Analgesic and anticonvulsant activity of new derivatives of 2-substituted 4-hydroxybutanamides in mice

Earlier in vitro studies of the compounds marked as GT27, GT28, GT29 and BM128 revealed their inhibitory action towards murine γ-aminobutyric acid (GABA) transporters (mGAT1-mGAT4). In the present paper, the pharmacological activity of four γ-hydroxybutyric acid (GHB) amide derivatives was investigated. The following procedures were involved: locomotor activity, hot plate and electroconvulsive threshold tests. The compounds' influence on motor coordination was evaluated in the chimney test, as well. Intraperitoneal (i.p.) administration of the GHB derivatives decreased animals' locomotor activity (ED(50) values ranged between 23.79 and 26.37 mg/kg). At a dose of 25 mg/kg (i.p.) the compounds prolonged the nociceptive reaction time latency in the hot plate assay to various degree and GT28 and GT29 were the most potent ones in this respect. Their analgesic efficacy was particularly pronounced 30 min after their administration [percent of maximal possible effect (%MPE) = 16.93 and 22.72, respectively]. The investigated GHB derivatives, except for GT29 at 100 mg/kg, increased the electroconvulsive threshold by approximately 4-11 mA as compared to the vehicle-treated mice. In the chimney test they impaired the animals' motor coordination to various degree. We suggest further investigations of the compounds to estimate their biological activity.     

Influence of Amodiaquine on the Antimalarial Activity of Ellagic Acid: Crystallographic and Biological Studies

In the search for new antimalarial drugs, design of hybrid molecules is recommended to improve biological activity and to decrease the risk of parasite resistance development. Ellagic acid, as an inhibitor of Plasmodium glutathione, presents an original mode of action and thus appears as a promising antiplasmodial compound. A new complex (AQ–EA) consisting of the well‐known antimalarial drug, amodiaquine, and ellagic acid was obtained. The studied crystal structure of AQ–EA showed that the triclinic centrosymmetrical unit cell of the crystal contains two molecules of amodiaquine (AQ) and two symmetrically independent molecules of ellagic acid (EA). The packing of the molecules in the crystal is dominated by hydrogen bonds between AQ and EA. The antiplasmodial activity of the hybrid complex AQ–EA was also determined and compared with the values of IC₅₀ for AQ and EA separately. Potentiation assays between both molecules were conducted to understand the pharmacological interactions between AQ and EA against Plasmodium falciparum in vitro. The hybrid complex AQ–EA (IC₅₀ of 47 nm ) showed improved antiplasmodial activity in comparison with EA alone.     

Feasibility and clinical utility of real-time tele-echocardiography using personal mobile device-based pocket echocardiograph

IntroductionRecently introduced microUSB ultrasound probe, which can be connected to personal mobile device constitutes a new class of diagnostic pocket size imaging devices (PSID).The aim of this study was to assess the feasibility and clinical utility of real-time tele-echocardiography with the use such device.Material and methodsThe study group comprised 30 patients (18 men and 12 women; mean age: 54 ±14 years; mean body mass index: 27 ±6 kg/m²), admitted to various hospital departments (infectious diseases, internal medicine and cardiology). All patients underwent focused echocardiographic examination performed by an inexperienced operator using PSID and collaborating remotely in real-time with cardiologist by means of tele-consultation. Before commencing the examination, the operators underwent 1 h training in use of the PSID.ResultsIn most of patients PSID imaging provided sufficient diagnostic image quality. The dimensions of left ventricle, left atrium and the aorta obtained during the this examination showed good correlation with standard echocardiography (r = 0.89, r = 0.82, r = 0.92 respectively), but the correlation for TAPSE measurements was less pronounced (r = 0.52). The agreement in detection of pathologies (wall motion abnormalities, morphological and functional valvular abnormalities) between the tele-echocardiography and standard echocardiographic examination was good to very good (κ ranged from 0.648 to 0.823).ConclusionsPocket size imaging devices allows an inexperienced operator to perform a focused echocardiographic examination under a remote supervision of an experienced cardiologist. The introduction of new technology in the form of PSID with tele-echocardiography feature can revolutionize access to this imaging technique.     

Serum Osteoprotegerin Is an Independent Marker of Left Ventricular Hypertrophy,Systolic and Diastolic Dysfunction of the Left Ventricle and the Presence of Pericardial Fluid in Chronic Kidney Disease Patients

Background: Osteoprotegerin (OPG) is a molecule which belongs to the tumor necrosis factor receptor superfamily. OPG concentration is elevated in patients with left ventricle hypertrophy, heart failure and acute myocardial infarction. OPG concentrations rise in chronic kidney disease (CKD). The aim of this study was to investigate the association between OPG concentrations and cardiovascular complications, such as left ventricle hypertrophy, systolic and diastolic dysfunction of left ventricle and dysfunction of right ventricle in chronic kidney disease patients not treated with dialysis. The relation between OPG and the amount of pericardial fluid was also examined. Methods: One hundred and one men with CKD stage 3–5 not treated with dialysis were included in the study. Overhydration, body fat mass and lean body mass were measured using bioimpedance spectroscopy (BIS). Echocardiography was performed to evaluate the amount of pericardial fluid and to measure the thickness of the interventricular septum (IVS), systolic and diastolic function of left ventricle, as well as systolic function of right ventricle. Results: We observed a significant positive association between OPG and the thickness of the interventricular septum, the size of the left atrium (LA) and the presence of pericardial fluid. A negative relationship was observed between OPG and ejection fraction (EF). Conclusions: Our results suggest that OPG can be an independent marker of left ventricular hypertrophy, systolic and diastolic dysfunction of left ventricle and the presence of pericardial fluid in chronic kidney disease patients.     

