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51.
52.
Agnieszka Zagrska Anna Partyka Adam Bucki Marcin Koaczkowski Magdalena Jastrzbska‐Wisek Anna Czopek Agata Siwek Monika Guch‐Lutwin Marek Bednarski Marek Bajda Jakub Joczyk Kamil Piska Paulina Koczurkiewicz Anna Wesoowska Maciej Pawowski 《Chemical biology & drug design》2019,93(4):511-521
A series of 2‐pyrimidinyl‐piperazinyl‐alkyl derivatives of 1H‐imidazo[2,1‐f]purine‐2,4(3H,8H)‐dione has been synthesized in an attempt to discover a new class of psychotropic agents. Compounds were evaluated for their in vitro affinity for serotonin 5‐HT1A, 5‐HT7, and phosphodiesterases PDE4 and PDE10. The most potent compound 2‐pyrimidinyl‐1‐piperazinyl‐butyl‐imidazo[2,1‐f]purine‐2,4‐dione ( 4b ) behaved as strong and selective antagonist of 5‐HT1A. Molecular modeling studies revealed differences in binding mode between compound 4b and buspirone, which might reflect variation of the ligands’ affinity and potency in the 5‐HT1A receptor. Compound 4b in silico models demonstrated drug‐likeness properties and, contrary to buspirone, showed a metabolic stability in mouse liver microsomes system. Experimentally obtained value of apparent permeability coefficient Papp for 4b in parallel artificial permeability assay indicates the possibility of binding weakly to plasma proteins and high intestinal absorption fraction. Evaluation of the antidepressant‐ and anxiolytic‐like activities of 4b revealed both activities at the same dose of 1.25 mg/kg and seemed to be specific. The antidepressant and/or anxiolytic properties of 4b may be related to its first‐pass effect. 相似文献
53.
Redox state constitutes an important background of numerous liver disorders. The redox state participates in the course of inflammatory, metabolic and proliferative liver diseases. Reactive oxygen species (ROS) are primarily produced in the mitochondria and in the endoplasmic reticulum of hepatocytes via the cytochrome P450 enzymes. Under the proper conditions, cells are equipped with special molecular strategies that control the level of oxidative stress and maintain a balance between oxidant and antioxidant particles. Oxidative stress represents an imbalance between oxidant and antioxidant agents. Hepatocytic proteins, lipids and DNA are among the cellular structures that are primarily affected by ROS and reactive nitrogen species. The process results in structural and functional abnormalities in the liver. Thus, the phenomenon of oxidative stress should be investigated for several reasons. First, it may explain the pathogenesis of various liver disorders. Moreover, monitoring oxidative markers among hepatocytes offers the potential to diagnose the degree of liver damage and ultimately to observe the response to pharmacological therapies. The present report focuses on the role of oxidative stress in selected liver diseases. 相似文献
54.
Nadia Sawicka-Gutaj Aleksandra Klimowicz Jerzy Sowinski Robert Oleksa Maria Gryczynska Anna Wyszomirska Agata Czarnywojtek Marek Ruchala 《Annales d'endocrinologie》2014
Objectives
The aim of the study was to assess the frequency of pyramidal lobe (PL) detected in iodine-131 (I-131) scans of thyroid bed in patients after thyroidectomy for differentiated thyroid cancer (DTC) and to investigate influence of PL on endogenous thyrotropin (TSH) stimulation as well as on the effects of the radio-iodine ablation in one-year follow-up.Patients and methods
This study was designed as a retrospective analysis of 302 radio-iodine neck scans of patients thyroidectomized due to DTC. The study population was selected from patients with PL detected in thyroid bed scintigraphy. Patients without PL were included to the control group. The study and the control groups did not differ in age, sex of patients, histological type and stage of the DTC.Results
Pyramidal lobes were found in 30.5% of all patients. Patients in the study group underwent repeat surgery more often than controls without PL. Preablative TSH level in patients with PL was statistically lower than in the control group, in contrast to free thyroid hormones, which were higher in patients with PL. Preablative and postablative TSH-stimulated thyroglobulin (Tg) and antibodies against thyroglobulin (TgAbs) were measured in both groups, and comparison did not reveal differences. Moreover, for the per-patient analysis, sites of uptake in whole body scintigraphy performed 1 year after radio-iodine remnant ablation (RRA) did not differ between the study and the control groups.Conclusion
Pyramidal lobe decreases endogenous TSH stimulation without impact on radio-iodine therapy outcome in patients with DTC. 相似文献55.
