Metabolic benefits of 1-(3-(4-(o-tolyl)piperazin-1-yl)propyl)pyrrolidin-2-one : a non-selective α-adrenoceptor antagonist

Purpose Previous studies have shown that several components of the metabolic syndrome, such as hypertension, obesity or imbalanced lipid and carbohydrate homeostasis, are associated with the sympathetic nervous system overactivity. Therefore, the inhibition of the adrenergic nervous system seems to be a reasonable and appropriate therapeutic approach for the treatment of metabolic disturbances. It has been suggested that non-selective adrenoceptor antagonists could be particularly beneficial, since $\alpha$1-adrenoceptor antagonists can improve disrupted lipid and carbohydrate profiles, while the inhibition of the $\alpha$2-adrenoceptor may contribute to body weight reduction. The aim of the present study was to investigate the metabolic benefits deriving from administration of a non-selective $\alpha$-adrenoceptor antagonist from the group of pyrrolidin-2-one derivatives. The aim of the present study was to investigate the potential metabolic benefits deriving from chronic administration o a non-selective $\alpha$-adrenoceptor antagonist, from the group of pyrrolidin-2-one derivatives. Methods The $\alpha$1- and $\alpha$2-adrenoreceptor affinities of the tested compound-1-(3-(4-(o-tolyl)piperazin-1-yl)propyl) pyrrolidin-2-one had been investigated previously by means of the radioligand binding assay. In the present study, we extended the pharmacological profile characteristics of the selected molecule by additional intrinistic activity assays. Next, we investigated the influence of the tested compound on body weight, hyperglycemia, hypertriglyceridemia, blood pressure in the animal model of obesity induced by a highfat diet, and additionally we measured the spontaneous activity and body temperature. Results The intrinistic activity studies revealed that the tested compound is a potent, non-selective antagonist of $\alpha$1B and $\alpha$2A-adrenoceptors. After the chronic administration of the tested compound, we observed reduced level of triglycerides and glucose in the rat plasma. Interestingly, the tested did not reduce the body weight and did not influence the blood pressure in normotensive animals. Additionally, the administration of the tested compound did not change the animals' spontaneous activity and body temperature. Conclusion Non-selective $\alpha$-adrenoceptor antagonist seems to carry potential benefits in the improvement of the reduction of elevated glucose and triglyceride level. The lack of influence on blood pressure suggests that compounds with such a pharmacological profile may be particulary beneficial for the patients with disturbed lipid and carbohydrate profile, who do not suffer from hypertension. These results are particulary valuable, since currently there are no safe $\alpha$2A-adrenoceptor antagonist drugs available in clinical use with the ability to modulate hyperglycemia that would not affect blood pressure

Anticoagulation therapy — the cardiological and neurological point of view

Ustalenie właściwego, czyli skutecznego i bezpiecznego leczenia przeciwkrzepliwego stanowi często złożony, interdyscyplinarny problem. Terapia doustnymi antykoagulantami niebędącymi antagonistami witaminy K, preparatami bezpieczniejszymi i co najmniej tak skutecznymi jak warfaryna stwarza pewne możliwości, nie jest jednak pozbawiona ograniczeń i powikłań. W niniejszej pracy zaprezentowano przypadki pacjentek w wieku 45 i 86 lat, których leczenie wymagało szerokich działań ze strony zarówno neurologów, jak i kardiologów, a dobór odpowiedniej terapii antykoagulacyjnej był trudny.Determining proper, i.e. effective and safe anticoagulant therapy is often complex interdisciplinary problem. New oral anticoagulants are safer and at least as effective as vitamin K antagonists. The therapy with those agents creates some opportunities; however, it is also associated with some limitations and complications. We present the cases of two patients aged 45 and 86 years whose treatment required extensive interventions by both neurologists and cardiologists and in whom the selection of the appropriate anticoagulant therapy was difficult

Dysfunctions in the Mature Dendritic Cells Are Associated with the Presence of Metastases of Colorectal Cancer in the Surrounding Lymph Nodes

