Nanotechnology as a Promising Method in the Treatment of Skin Cancer.

The incidence of skin cancer continues to grow. There are an estimated 1.5 million new cases each year, of which nearly 350,000 are melanoma, which is often fatal. Treatment is challenging and often ineffective, with conventional chemotherapy playing a limited role in this context. These disadvantages can be overcome by the use of nanoparticles and may allow for the early detection and monitoring of neoplastic changes and determining the effectiveness of treatment. This article briefly reviews the present understanding of the characteristics of skin cancers, their epidemiology, and risk factors. It also outlines the possibilities of using nanotechnology, especially nanoparticles, for the transport of medicinal substances. Research over the previous decade on carriers of active substances indicates that drugs can be delivered more accurately to the tumor site, resulting in higher therapeutic efficacy. The article describes the application of liposomes, carbon nanotubes, metal nanoparticles, and polymer nanoparticles in existing therapies. It discusses the challenges encountered in nanoparticle therapy and the possibilities of improving their performance. Undoubtedly, the use of nanoparticles is a promising method that can help in the fight against skin cancer.

Impact of Levosimendan and Its Metabolites on Platelet Activation Mechanisms in Patients during Antiplatelet Therapy-Pilot Study.

Levosimendan is used for the short-term treatment of severe heart failure or other cardiac conditions. The area of existing clinical applications for levosimendan has increased significantly. This study aimed to assess whether levosimendan and its metabolites impact the mechanisms related to platelet activation. In this study, we included patients with coronary artery disease receiving antiplatelet therapy. We analyzed the pharmacodynamic profile using three independent methods to assess platelet activity. The results of the conducted studies indicate a mechanism of levosimendan that affects the function of platelets, causing higher inhibition of platelet receptors and, thus, their aggregation. It is essential to clarify whether levosimendan may affect platelets due to the need to maintain a balance between bleeding and thrombosis in patients treated with levosimendan. This is especially important in the case of perioperative bleeding. This study was conducted in vitro; the research should be continued and carried out in patients to check the complete pharmacokinetic and pharmacodynamic profile.

Silver Complexes of Miconazole and Metronidazole: Potential Candidates for Melanoma Treatment.

Melanoma, arguably the deadliest form of skin cancer, is responsible for the majority of skin-cancer-related fatalities. Innovative strategies concentrate on new therapies that avoid the undesirable effects of pharmacological or medical treatment. This article discusses the chemical structures of [(MTZ)2AgNO3], [(MTZ)2Ag]2SO4, [Ag(MCZ)2NO3], [Ag(MCZ)2BF4], [Ag(MCZ)2SbF6] and [Ag(MCZ)2ClO4] (MTZ-metronidazole; MCZ-miconazole) silver(I) compounds and the possible relationship between the molecules and their cytostatic activity against melanoma cells. Molecular Hirshfeld surface analysis and computational methods were used to examine the possible association between the structure and anticancer activity of the silver(I) complexes and compare the cytotoxicity of the silver(I) complexes of metronidazole and miconazole with that of silver(I) nitrate, cisplatin, metronidazole and miconazole complexes against A375 and BJ cells. Additionally, these preliminary biological studies found the greatest IC50 values against the A375 line were demonstrated by [Ag(MCZ)2NO3] and [(MTZ)2AgNO3]. The compound [(MTZ)2AgNO3] was three-fold more toxic to the A375 cells than the reference (cisplatin) and 15 times more cytotoxic against the A375 cells than the normal BJ cells. Complexes of metronidazole with Ag(I) are considered biocompatible at a concentration below 50 µmol/L.

Biological Properties of Extracts Obtained from In Vitro Culture of Plectranthus scutellarioides in a Cell Model.

