On the respiratory function of human blood platelets

A set of physiological parameters of the blood from healthy individuals and patients with hypochromic anemia was subjected to factor analysis in order to test the hypothesis that platelets perform a respiratory function in circulation. Platelets were shown to have no respiratory function comparable to that of erythrocytes; however, the state of the pool of circulating platelets was of significance for blood gas exchange and rheology. When interpreting the extracted factors and observing the type, strength, and dynamics of the correlations found, we suggested that the effects of platelets on blood gas exchange and rheology were indirect, mediated by the platelet pool of biologically active substances. Being involved in the regulation of microcirculation and vessel wall permeability, platelets modulate the erythrocyte transport function.     

Proton NMR studies of nucleotide and amine storage in the dense granules of pig platelets

1H NMR measurements have been conducted at 360 MHz on isolated pig platelet dense granules. Resonances of the H8, H2 protons of the adenine ring, H1' protons of the ribose moiety, and the aromatic hydrogens of 5-hydroxytryptamine (5HT) have been identified in spectra of intact dense granules. Like the 31P resonances of the nucleotides contained in the dense granules (U?urbil et al., 1984), the line widths and the intensities of these resonances were sensitive to sample temperature and osmolarity of the suspension medium. Their chemical shifts indicate that 5HT in the granule interior is predominantly bound to the nucleotides through ring-stacking interactions. Association of 5HT with the nucleotides was also confirmed by the presence of intermolecular nuclear Overhauser effect (NOE) between 5HT and nucleotide protons. Large and negative intermolecular NOE's observed among the nucleotide H8, H2 and H1' protons, together with upfield shifts undergone by these protons within the dense granules, demonstrate that the nucleotides form a complex where they are in close proximity of each other. The formation of this complex apparently does not require the presence of amines since removal of 5HT and histamine did not change the chemical shifts of the nucleotide protons. From T1 and T2 data, rotational correlation time of 4 ns was calculated for the nucleotides in the dense granule interior at 35 degrees C. A resonance tentatively identified as H2 of histamine was found to shift upon manipulation of the intragranular pH; it was used as an indicator of pH changes within the granule interior during 5HT uptake and showed that 5HT accumulation increases the intragranular pH. These results demonstrate that 5HT is first taken up in response to the inside acidic pH gradient across the granule membrane and is subsequently sequestered in a matrix formed by the divalent cations and the nucleotides.     

Antimalarial drugs impact chemical messenger secretion by blood platelets

BackgroundAdvances in antimalarial drug development are important for combating malaria. Among the currently identified antimalarial drugs, it is suggested that some interact directly with the malarial parasites while others interact indirectly with the parasites. While this approach leads to parasite elimination, little is known about how these antimalarial drugs impact immune cells that are also critical in malarial response.MethodsHerein, the effects of two common antimalarial drugs, chloroquine and quinine, on platelets were explored at both the bulk level, using high performance liquid chromatography, and the single cell level, using carbon-fiber microelectrode amperometry, to characterize any changes in chemical messenger secretion.ResultsThe data reveal that both drugs cause platelet activation and reduce the number of platelet exocytosis events as well as delay fusion pore opening and closing.ConclusionsThis work demonstrates how chloroquine and quinine quantitatively and qualitatively impact in vitro platelet function.General significanceOverall, the goal of this work is to promote understanding about how antimalarial drugs impact platelets as this may affect antimalarial drug development as well as therapeutic approaches to treat malarial infection.     

The in vitro effect of pirprofen on the surface ultrastructure and function of human platelets

The in vitro effect of pirprofen (Rengasil), an antiinflammatory agent, on the surface ultrastructure and function of human platelets was examined and compared with that of acetylsalicylic acid (Aspirin, ASA), and diclofenac sodium (Voltaren, DS). Incubation with pirprofen induced formation of long, needle-shaped pseudopodia, a phenomenon observed also after incubation of the cells with DS. In contrast with ASA and DS, pirprofen induced a marked increase in platelet protein synthesizing capacity. The drug decreased the platelet aggregation to a degree similar to that of ASA and DS. The release of platelet factors 3 and 4 and the level of beta-thromboglobulin following incubation with the drug remained unaltered.     

Usefulness of determining conjugated amine catecholamines in blood platelets for diagnosis of pheochromocytoma]

The studies included 14 patients with pheochromocytoma (mean age 39.5 years), 32 patients with arterial hypertension (mean age 39.5 years), and 9 healthy volunteers (mean age 39.5 years). Free and conjugated noradrenaline and adrenaline in blood platelets have been assayed with RIA technique. It was shown that mean concentrations of conjugated noradrenaline and adrenaline in blood platelets are significantly higher in patients with pheochromocytoma than those in hypertensive patients and healthy individuals. However, such test may be used with limitations as there is high percentage of increased values in patients with the primary arterial hypertension. A decreased noradrenaline inactivation in blood platelets of patients with pheochromocytoma has also been observed. This may exert some effect on the diversified clinical course of this type of arterial hypertension.     

The effect of colchicine on human blood platelets under conditions of short-term incubation.

The effects of colchicine on ADP-induced aggregation and on the phosphorylation of tubulin-like protein from human blood platelets were studied. Colchicine at 2mM concentration completely inhibits ADP-induced aggregation after 8min incubation. Under the same inhibitory conditions, phosphorylation of tubulin-like materials in intact platelets was also impaired whereas the endogenous kinase activity of tubulin, isolated through polymerization--depolymerization cycles, was not affected. It was also shown that, under conditions of maximal inhibition of both aggregation and tubulin phosphorylation, colchicine does not penetrate into the cells. The results obtained suggest that the effect of colchicine on platelet aggregation might be mainly, although not exclusively, due to a non-specific effect of the alkaloid on the plasma membrane, rather than to a direct action of the drug on the microtubular protein subunits.     

The effect of storage on whole blood chemiluminescence measurement of equine neutrophils

The aim of this study was to determine the effect of duration and temperature of sample storage on whole blood chemiluminescence measurement results. Venous blood from 18 clinically healthy Polish half‐bred horses aged 4 to 11 years were used in the study. Luminol dependent chemiluminescence (CL) was used to measure neutrophil oxygen metabolism in whole blood. Blood samples were examined for spontaneous CL and stimulated by a surface receptor stimulus as well as extra‐receptor stimulus. The assay was performed in two parallel experimental sets with samples stored at 4 and 22 °C, respectively. Whole blood CL was estimated at 2, 6, 24, 48, 72, 96 and 120 h after collection. The study demonstrated that temperature and duration of sample storage are factors that determine the quality of CL measurements of whole blood in horses. The study concluded that samples should be stored at 4 °C and the assay should be performed as early as possible. It was also shown that the viability period of horse blood for CL assays is relatively long. Material stored at room temperature for 24 h and even up to 48 h at 4 °C did not show any significant decrease in spontaneous or stimulated chemiluminescence. Copyright © 2012 John Wiley & Sons, Ltd.