The Antiarrhythmic and Hypotensive Effects of S-61 and S-73, the Pyrrolidin-2-one Derivatives with α1-Adrenolytic Properties

Heart rhythm abnormalities are a cause of many deaths worldwide. Unfortunately, the available antiarrhythmic drugs show limited efficacy and proarrhythmic potential. Thus, efforts should be made to search for new, more effective, and safer pharmacotherapies. Several studies suggested that blocking the α₁-adrenoceptors could restore normal heart rhythm in arrhythmia. In this study, we aimed to assess the antiarrhythmic potential of S-61 and S-73, two novel pyrrolidin-2-one derivatives with high affinity for α₁-adrenergic receptors. First, using radioligand binding studies, we demonstrated that S-61 and S-73 did not bind with β₁-adrenoceptors. Next, we assessed whether S-61 and S-73 could protect rats against arrhythmia in adrenaline-, calcium chloride- and aconitine-induced arrhythmia models. Both compounds showed potent prophylactic antiarrhythmic properties in the adrenaline-induced arrhythmia model, but the effect of S-61 was more pronounced. None of the compounds displayed antiarrhythmic effects in calcium chloride- or aconitine-induced arrhythmia models. Interestingly, both derivatives revealed therapeutic antiarrhythmic activity in the adrenaline-induced arrhythmia, diminishing heart rhythm irregularities. Neither S-61 nor S-73 showed proarrhythmic potential in rats. Finally, the compounds decreased blood pressure in rodents. The hypotensive effects were not observed after coadministration with methoxamine, which suggests the α₁-adrenolytic properties of both compounds. Our results confirm that pyrrolidin-2-one derivatives possess potent antiarrhythmic properties. Given the promising results of our experiments, further studies on pyrrolidin-2-one derivatives might result in the development of a new class of antiarrhythmic drugs.     

A Scoping Analysis of Cathelicidin in Response to Organic Dust Exposure and Related Chronic Lung Illnesses

Over two billion people worldwide are exposed to organic dust, which can cause respiratory disorders. The discovery of the cathelicidin peptide provides novel insights into the lung’s response to organic dust; however, its role in the lung’s response to organic dust exposure and chronic lung diseases remains limited. We conducted a scoping review to map the current evidence on the role of cathelicidin LL-37/CRAMP in response to organic dust exposure and related chronic lung diseases: hypersensitivity pneumonitis (HP), chronic obstructive pulmonary disease (COPD) and asthma. We included a total of n = 53 peer-reviewed articles in this review, following the process of (i) a preliminary screening; (ii) a systematic MEDLINE/PubMed database search; (iii) title, abstract and full-text screening; (iv) data extraction and charting. Cathelicidin levels were shown to be altered in all clinical settings investigated; its pleiotropic function was confirmed. It was found that cathelicidin contributes to maintaining homeostasis and participates in lung injury response and repair, in addition to exerting a positive effect against microbial load and infections. In addition, LL-37 was found to sustain continuous inflammation, increase mucus formation and inhibit microorganisms and corticosteroids. In addition, studies investigated cathelicidin as a treatment modality, such as cathelicidin inhalation in experimental HP, which had positive effects. However, the primary focus of the included articles was on LL-37’s antibacterial effect, leading to the conclusion that the beneficial LL-37 activity has not been adequately examined and that further research is required.     

Distinct Influence of Saturated Fatty Acids on Malignant and Nonmalignant Human Lung Epithelial Cells

The impact of saturated fatty acids (FA) on viability and properties of malignant and nonmalignant cells has not been studied in detail so far. The present study was aimed at evaluation of the influence of saturated FA (10:0–18:0) on malignant (A459) and nonmalignant (BEAS-2B) human lung epithelial cells. FA strongly affected A549 cells, but not BEAS-2B cells. Viability of A549 cells incubated with 14:0–18:0 was decreased by 53–91% as compared to untreated cells. Cell membrane stiffness in those cells as measured by atomic force microscopy was also reduced. Median value of apparent Young's modulus of untreated A549 cell membrane was 16.9 kPa and it decreased to 8.9 kPa for cells incubated with 14:0. Viability and mechanical properties of BEAS-2B cells were not altered by presence of FA. Those surprising discrepancies can be related to the differences in FA uptake rate. A549 cells were found to incorporate higher amount of FA and this corresponded to decrease in cell membrane stiffness and reduced cell viability. The performed studies showed that saturated FA have distinct influence on various types of cells, which may be exploited in development of the advanced lipid drug delivery systems.     