Plectranthus scutellarioides (L.) R.Br. is a medicinal plant that has long been used in traditional medicine to treat conditions such as abscesses, ulcers, and ear and eye infections. It is known to have a wide range of biological properties, such as antibacterial, antioxidant, antifungal, anti-inflammatory, anti-diabetic and anti-cancer effects. In this study, we established in vitro cultures from both the aerial parts and roots of Plectranthus scutellarioides. Subsequently, we compared the basic phytochemical profile of the obtained extracts and conducted a biological analysis to assess their potential for inducing apoptosis in breast (MCF-7) and lung (A549) cancer cells. Phytochemical analysis by HPLC-MS revealed the presence of compounds belonging to phenolic acids (ferulic, syringic, vanillic, rosmarinic, chlorogenic, caffeic, coumaric, dihydroxybenzoic acids), flavonoids (eriodyctiol and cirsimaritin), and terpenes such as 6,11,12,14,16-Pentahydroxy-3,17diacetyl-8,11,13-abietatrien-7-one, 6,11,12,14,16-Pentahydroxy-3,17-diacetyl5,8,11,13-abietatetraen-7-one, and 3,6,12-Trihydroxy-2-acetyl-8,12-abietadien7,11,14-trione. The results show that both extracts have a cytotoxic and genotoxic effect against MCF-7 and A549 cancer cells, with a different degree of sensitivity. It was also shown that both extracts can induce apoptosis by altering the expression of apoptotic genes (Bax, Bcl-2, TP53, Fas, and TNFSF10), reducing mitochondrial membrane potential, increasing ROS levels, and increasing DNA damage. In addition, it has been shown that the tested extracts can alter blood coagulation parameters. Our results indicate that extracts from in vitro cultures of Plectranthus scutellarioides aerial parts and roots have promising therapeutic application, but further research is needed to better understand the mechanisms of their action in the in vitro model.

Bioinorganic Modulators of Ferroptosis: A Review of Recent Findings.

Ferroptosis was first reported as a separate modality of regulated cell death in 2008 and distinguished under its current name in 2012 after it was first induced with erastin. In the following decade, multiple other chemical agents were researched for their pro- or anti-ferroptotic properties. Complex organic structures with numerous aromatic moieties make up the majority of this list. This review fills a more overlooked niche by gathering, outlining and setting out conclusions regarding less prominent cases of ferroptosis induced by bioinorganic compounds and reported on within the last few years. The article contains a short summary of the application of bioinorganic chemicals based on gallium, several chalcogens, transition metals and elements known as human toxicants used for the purpose of evoking ferroptotic cell death in vitro or in vivo. These are used in the form of free ions, salts, chelates, gaseous and solid oxides or nanoparticles. Knowledge of how exactly these modulators promote or inhibit ferroptosis could be beneficial in the context of future therapies aimed against cancer or neurodegenerative diseases, respectively.

Silver, Its Salts and Application in Medicine and Pharmacy.

The healing properties of silver have been used since ancient times. The main aim of the study was to collect and review the literature on the clinical potential of silver, its salts and complex compounds. The second goal was to present an outline of the historical use of silver in medicine and pharmacy, taking into account the possibility of producing pharmaceutical drug forms on the premises of pharmacies. In the context of the growing resistance of microorganisms to available, widely used antibiotics, silver plays a key role. There is only one known case of bacterial resistance to silver-the Pseudomonas stutzeri strain, which naturally occurs in silver mines. The development of research in the field of coordination chemistry offers great opportunities in the design of new substances in which silver ions can be incorporated. These substances exhibit increased potency and often an extended antimicrobial spectrum. Silver-based compounds are, however, only limited to external applications, as opposed to their historic oral administration. Advanced studies of their physicochemical, microbiological, cytotoxic and genotoxic properties are ongoing and full of challenges. The improvement of the methods of synthesis gives the possibility of applying the newly synthesized compounds ex tempore, as was the case with the complex of metronidazole with silver (I) nitrate. Some of these experimental efforts performed in vitro are followed with clinical trials. The third and final goal of this study was to present the possibility of obtaining an ointment under the conditions of an actual pharmacy using silver (I) salts and a ligand, both of which are active substances with antimicrobial properties.

The Influence of Selected Antipsychotic Drugs on Biochemical Aspects of Alzheimer's Disease.