Dendritic cells play a key role in the antigen presentation and T cell activation. The aim of this study was a detailed analysis of the presence of mature dendritic cells (CD 83 positive) in colorectal cancer in correlation with selected clinicopathological parameters. The presence of mature dendritic cells (mDCs) was determined immunohistochemically using the anti-CD83 antibody. The morphometric analysis of the mDCs was performed in the normal colon wall adjacent to the cancerous tumor as well as in the front of the tumor and in the main mass of the cancerous tumor. Decrease in mDCs in the front and in the main tumor mass was observed. The increase in the number of mDCs in both of these locations was associated with the presence of metastases in the nearby lymph nodes (p<0.05 and p<0.01). Furthermore, the increase in the proportion of mDCs in the main tumor mass was associated with the presence of the invasion of tumor cells into the blood and lymph vessels (p<0.01). The increase in the amount of mDCs in the cancerous tumor is associated with the invasiveness of the tumor and especially with the metastasis to the surrounding lymph nodes

Tunneling nanotube-mediated intercellular vesicle and protein transfer in the stroma-provided imatinib resistance in chronic myeloid leukemia cells

Intercellular communication within the bone marrow niche significantly promotes leukemogenesis and provides protection of leukemic cells from therapy. Secreted factors, intercellular transfer of mitochondria and the receptor–ligand interactions have been shown as mediators of this protection. Here we report that tunneling nanotubes (TNTs)—long, thin membranous structures, which have been identified as a novel mode of intercellular cross-talk—are formed in the presence of stroma and mediate transfer of cellular vesicles from stroma to leukemic cells. Importantly, transmission of vesicles via TNTs from stromal cells increases resistance of leukemic cells to the tyrosine kinase inhibitor, imatinib. Using correlative light-electron microscopy and electron tomography we show that stromal TNTs contain vesicles, provide membrane continuity with the cell bodies and can be open-ended. Moreover, trans-SILAC studies to reveal the non-autonomous proteome showed that specific sets of proteins are transferred together with cellular vesicles from stromal to leukemic cells, with a potential role in survival and adaptation. Altogether, our findings provide evidence for the biological role of the TNT-mediated vesicle exchange between stromal and leukemic cells, implicating the direct vesicle and protein transfer in the stroma-provided protection of leukemic cells

[Methylhydrazinium]2PbBr4, a ferroelectric hybrid organic-inorganic perovskite with multiple nonlinear optical outputs

An expansive library of structurally complex two-dimensional (2D) and three-dimensional (3D) lead halide perov-skites has emerged over the past decade, finding applications in various aspects of photon management: photovoltaics, photo-detection, light emission, and nonlinear optics. Needless to say, the highest degree of structural plasticity enjoys the former group, offering a rich playground for modifications of relevant optoelec-tronic parameters such as exciton energy. Structural tailorability is reflected in the ease of modification of the chemistry of the organic layers residing between inorganic slabs. In this vein, we show that the introduction of methylhydrazinium cation (MHy+, CH3NH2NH2+) into 2D perovskite gives a material with a record low separation of the inorganic layers (8.91 Å at 300 K). Optical studies showed that MHy2PbBr4 features the most red-shifted excitonic absorption among all known A2PbBr4 compounds as well as a small exciton binding energy of 99.9 meV. MHy2PbBr4 crystallizes in polar Pmn21 symmetry at room emperature (phase III) and at 351 K undergoes a phase transition to modulated Pmnm phase (II) followed by another phase transition at 371 K to Pmnm phase (I). The ferroelectric property of room-temperature phase III is inferred from switching of the pyrocurrent, dielectric measurements, and optical birefringence results. MHy2PbBr4 exhibits multiple nonlinear optical phenomena such as second-harmonic generation, third-harmonic generation, two-photon excited luminescence, and multiphoton excited luminescence. Analysis of MHy2PbBr4 single-crystal luminescence spectra obtained through linear and nonlinear optical excitation pathways indicates that free exciton emission is readily probed by the ultraviolet excitation, whereas crumpled exciton emission is detected under two- and multiphoton excitation conditions. Overall, our results demonstrate that incorporation of MHy+ into the organic layer is an emergent strategy for obtaining a 2D perovskite with polar character and multifunctional properties