Volkova K Reyhanian N Kot-Wasik A Olsén H Porsch-Hällström I Hallgren S 《General and comparative endocrinology》2012,178(2):282-290
The effects of endocrine disruptors may vary with the timing of exposure. The physiological implications of adult exposure are present during and shortly after exposure while embryonic exposure can imprint changes manifested in adulthood. In this study, guppy (Poecilia reticulata) embryos were exposed to 2 and 20ng/L of 17α-ethinylestradiol during development via the mother and reared in clean water from gestation until 6months of age. As adults, fish exposed to 20ng/L during development showed significantly altered behaviour in the Novel Tank test, where anxiety is determined as the tendency to remain at the bottom upon introduction into an unfamiliar tank. 17α-ethinylestradiol treatment increased the latency time before swimming to the upper half of the tank and decreased the number of transitions to the upper half. In control females the basal stress behaviour responses were significantly higher than in males, as indicated by longer latency period and fewer and shorter visits to the upper half, supporting the importance of gonadal hormones for the behaviour. The anxiety increased, however, with treatment in both sexes, suggesting that the observed response is not entirely due to feminisation of the males. Shoaling behaviour, analysed as tendency to leave a shoal of littermates, was neither sex-differentiated nor changed by treatment. Also male reproductive behaviour, brain aromatase activity and testes histology, previously shown to respond to oestrogen exposure in adult guppy, were unaffected by the developmental treatment. This suggests that the stress system in the guppy is very sensitive to 17α-ethinylestradiol, which possibly causes an early organisational imprint on the brain circuit that regulates stress reactions. 相似文献
56.
We report a case of a 59 year-old patient in a condition of acute myocardial infarction with ST elevation, in a cardiogenic shock, with multiple cardiac arrests in mechanism of ventricular fibrillation with a significant chest wall deformity caused by Heine-Medin disease in childhood. To our knowledge, this is the first case report of a patient in critical condition with a considerable pectus deformity after poliomyelitis who needed to undergo cardiovascular angioplasty. Although severe patient's condition and numerous difficulties during percutaneous coronary intervention, therapy was successful. 相似文献
57.
Inoue M Ebisawa K Itaya T Sugito T Yamawaki-Ogata A Sumita Y Wadagaki R Narita Y Agata H Kagami H Ueda M 《Oral diseases》2012,18(2):206-212
Oral Diseases (2012) 18 , 206–212 Objectives: The effect of growth differentiation factor 5 and bone morphogenetic protein 2 on human periodontal ligament‐derived cells was investigated with special reference to tendo/ligamentogenesis‐related markers. Materials and Methods: Effects of each factor were analyzed by quantitative PCR for scleraxis and tenomodulin and by western blotting for scleraxis. After exposure to those factors, STRO‐1‐positive and STRO‐1‐negative fractions of human periodontal ligament tissues were isolated with an immunomagnetic cell sorting system, and the expression of scleraxis in each fraction was analyzed by western blotting. Non‐separated crude cells were used as a control. Results: Growth differentiation factor 5 and bone morphogenetic protein 2 did not increase alkaline phosphatase activity in crude periodontal ligament‐derived cells. Growth differentiation factor 5, but not bone morphogenetic protein 2, increased the expression of scleraxis in crude, STRO‐1‐positive and STRO‐1‐negative periodontal ligament‐derived cells. The expression of scleraxis in STRO‐1‐positive periodontal ligament‐derived cells was significantly less compared to that in crude P2 and STRO‐1‐negative periodontal ligament‐derived cells. Conclusion: Growth differentiation factor 5 induced the expression of scleraxis and may enhance tendo/ligamentogenesis in human periodontal ligament‐derived cells. The expression of scleraxis was higher in STRO‐1‐negative fraction, suggesting more differentiated state of the cells. 相似文献
58.
59.
Bielecka-Dabrowa A Mikhailidis DP Jones L Rysz J Aronow WS Banach M 《International journal of cardiology》2012,158(1):12-17
Maintenance of normal potassium (K(+)) homeostasis has become an increasingly important limiting factor in the therapy of heart failure (HF). With the application of loop diuretics and digoxin, hypokalemia has become a frequent and feared side effect of treatment. Low serum K(+) in HF may be also a marker of increased neurohormonal activity and disease progression. To gain the maximum benefit from treatment, we need to individualize drug use and carefully monitor electrolytes. Symptomatic HF patients (New York Heart Association class III-IV) should be prescribed the lowest dose of diuretic necessary to maintain euvolemia. Mild hypokalemia may be corrected by the use of aldosterone receptor antagonists such as spironolactone or eplerenone. However, a more severe hypokalemia should preferably be corrected using K(+) supplement. Serum K levels should be frequently checked and maintained between 4.0 and 5.5 mEq/l (mmol/l). 相似文献
60.
Karolina Wojtczak-Soska Tadeusz Pietrucha Agata Sakowicz Malgorzata Lelonek 《Archives of Medical Science》2013,9(1):21-26