Assessment of the Effect of Selenium Supplementation on Production of Selected Cytokines in Women with Hashimoto’s Thyroiditis

The impact of selenium on the course of Hashimoto’s thyroiditis (HT) was mainly assessed by monitoring the titer of antithyroid autoantibodies in most of the studies conducted hitherto. On the other hand, the imbalance in activity of T cells such as Th1, Th2, Th17, and Treg may be relevant in the pathogenesis of this disease. Hence, the assessment of changes in the secretion of cytokines by these cells during selenium supplementation in patients with HT seems to be an important issue and was the main goal of this study. A further aim was to search for correlations among these cytokines, as well as markers of thyroid function, selenium/iodine status in the body, and other biochemical parameters. The group of 29 women with newly diagnosed Hashimoto’s thyroiditis was supplemented with selenium in a dose of 100 µg/day for 6 months. Immunological parameters: interferon γ, tumor necrosis factor α, chemokine CXCL10, interleukin 4, interleukin 1β, interleukin 17, transforming growth factor β, and C-reactive protein, as well as selenium status parameters were determined in serum twice, i.e., before and after supplementation. Selenium supplementation was associated with a change in the production of two cytokines: interferon γ and interleukin 1β, for which a decrease and an increase in concentration were observed, respectively. The partial least squares (PLS) model revealed the presence of many relevant correlations among analyzed parameters. The stage of HT development, degree of thyroid dysfunction, and selenium supplementation of diet are interdependent factors which shape the profile of some cytokines secreted by cells participating in the autoimmunity process.     

Selected Physical and Spectroscopic Properties of TPS Moldings Enriched with Durum Wheat Bran

The impact of the amount of durum wheat bran additive used on the selected structural, mechanical, and spectroscopic properties of thermoplastic starch moldings was examined in this study. Bran was added to corn starch from 10 to 60% by weight in the blends. Four temperature settings were used for the high-pressure injection: 120, 140, 160, and 180 °C. The highest value of elongation at break (8.53%) was observed for moldings containing 60% bran. Moreover, for these moldings, the tensile strength and flexural strength were lower (appropriately 3.43 MPa and 27.14 MPa). The highest deformation at break (1.56%) were obtained for samples with 60% bran and injection molded at 180 °C. We saw that higher bran content (50 and 60%) and a higher injection molding temperature (160 °C and 180 °C) significantly changed the color of the samples. The most significant changes in the FTIR spectra were observed at 3292 and 1644 cm⁻¹ and in the region of 1460–1240 cm⁻¹. Moreover, notable changes were observed in the intensity ratio of bands at 1015 and 955 cm⁻¹. The changes observed correspond well with the amount of additive used and with the injection temperature applied; thus it may be considered as a marker of interactions affecting plasticization of the material obtained.     

Synthesis and antimycobacterial assay of some xanthone derivatives

A series of some derivatives of 2-xanthone was synthesized and evaluated for their activity against M. tuberculosis in primary and/or secondary microbiological assays. The cytotoxic activity of some compounds was also evaluated. The most active compounds were: [I] 2-(2-(4-(2-(4-chloro-3-methylphenoxy)ethyl)piperazin-1-yl)ethoxy)-9H-xanthen-9-one, [III] 2-((4-(2-(4-chlor-3-methylphenoxy)ethyl)piperazin-1-yl)methyl)-9H-xanthen-9-one dihydrochloride and [XVIII] ethyl 4-(2-hydroxy-3-(9-oxo-9H-xanthen-2-yloxy)propyl) piperazine-1-carboxylate, which displayed 98%, 98% and 94% inhibition of M. tuberculosis growth, respectively. Furthermore, compounds III and XVIII revealed their cytotoxic activity (SI < 1). Other structures varied greatly in their anti M. tuberculosis activity, however, several trends in their structure in relation to their antituberculous activity have been observed.     

Trace Element Contents in Petrol-Contaminated Soil Following the Application of Compost and Mineral Materials

The global use of petroleum hydrocarbons as raw materials and an energy source in industry results in serious environmental, health, and ecological problems. Consequently, there is growing interest in the development of technologies for the rehabilitation of contaminated areas. This study was undertaken in order to determine the effect of different phytostabilising materials (compost, bentonite, and CaO) on the trace element content in soil contaminated with unleaded petroleum 95 (0, 2.5, 5, and 10 cm³ kg⁻¹ of soil). The doses of petroleum applied to the soil were based on the previously conducted preliminary experiment. The highest petroleum dose (10 cm³ kg⁻¹ of soil) significantly reduced the chromium, zinc, and cobalt contents in the soil. Petroleum increased the cadmium, lead, nickel, and copper contents in the soil. The materials used for phytostabilisation (compost, bentonite, calcium oxide) had a significant effect on the trace element content in the soil. The application of mineral materials (bentonite and calcium oxide) was more effective than the application of compost, compared to the control series (without soil amendments) as they reduced the contents of cadmium, chromium, nickel, and cobalt in the soil to the greatest extent. The reduction effect of bentonite and calcium oxide on the content of these trace elements in the soil was stronger than compost.