The aim of this study was to assess the potency of selected antipsychotic drugs (haloperidol (HAL), bromperidol (BRMP), benperidol (BNP), penfluridol (PNF), pimozide (PIM), quetiapine (QUET) and promazine (PROM)) on the main pathological hallmarks of Alzheimer's disease (AD). Binary mixtures of donepezil and antipsychotics produce an anti-BuChE effect, which was greater than either compound alone. The combination of rivastigmine and antipsychotic drugs (apart from PNF) enhanced AChE inhibition. The tested antipsychotics (excluding HAL and PNF) significantly reduce the early stage of Aß aggregation. BRMP, PIM, QUET and PROM were found to substantially inhibit Aß aggregation after a longer incubation time. A test of human erythrocytes hemolysis showed that short-term incubation of red blood cells (RBCs) with QUET resulted in decreased hemolysis. The antioxidative properties of antipsychotics were also proved in human umbilical vein endothelial cells (HUVEC); all tested drugs were found to significantly increase cell viability. In the case of astrocytes, BNP, PNF, PIM and PROM showed antioxidant potential.

Structural Comparison of Sulfonamide-Based Derivatives That Can Improve Anti-Coagulation Properties of Metformin.

Due to its high efficiency, good safety profile, and potential cardio-protective properties, metformin, a dimethyl biguanide, is the first-line medication in antihyperglycemic treatment for type 2 diabetic patients. The aim of our present study was to assess the effects of eight new sulfonamide-based derivatives of metformin on selected plasma parameters and vascular hemostasis, as well as on endothelial and smooth muscle cell function. The compounds with an alkyl chain (1-3), trifluoromethyl substituent (4), or acetyl group (5) significantly elevated glucose utilization in human umbilical endothelial cells (HUVECs), similarly to metformin. Our novel findings showed that metformin analogues 1-3 presented the most beneficial properties because of their greatest safety profile in the WST-1 cell viability assay, which was also proved in the further HUVEC integrity studies using RTCA DP. Compounds 1-3 did not affect either HUVEC or aortal smooth muscle cell (AoSMC) viability up to 3.0 mM. Importantly, these compounds beneficially affected some of the coagulation parameters, including factor X and antithrombin III activity. In contrast to the above-mentioned metformin analogues, derivatives 4 and 5 exerted more profound anticoagulation effects; however, they were also more cytotoxic towards HUVECs, as IC50 values were 1.0-1.5 mM. In conclusion, the chemical modification of a metformin scaffold into sulfonamides possessing alkyl substituents results in the formation of novel derivatives with potential bi-directional activity including anti-hyperglycemic properties and highly desirable anti-coagulant activity.

The Importance of Platelets Response during Antiplatelet Treatment after Ischemic Stroke-Between Benefit and Risk: A Systematic Review.

Ischemic stroke is a disease related to abnormal blood flow that leads to brain dysfunction. The early and late phases of the disease are distinguished. A distinction is made between the early and late stages of the disease, and the best effect in treating an ischemic stroke is usually achieved within the first hours after the onset of symptoms. This review looked at studies platelet activity monitoring studies to determine the risks and benefits of various approaches including antiplatelet therapy. A study was conducted on recently published literature based on PRISMA. This review includes 32 research articles directly addressing the importance of monitoring platelet function during antiplatelet therapy (dual or monotherapy) after ischemic stroke. In patients with transient ischemic attack or ischemic stroke, antiplatelet therapy can reduce the risk of stroke by 11-15%, assuming that patients respond well. Secondary prevention results are dependent on platelet reactivity, meaning that patients do not respond equally to antiplatelet therapy. It is very important that aspirin-resistant patients can benefit from the use of dual antiplatelet therapy. The individualized approach to secondary stroke prevention is to administer the most appropriate drug at the correct dose and apply the optimal therapeutic procedure to the individual patient.

Synaptic Zinc: An Emerging Player in Parkinson's Disease.

Alterations of zinc homeostasis have long been implicated in Parkinson's disease (PD). Zinc plays a complex role as both deficiency and excess of intracellular zinc levels have been incriminated in the pathophysiology of the disease. Besides its role in multiple cellular functions, Zn2+ also acts as a synaptic transmitter in the brain. In the forebrain, subset of glutamatergic neurons, namely cortical neurons projecting to the striatum, use Zn2+ as a messenger alongside glutamate. Overactivation of the cortico-striatal glutamatergic system is a key feature contributing to the development of PD symptoms and dopaminergic neurotoxicity. Here, we will cover recent evidence implicating synaptic Zn2+ in the pathophysiology of PD and discuss its potential mechanisms of actions. Emphasis will be placed on the functional interaction between Zn2+ and glutamatergic NMDA receptors, the most extensively studied synaptic target of Zn2+.

