinemia (induced by reduced form of homocysteine at final dose of 100 μM) and the most reactive form of Hcy-its cyclic thioester, homocysteine thiolactone (HTL, 1 μM). Moreover, the additional aim of our study was also to establish and compare the influence of the aronia extract, GSE and resveratrol (3,4′,5-trihydroxystilben), a phenolic compound, which has been supposed to be beneficial for the prevention of cardiovascular events, on selected steps of platelet activation. Methods: The effects of tested extracts on adhesion of blood platelets to collagen and fibrinogen were determined according to Tuszynski and Murphy. The platelet aggregation was determined by turbidimetry method using a Chrono-log Lumi-aggregometer. Results: We have observed that HTL, like its precursor-Hcy stimulated the generation of O (measured by the superoxide dismutase-inhibitable reduction of cytochrome c) in platelets and caused an augmentation of the platelet adhesion and aggregation induced by the strong physiological agonist-thrombin. Our present results in vitro also demonstrated that the aronia extract and grape seeds extract reduced the toxicity action of Hcy and HTL on blood platelet adhesion to collagen and fibrinogen, the platelet aggregation and superoxide anion radicals production in platelets, suggesting its potential protective effects on hemostasis during hyperhomocysteinemia. Conclusion: In the comparative studies, the aronia extract was found to be more effective antiplatelet factors, than GSE or resveratrol during a model of hyperhomocysteinemia. It gives hopes for development of diet supplements, which may be important during hyperhomocysteinemia. [ABSTRACT FROM AUTHOR]

The quantum mechanics computation of the reactivities of chloramine derivatives of amino acids and taurine has been accomplished. A pair of computational indices that reflect a predisposition of alpha amino acid chloramines to chemical decay have been revealed. One of the indices was the dihedral angle for the chain of four atoms: carbons at beta- and alpha-positions, carbon of the carboxyl group, and carbonyl oxygen. The second index was the sum of partial charges for three or two carbon atoms in the chain. The amino acid chloramines with high values of the indices showed enhanced stability. Partial charges for active chlorine in known chloramines having different structures have been computed. The charges correlate with the rate constants of the reaction between chloramines and the thiol group of reduced glutathione. New derivatives of taurine chloramines have been constructed via the introduction of different substituents into the chloramine part. Among them, the amidoderivatives had the greatest charges of active chlorine (0.19-0.23). It was found in the study of the reactions of N-acetyl-N-chlorotaurine and N-propyonyl-N-chlorotaurine with amino acids and peptides possessing the thiol, thioester, or disulphide groups that the amidoderivatives manifested the thiol chemoselectivity. N-acetyl-N-chlorotaurine and N-propionyl-N-chlorotaurine suppress the aggregation activity of blood platelets under their activation by the agonists ADP and collagen. It is not excluded that the amidoderivatives studied prevent platelet aggregation by a modification of the critical thiol group in the purine receptor P2Y12. [ABSTRACT FROM AUTHOR]

Studies were carried out in vitro to determine effects of tranylcypromine enantiomers ([+]- and [−]-TCP) on uptake and release of 5-HT, DA and NA in rat synaptosomes and on imipramine binding to rabbit platelets. (+)-TCP was more potent than (−)-TCP as inhibitor of 5-HT uptake and imipramine binding, whereas (−)-TCP was more potent than (+)-TCP as inhibitor of DA and NA uptake. The enantiomers differed only slightly in their effects on monoamine release. The findings agree with previous reports on the stereoselectivity of monoaminergic mechanisms toward TCP enantiomers, and support the notion that the 5-HT uptake site may be associated with the imipramine binding site. [ABSTRACT FROM AUTHOR]

Nonionic contrast media (NICM) used in radiology exhibit weaker anticoagulant properties than ionic media. This study was intended to evaluate the effect of iopromide NICM upon the platelet aggregation and their membrane structure (investigated by electron paramagnetic resonance method with a spin label). Blood was collected directly from the left ventricle during coronary angiography prior to and following the application of the contrast medium. These results were compared with in vitro examinations. Based on the spectral curves parameters that reflect conformational changes in membrane proteins were determined. The iopromide-induced decrease in platelet aggregation examined in vitro with adenosine diphosphate (ADP), collagen and ristocetine was statistically significant. In vitro platelet membrane structure was modified significantly with regard to both protein conformation and the accessibility of sulfhydryl (- SH) and amino (- NH) groups. In ex vivo studies the changes in platelet aggregation was only observed with ADP, whereas in the membrane-structure modifications were only noted regarding accessibility of - SH and - NH groups. We conclude that iopromide-induced platelet aggregation changes are most probably due to their membrane-structure modifications, whereas the less-pronounced contrast effect ex vivo is due to its rapid dilution in the inflowing blood. The results confirm weak antiplatelet and anticoagulant influence of NICM in vivo. [ABSTRACT FROM AUTHOR]