How Antidepressant Drugs Affect the Antielectroshock Action of Antiseizure Drugs in Mice: A Critical Review

Depression coexists with epilepsy, worsening its course. Treatment of the two diseases enables the possibility of interactions between antidepressant and antiepileptic drugs. The aim of this review was to analyze such interactions in one animal seizure model—the maximal electroshock (MES) in mice. Although numerous antidepressants showed an anticonvulsant action, mianserin exhibited a proconvulsant effect against electroconvulsions. In most cases, antidepressants potentiated or remained ineffective in relation to the antielectroshock action of classical antiepileptic drugs. However, mianserin and trazodone reduced the action of valproate, phenytoin, and carbamazepine against the MES test. Antiseizure drug effects were potentiated by all groups of antidepressants independently of their mechanisms of action. Therefore, other factors, including brain-derived neurotrophic factor (BDNF) and glial-derived neurotrophic factor (GDNF) modulation, should be considered as the background for the effect of drug combinations.     

The Reduction and Oxidation of Co Species in CoZSM-5 Zeolites Studied by IR Spectroscopy

The process of reducing Co ions in zeolite CoZSM-5 by NO, H₂ and CO, as well as of oxidizing them by O₂ was studied by IR spectroscopy with CO as the probe molecule for Co²⁺ and NO as the probe for Co³⁺. Two zeolites of different Co status were used: in the first, Co²⁺ ions were localized mostly in cation exchange positions, and in the second most of the Co²⁺ occurred in the form of CoO and oxide-like clusters. IR studies evidenced that NO reduced some Co³⁺ to Co²⁺ already at room temperature, and also reduced some Co²⁺ to lower oxidation states (probably Co⁺) at 670 and 1070 K. Only Co²⁺ in exchange positions could be reduced with NO. The treatment of zeolite CoZSM-5 with H₂ or with CO at 670 and 1070 K made the reduction of Co³⁺ to Co²⁺ (the contribution of Co³⁺ decreased and the contribution of Co²⁺ increased). IR studies illustrated that the most electron-acceptor Co³⁺ (characterized by a high frequency Co³⁺–NO band) were transformed, by reduction, into the most electron-acceptor Co²⁺ (characterized by a high frequency Co²⁺–CO band). The treatment of zeolite CoZSM-5 with oxygen at 670–1070 K resulted in the oxidation of Co²⁺ to Co³⁺ (the contribution of Co²⁺ decreased while the contribution of Co³⁺ increased).     

Comparative risk assessment of residential radon exposures in two radon-prone areas, ?tei (Romania) and Torrelodones (Spain)

Radon and radon progeny are present indoors, in houses and others dwellings, representing the most important contribution to dose from natural sources of radiation. Most studies have demonstrated an increased risk of lung cancer at high concentration of radon for both smokers and nonsmokers. The work presents a comparative analysis of the radon exposure data in the two radon-prone areas, ?tei, Transylvania, (Romania), in the near of old Romanian uranium mines and in the granitic area of Torrelodones town, Sierra de Guadarrama (Spain). Measurements of indoor radon were performed in 280 dwellings (Romania) and 91 dwellings (Spain) by using nuclear track detectors, CR 39. The highest value measured in ?tei area was 2650 Bq m^− 3 and 366 Bq m^− 3 in the Spanish region. The results are computed with the BEIR VI report estimates using the age-duration model at an exposure rate below 2650 Bq m^− 3. We used the EC Radon Software to calculate the lifetime lung cancer death risks for individuals groups in function of attained age, radon exposures and tobacco consumption. A total of 233 lung cancer deaths were observed in the ?tei area for a period of 13 years (1994-2006), which is 116.82% higher than expected from the national statistics. In addition, the number of deaths estimated for the year 2005 is 28, which is worth more than 2.21 times the amount expected by authorities. In comparison, for Torrelodones was rated a number of 276 deaths caused by lung cancer for a period of 13 years, which is 2.09 times higher than the number expected by authorities. For the year 2005 in the Spanish region were reported 32 deaths caused by pulmonary cancer, the number of deaths exceeding seen again with a factor of 2.10 statistical expectations. This represents a significantly evidence that elevated risk can strongly be associated with cumulated radon exposure.     

Indirect,non-competitive amperometric immunoassay for accurate quantification of calpastatin,a meat tenderness marker,in bovine muscle

A method is described for quantification of the beef tenderness marker, calpastatin, in meat samples by amperometric detection. Using a novel bovine recombinant partial calpastatin protein as standard antigen a low detection limit of 0.2 ng/mL was achieved. The influence of the complex matrix was minimised by heat pretreatment and dilution of the samples prior to detection of calpastatin. The relative error between the direct sample measurement and standard addition methods was 5.89%, confirming the accuracy of the developed amperometric immunoassay.     

Stresses Generated During Convective and Microwave Drying

An outline of the mechanistic model of convective and microwave drying of saturated capillary-porous materials is presented. The model was derived in the framework of irreversible thermodynamics. Particular attention is devoted to construction of the term describing the power of microwave radiation absorbed per unit volume, which is converted into internal heat source. The qualitative difference in distribution of temperature, moisture content, and the drying-induced stresses in materials under convective and microwave drying is illustrated in the examples of cylindrical kaolin samples. The diagrams of acoustic emission are taken off on-line from these samples in order to illustrate the development of material destruction caused by the stresses induced during both convective and microwave drying.