Incorporation of Sulfonamide Moiety into Biguanide Scaffold Results in Apoptosis Induction and Cell Cycle Arrest in MCF-7 Breast Cancer Cells.

Metformin, apart from its glucose-lowering properties, has also been found to demonstrate anti-cancer properties. Anti-cancer efficacy of metformin depends on its uptake in cancer cells, which is mediated by plasma membrane monoamine transporters (PMAT) and organic cation transporters (OCTs). This study presents an analysis of transporter mediated cellular uptake of ten sulfonamide-based derivatives of metformin in two breast cancer cell lines (MCF-7 and MDA-MB-231). Effects of these compounds on cancer cell growth inhibition were also determined. All examined sulfonamide-based analogues of metformin were characterized by greater cellular uptake in both MCF-7 and MDA-MB-231 cells, and stronger cytotoxic properties than those of metformin. Effective intracellular transport of the examined compounds in MCF-7 cells was accompanied by high cytotoxic activity. For instance, compound 2 with meta-methyl group in the benzene ring inhibited MCF-7 growth at micromolar range (IC50 = 87.7 ± 1.18 µmol/L). Further studies showed that cytotoxicity of sulfonamide-based derivatives of metformin partially results from their ability to induce apoptosis in MCF-7 and MDA-MB-231 cells and arrest cell cycle in the G0/G1 phase. In addition, these compounds were found to inhibit cellular migration in wound healing assay. Importantly, the tested biguanides are more effective in MCF-7 cells at relatively lower concentrations than in MDA-MB-231 cells, which proves that the effectiveness of transporter-mediated accumulation in MCF-7 cells is related to biological effects, including MCF-7 cell growth inhibition, apoptosis induction and cell cycle arrest. In summary, this study supports the hypothesis that effective transporter-mediated cellular uptake of a chemical molecule determines its cytotoxic properties. These results warrant a further investigation of biguanides as putative anti-cancer agents.

The Use of Total Thrombus Formation Analysis System as a Tool to Assess Platelet Function in Bleeding and Thrombosis Risk-A Systematic Review.

BACKGROUND: Today there are many devices that can be used to study blood clotting disorders by identifying abnormalities in blood platelets. The Total Thrombus Formation Analysis System is an automated microchip flow chamber system that is used for the quantitative analysis of clot formation under blood flow conditions. For several years, researchers have been using a tool to analyse various clinical situations of patients to identify the properties and biochemical processes occurring within platelets and their microenvironment. METHODS: An investigation of recent published literature was conducted based on PRISMA. This review includes 52 science papers directly related to the use of the Total Clot Formation Analysis System in relation to bleeding, surgery, platelet function assessment, anticoagulation monitoring, von Willebrand factor and others. CONCLUSION: Most available studies indicate that The Total Thrombus Formation Analysis System may be useful in diagnostic issues, with devices used to monitor therapy or as a significant tool for predicting bleeding events. However, T-TAS not that has the potential for diagnostic indications, but allows the direct observation of the flow and the interactions between blood cells, including the intensity and dynamics of clot formation. The device is expected to be of significant value for basic research to observe the interactions and changes within platelets and their microenvironment.

Synaptic zinc contributes to motor and cognitive deficits in 6-hydroxydopamine mouse models of Parkinson's disease.