The Influence of Selected Meteorological Factors on the Prevalence and Course of Stroke

Background: The objective of this study was to evaluate the impact of weather factors on stroke parameters. Methods: This retrospective study analyzed the records of stroke patients concerning the influence of meteorological conditions and moon phases on stroke parameters. Results: The study group consisted of 402 patients aged between 20 and 102; women constituted 49.8% of the subjects. Ischaemic stroke was diagnosed in 90.5% of patients and hemorrhagic stroke was diagnosed in 9.5% of patients. The highest number of hospitalizations due to stroke was observed in January (48 events); the lowest number was observed in July (23 events). There was no statistically significant correlation between the meteorological parameters on the day of onset and the preceding day of stroke and the neurological status (NIHSS) of patients. Mean air temperature on the day of stroke and the day preceding stroke was significantly lower in the group of patients discharged with a very good functional status (≤2 points in modified Rankin scale (mRS)) compared to the patients with a bad functional status (&gt;2 points in mRS); respectively: 7.98 ± 8.01 vs. 9.63 ± 7.78; p = 0.041 and 8.13 ± 7.72 vs. 9.70 ± 7.50; p = 0.048). Humidity above 75% on the day of stroke was found to be a factor for excellent functional state (RR 1.61; p = 0.016). The total anterior circulation infarcts (in comparison with stroke in the other localization) were more frequent (70%) during a third quarter moon (p = 0.011). The following parameters had a significant influence on the number of stroke cases in relation to autumn having the lowest number of onsets: mean temperature (OR 1.019 95% CI 1.014–1.024, p &lt; 0.000), humidity (OR 1.028, CI 1.023–1.034, p &lt; 0.0001), wind speed (OR 0.923, 95% CI 0.909–0.937, p &lt; 0.0001), insolation (OR 0.885, 95% CI 0.869–0.902, p &lt; 0.0001), precipitation (OR 0.914, 95% CI 0.884–0.946, p &lt; 0.0001). Conclusion: Air humidity and air temperature on the day of stroke onset as well as air temperature on the day preceding stroke are important for the functional status of patients in the acute disease period. A combination of the following meteorological parameters: lowered mean temperature and low sunshine, high humidity and high wind speed all increase the risk of stroke during the winter period. High humidity combined with high precipitation, low wind speed and low sunshine in the autumn period are associated with the lowest stroke incidence risk. A possible relationship between phases of the moon and the incidence requires further investigation

Plotyn in Porphyrius's creation

Celem pracy było zatem wykazanie, że Plotyn budził podziw u swego ucznia Porfiriusza, był dla niego przewodnikiem świadomości. Uczeń wpatrzony zaś był bezgranicznie w swego mistrza. Plotyn swoim życiem udowodnił, że realizowanie jego filozofii w życiu codziennym pozwala przezwyciężyć wszelkie ludzkie udręki. W niniejszej pracy podjęto również próbę przedstawienia Plotyna od strony czysto ludzkiej, a także próbę odpowiedzi na pytanie, kim i jaki był Plotyn jako człowiek. Choć filozof był raczej niechętny cielesności i indywidualności podjęto próbę ukazania, czy w ogóle istnieją i jakie są jego cechy indywidualne.Porphyry of Tyre – Plotinus’ student – edited his professor’s biography which contains recollection of discourse with the philosopher and description of his personality.In his life and philosophy, Plotinus expressed reluctance to everything connected with carnality and sensuality while admired abstract values.In the time he lived and nowadays, he is an original philosopher continuing a tradition of considering philosophy as art of life, attitude towards spirituality. His life was filled with pursuit of realizing the philosophy.Plotinus was characterized by restraint, moderation, openness, power of the spirit, strength of character, gentleness, kindness and simplicity