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The process of platelet aggregation is often influenced by several factors including sex and age. A literature review confirmed the existence of sex-related differences in platelet aggregation. Although 68 out of 78 papers found such differences, there are still some controversies regarding these differences, which can be due to multiple factors (age, trigger, concomitant disease, sample handling, etc.). These outcomes are discussed in line with novel results obtained from a local study, in which blood samples from a total of 53 overall healthy women and men with ages ranging from 20 to 66 years were collected. Aggregation was induced with seven different triggers (ristocetin, thrombin receptor activating peptide 6 [TRAP-6], arachidonic acid [AA], platelet-activating factor 16 [PAF-16], ADP, collagen, or thromboxane A 2 analog U-46619) ex vivo. In addition, three FDA-approved antiplatelet drugs (vorapaxar, ticagrelor, or acetylsalicylic acid [ASA]) were also tested. In general, women had higher aggregation responses to some agonists (ADP, TRAP), as well as lower benefit from inhibitors (ASA, vorapaxar). The aggregatory responses to AA and TRAP decreased with age in both sexes, while responses to ADP, U-46619, and PAF were affected by age only in women. In conclusion, more studies are needed to decipher the biological importance of sex-related differences in platelet aggregation in part to enable personalized antiplatelet treatment. [ABSTRACT FROM AUTHOR]

Objectives Both pyridine and pyrano derivatives have been previously shown to possess biologically relevant activity. In this study, we report the incorporation of these two scaffolds into one molecule. Methods The designed 3,3-dimethyl-6-oxopyrano[3,4- c ]pyridines were synthesized by the acylation of enamine under Stork conditions followed by condensation of formed β-diketones with 2-cyanoacetamide. The structures of these compounds were confirmed by using a wide spectrum of physico-chemical methods. Their antiplatelet, anticoagulant and vasodilatory activity together with toxicity were evaluated. Key findings A series of 6-oxopyrano[3,4- c ]pyridines 3a–j was obtained. Four of these compounds were reported for the first time. None of the tested compounds demonstrated anticoagulant effect but 8-methyl derivative (3a) was a potent antiplatelet compound with IC50 numerically twice as low as the clinically used acetylsalicylic acid. A series of further mechanistic tests showed that 3a interferes with calcium signaling. The compound is also not toxic and in addition possesses vasodilatory activity as well. Conclusions Compound 3a is a promising inhibitor of platelet aggregation, whose mechanism of action should be studied in detail. [ABSTRACT FROM AUTHOR]

The process of platelet aggregation is often conditioned by personal circumstances such as age, gender, lifestyle, and the presence of concomitant diseases. An additional factor is the resistance to current antiplatelet drugs developed by some patients, although the reason is not always obvious. In this work, we enrolled a total of 53 overall healthy women and men donors with ages ranging from 20 to 66 years for a cross-sectional study. Blood samples were taken, and aggregation was induced with a total of seven different compounds (ristocetin, thrombin receptor activating protein-6 [TRAP], arachidonic acid [AA], platelet activating factor-16 [PAF], ADP, collagen, or thromboxane A2 analogue U46619) ex vivo. In addition, some samples were pretreated with clinically used antiplatelet drugs (vorapaxar, ticagrelor, or acetylsalicylic acid [ASA]). Our results showed a pattern in which increasing age decreased the aggregatory responses to AA and TRAP in both genders, whereas responses to ADP, U-46619, and PAF were affected by age only in women. In addition, women had stronger responses to some aggregation inducers (ADP, TRAP), as well as lower benefit from antiplatelet drugs (ASA, vorapaxar). Physiological levels of blood lipids and glucose, as well as body mass index, had mostly no effect on platelet aggregation in this study. On the contrary, several strong positive correlations between different aggregation triggers were observed. The different responses in women, in relation to age, are of note for future studies. [ABSTRACT FROM AUTHOR]

This review summarizes the current knowledge on essential vitamins B1, B2, B3, and B5. These B-complex vitamins must be taken from diet, with the exception of vitamin B3, that can also be synthetized from amino acid tryptophan. All of these vitamins are water soluble, which determines their main properties, namely: they are partly lost when food is washed or boiled since they migrate to the water; the requirement of membrane transporters for their permeation into the cells; and their safety since any excess is rapidly eliminated via the kidney. The therapeutic use of B-complex vitamins is mostly limited to hypovitaminoses or similar conditions, but, as they are generally very safe, they have also been examined in other pathological conditions. Nicotinic acid, a form of vitamin B3, is the only exception because it is a known hypolipidemic agent in gram doses. The article also sums up: (i) the current methods for detection of the vitamins of the B-complex in biological fluids; (ii) the food and other sources of these vitamins including the effect of common processing and storage methods on their content; and (iii) their physiological function. [ABSTRACT FROM AUTHOR]

Background: Cobalt is an essential trace element, but it can also rarely cause cobalt toxicity due to its release from cobalt-containing medical devices. Currently, there are no approved selective cobalt chelators, which would represent an optimal treatment modality., Objective: This study aimed to develop a simple and complex methodological approach for screening potential cobalt chelators and evaluating their potential toxicity., Methods: Firstly, a simple spectrophotometric assay employing 1-nitroso-2-naphthol-3,6- disulfonic acid disodium salt (NNDSA) for screening cobalt chelation was standardized at a pathophysiologically relevant range of pH 4.5-7.5. Then, the suitability of the method was verified using four known metal chelators (EDTA, 8-hydroxyquinoline, chloroxine and nitroxoline). As cobalt can catalyse the Fenton reaction, the potential toxicity of cobalt-chelator complexes was also determined by employing a novel HPLC method with coulometric detection. The effect on erythrocyte haemolysis was tested as well., Results: The NNDSA method had high sensitivity enabling the detection of 25-200 nM of cobalt ions depending on pH conditions. Measurements could be carried out in a wide range of wavelengths from 470 to 540 nm. All tested complexes of the selected chelators decreased the rate of the Fenton reaction. Interestingly, chloroxine mixed with cobalt ions caused marked lysis of erythrocytes in contrast to the other compounds., Conclusion: The described complex methodological approach could serve as a simple yet precise tool for evaluating novel, effective and safe cobalt chelators., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Antiplatelet drugs represent the keystone in the treatment and prevention of diseases of ischemic origin, including coronary artery disease. The current palette of drugs represents efficient modalities in most cases, but their effect can be limited in certain situations or associated with specific side effects. In this study, representatives of compounds selected from series having scaffolds with known or potential antiplatelet activity were tested. These compounds were previously synthetized by us, but their biological effects have not yet been reported., Objective: The aim of this study was to examine the antiplatelet and anticoagulation properties of selected compounds and determine their mechanism of action., Methods: Antiplatelet activity of compounds and their mechanisms of action were evaluated using human blood by impedance aggregometry and various aggregation inducers and inhibitors and compared to appropriate standards. Cytotoxicity was tested using breast adenocarcinoma cell cultures and potential anticoagulation activity was also determined., Results: In total, four of 34 compounds tested were equally or more active than the standard antiplatelet drug Acetylsalicylic Acid (ASA). In contrast to ASA, all 4 active compounds decreased platelet aggregation triggered not only by collagen, but also partly by ADP. The major mechanism of action is based on antagonism at thromboxane receptors. In higher concentrations, inhibition of thromboxane synthase was also noted. In contrast to ASA, the tested compounds did not block cyclooxygenase- 1., Conclusion: The most active compound, 2-amino-4-(1H-indol-3-yl)-6-nitro-4H-chromene-3- carbonitrile (2-N), which is 4-5x times more potent than ASA, is a promising compound for the development of novel antiplatelet drugs., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)