Hyperactivity of glutamatergic corticostrial pathways is recognized as a key pathophysiological mechanism contributing to development of PD symptoms and dopaminergic neurotoxicity. Subset of corticostriatal projection neurons uses Zn2+ as a co-transmitter alongside glutamate, but the role of synaptically released Zn2+ in PD remains unexplored. We used genetically modified mice and pharmacological tools in combination with 6-hydroxydopamine (6-OHDA) lesion models of PD to investigate the contribution of synaptic zinc to disease associated behavioral deficits and neurodegeneration. Vesicular zinc transporter-3 (ZnT3) knockout mice lacking releasable Zn2+ were more resistant to locomotor deficit and memory impairment of nigrostriatal dopamine (DA) denervation compared to wildtype littermates. The loss of striatal dopaminergic fibers was comparable between genotypes, indicating that synaptically released Zn2+ contributes to behavioral deficits but not neurotoxic effects of 6-OHDA. To gain further insight into the mechanisms of Zn2+ actions, we used the extracellular Zn2+ chelator CaEDTA and knock-in mice lacking the high affinity Zn2+ inhibition of GluN2A-containing NMDA receptors (GluN2A-NMDARs). Acute chelation of extracellular Zn2+ in the striatum restored locomotor deficit of 6-OHDA lesion, confirming that synaptic Zn2+ suppresses locomotor behavior. Disruption of the Zn2+-GluN2A interaction had, on the other hand, no impact on locomotor deficit or neurotoxic effect of 6-OHDA. Collectively, these findings provide clear evidence for the implication of striatal synaptic Zn2+ in the pathophysiology of PD. They unveil that synaptic Zn2+ plays predominantly a detrimental role by promoting motor and cognitive deficits caused by nigrostriatal DA denervation, pointing towards new therapeutic interventions.

Novel halogenated sulfonamide biguanides with anti-coagulation properties.

Apart from its hypoglycaemic properties, metformin also offers beneficial effects for the cardiovascular system resulting in significant reduction of diabetes-related death, and all-cause mortality. The aim of this study was to synthesize nine new benzenesulfonamide derivatives of metformin with a halogen substituent, and estimate their influence on selected parameters of plasma and vascular hemostasis. The study describes the synthesis of nine benzenesulfonamide biguanides with o-, m-, and p- chloro-, bromo-, and fluoro substituents. All orto- derivatives (chloro- (1), bromo- (4), and fluoro- (7)) significantly prolong prothrombin time (PT) and partially activated thromboplastin time (APTT). In addition compounds 4 and 7 slow the process of fibrin polymerization, and contribute to increased TT. Multiparametric CL-test revealed that compounds 1, 4, 7 and p-fluorobenzenesulfonamide (9) significantly prolong the onset of clot formation, decrease initial clot formation velocity, and maximum clotting. Analysis of human endothelial cell (HUVECs) and human aortal smooth muscle cell (AoSMCs) viability over the entire tested concentration range (0.001-3.0 µmol/mL) indicated that the examined compounds can undergo further tests up to 1.5 µmol/mL concentration without decreasing cellular viability. Furthermore, none of the synthesized compounds exert an unfavourable effect on erythrocyte integrity, and thus do not interact strongly with the lipid-protein bilayer. In summary, chemical modification of the metformin backbone into benzenesulfonamides containing halogen substituents at the o- position leads to the formation of potential agents with stronger anti-coagulant properties than the parent drug, metformin. Therefore, o-halogenated benzenesulfonamides can be regarded as an initial promising step in the development of novel biguanide-based compounds with anti-coagulant properties.

Quetiapine and novel PDE10A inhibitors potentiate the anti-BuChE activity of donepezil.

The symptoms of Alzheimer's disease (AD) do not include only memory loss and cognitive decline but also neuropsychiatric manifestation. These AD-related symptoms are usually treated with the aid of antipsychotics; however, their effects on cognition and safety remain unexplored. The present study determines the effects of quetiapine, an atypical antipsychotic, and two imidazo[1,2-a]pyrimidine-based inhibitors of PDE10A on the activity of human cholinesterases. Quetiapine moderately inhibited BuChE (IC50 = 6.08 ± 1.64 µmol/L) but improved the anti-BuChE properties of donepezil by decreasing its IC50 value. Both PDE10A inhibitors were found to possess moderate anti-AChE properties. The combined mixtures of donepezil and imidazo[1,2-a]pyrimidine analogues produce a synergistic anti-BuChE effect which was greater than either compound alone, improving the IC50 value by approximately six times. These favourable interactions between quetiapine, PDE10A inhibitors and clinically approved donepezil, resulting in improved anti-BuChE activity, can lead to a wider variety of potent AD treatment options.

Effective Cellular Transport of Ortho-Halogenated Sulfonamide Derivatives of Metformin Is Related to Improved Antiproliferative Activity and Apoptosis Induction in MCF-7 Cells.

Metformin is a substrate for plasma membrane monoamine transporters (PMAT) and organic cation transporters (OCTs); therefore, the expression of these transporters and interactions between them may affect the uptake of metformin into tumor cells and its anticancer efficacy. The aim of this study was to evaluate how chemical modification of metformin scaffold into benzene sulfonamides with halogen substituents (compounds 1-9) may affect affinity towards OCTs, cellular uptake in two breast cancer cell lines (MCF-7 and MDA-MB-231) and antiproliferative efficacy of metformin. The uptake of most sulfonamides was more efficient in MCF-7 cells than in MDA-MB-231 cells. The presence of a chlorine atom in the aromatic ring contributed to the highest uptake in MCF-7 cells. For instance, the uptake of compound 1 with o-chloro substituent in MCF-7 cells was 1.79 ± 0.79 nmol/min/mg protein, while in MDA-MB-231 cells, the uptake was considerably lower (0.005 ± 0.0005 nmol/min/mg protein). The elevated uptake of tested compounds in MCF-7 was accompanied by high antiproliferative activity, with compound 1 being the most active (IC50 = 12.6 ± 1.2 µmol/L). Further studies showed that inhibition of MCF-7 growth is associated with the induction of early and late apoptosis and cell cycle arrest at the G0/G1 phase. In summary, the chemical modification of the biguanide backbone into halogenated sulfonamides leads to improved transporter-mediated cellular uptake in MCF-7 and contributes to the greater antiproliferative potency of studied compounds through apoptosis induction and cell cycle arrest.

Sulfenamide derivatives can improve transporter-mediated cellular uptake of metformin and induce cytotoxicity in human breast adenocarcinoma cell lines.

Metformin, the most frequently administered oral anti-diabetic drug, is a substrate for organic cation transporters (OCTs). This determines not only its pharmacokinetic properties but also its biochemical effects in humans, including its recently-discovered antiproliferative properties. The aim of the study was to verify the hypothesis whether chemical modification of its biguanide backbone may increase the cellular uptake and antiproliferative efficacy of metformin. The study examines five sulfenamide derivatives of metformin with differing lengths of alkyl chains. It determines their cellular uptake and the role of OCTs in their transport in human breast adenocarcinoma cells (epithelial-like MCF-7, and MDA-MB-231). It also evaluates whether increased cellular uptake of metformin derivatives is associated with their cytotoxic properties. Sulfenamide derivatives were characterized by a greater ability to bind to OCTs than metformin. Compound 2 with n-octyl alkyl chain was found to possess the greatest affinity towards OCTs, as measured by determination of [14C]choline uptake inhibition (IC50 = 236.1 ±â€¯1.28 µmol/L, and 217.4 ±â€¯1.33 µmol/L, for MCF-7 and MDA-MB-231 respectively). Sulfenamides were also found to exhibit better cellular uptake in comparison with the parent drug, metformin. For instance, the uptake of cyclohexyl derivative 1 was 1.28 ±â€¯0.19 nmol/min/mg of proteins and thus was 12-fold higher than the metformin in MCF-7 cells. Furthermore, higher uptake was associated with the greatest antiproliferative properties expressed as the lowest IC50 value i.e. inhibiting the growth of 50% of the cells (IC50 = 0.72 ±â€¯1.31 µmol/L). Collectively, chemical modification of metformin into sulfenamides with different alkyl substituents obtains better substrates for OCTs, and subsequently higher cellular uptake in MCF-7 and MDA-MB-231 cells. Additionally, the length of alkyl chain introduced to the sulfenamides was found to influence selectivity and transport efficiency via OCT1 compared to other possible transporters, as well as potential intracellular activity and cytotoxicity.

Pleiotropic Activity of Metformin and Its Sulfonamide Derivatives on Vascular and Platelet Haemostasis.

As type 2 diabetes mellitus (T2DM) predisposes patients to endothelial cell injury and dysfunction, improvement of vascular function should be an important target for therapy. The aim of this study was to evaluate the effects of metformin, its sulfenamide and sulfonamide derivatives on selected parameters of endothelial and smooth muscle cell function, and platelet activity. Metformin was not found to significantly affect the viability of human umbilical vein endothelial cells (HUVECs) or aortal smooth muscle cells (AoSMC); however, it decreased cell migration by approximately 21.8% in wound healing assays after 24 h stimulation (wound closure 32.5 µm versus 41.5 µm for control). Metformin reduced platelet aggregation manifested by 19.0% decrease in maximum of aggregation (Amax), and 20% reduction in initial platelet aggregation velocity (v0). Furthermore, metformin decreased spontaneous platelet adhesion by 27.7% and ADP-induced adhesion to fibrinogen by 29.6% in comparison to control. Metformin sulfenamide with an n-butyl alkyl chain (compound 1) appeared to exert the most unfavourable effects on AoSMC cell viability (IC50 = 0.902 ± 0.015 µmol/mL), while 4-nitrobenzenesulfonamide (compound 3) and 2-nitrobenzenesulfonamide (compound 4) derivatives of metformin did not affect AoSMC and HUVEC viability at concentrations up to 2.0 µmol/mL. These compounds were also found to significantly reduce migration of smooth muscle cells by approximately 81.0%. Furthermore, sulfonamides 3 and 4 decreased the initial velocity of platelet aggregation by 11.8% and 20.6%, respectively, and ADP-induced platelet adhesion to fibrinogen by 76.3% and 65.6%. Metformin and its p- and o-nitro-benzenesulfonamide derivatives 3, 4 appear to exert beneficial effects on some parameters of vascular and platelet haemostasis.

Scholarly culture: How books in adolescence enhance adult literacy, numeracy and technology skills in 31 societies.

A growing body of evidence supports the contention of scholarly culture theory that immersing children in book-oriented environments benefits their later educational achievement, attainment and occupational standing. These findings have been interpreted as suggesting that book-oriented socialization, indicated by home library size, equips youth with life-long tastes, skills and knowledge. However, to date, this has not been directly assessed. Here, we document advantageous effects of scholarly culture for adult literacy, adult numeracy, and adult technological problem solving. Growing up with home libraries boosts adult skills in these areas beyond the benefits accrued from parental education or own educational or occupational attainment. The effects are loglinear, with greatest returns to the growth in smaller libraries. Our evidence comes from regressions with balanced repeated replicate weights estimated on data from 31 societies which participated in the Programme for the International Assessment of Adult Competencies (PIAAC) between 2011 and 2015.

Assessment of the relationship between platelet reactivity, vascular risk factors and gender in cerebral ischaemia patients.

AIM: Excessive activation and platelet aggregation play important roles in the aetiopathogenesis of cerebral ischaemia. The aim of this study was to assess the relationship between platelet reactivity, gender and vascular risk factors in cerebral ischaemia patients. CLINICAL RATIONALE FOR THE STUDY: The research is useful because we found high risk groups of inefficient aspirin treatment in cerebral ischaemia patients. MATERIAL AND METHODS: The study involved 101 patients, including 69 patients with ischaemic stroke and 32 patients with transient ischaemic attack. The assessment of platelet reactivity was made within 24 hours of the disease onset using two aggregometric methods: impedance and optical. RESULTS: Resistance to acetylsalicylic acid among people with cerebral ischaemia was estimated at 30.69% using impedance aggregometry and 9.2% using optical aggregometry. There were no differences in platelet reactivity or ASA resistance between the groups of patients with stroke and TIA in either method. In the whole group of patients (p = 0.04), and in the group of patients with stroke (p = 0.0143), higher reactivity of platelets was observed by impedance aggregometry in men than in women. In the whole group of patients (p = 0.0229), and in the subgroup with stroke (p = 0.0123), it was shown that aspirin resistance is significantly more common in the subgroup of men than in women. In patients suffering from nicotine addiction, significantly higher platelet reactivity was found in the whole group of patients (p = 0.004), as well as in the subgroup of patients with stroke (p = 0.0135). CONCLUSIONS: There are no differences between platelet reactivity and the incidence of aspirin resistance in patients with stroke and TIA. Male gender and smoking are associated with greater reactivity of platelets and more frequent occurrence of acetylsalicylic acid resistance in patients with cerebral ischaemia. CLINICAL IMPLICATIONS: Dual antiplatelet therapy or clopidogrel treatment should be considered in smoking males with cerebral ischaemia due to the high risk of aspirin inefficiency.