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Tomasz Bartosik Joanna Drogosz-Stachowicz Anna Janecka Jacek Kdzia Barbara Pacholczyk-Sienicka Jacek Szymaski Katarzyna Gach-Janczak Tomasz Janecki 《Materials》2022,15(9)
In this report, we present efficient and stereoselective syntheses of 2,6-disubstituted trans-3-methylidenetetrahydropyran-4-ones and 2-(4-methoxyphenyl)-5-methylidenetetrahydropyran-4-one that significantly broaden the spectrum of the available methylidenetetrahydropyran-4-ones with various substitution patterns. Target compounds were obtained using Horner–Wadsworth–Emmons methodology for the introduction of methylidene group onto the pyranone ring. 3-Diethoxyphosphoryltetrahydropyran-4-ones, which were key intermediates in this synthesis, were prepared by fully or highly stereoselective addition of Gilman or Grignard reagents to 3-diethoxyphosphoryldihydropyran-4-ones. Addition occurred preferentially by axial attack of the Michael donors on the dihydropyranone ring. Relative configurations and conformations of the obtained adducts were assigned using a detailed analysis of the NMR spectra. The obtained methylidenepyran-4-ones were evaluated for cytotoxic activity against two cancer cell lines (HL-60 and MCF-7). 2,6-Disubstituted 3-methylidenetetrahydropyran-4-ones with isopropyl and phenyl substituents in position 2 were more cytotoxic than analogs with n-butyl substituent. Two of the most cytotoxic analogs were then selected for further investigation on the HL-60 cell line. Both analogs induced morphological changes characteristic of apoptosis in cancer cells, significantly inhibited proliferation and induced apoptotic cell death. Both compounds also generated DNA damage, and one of the analogs arrested the cell cycle of HL-60 cells in the G2/M phase. In addition, both analogs were able to inhibit the activity of topoisomerase IIα. Based on these findings, the investigated analogs may be further optimized for the development of new and effective topoisomerase II inhibitors. 相似文献
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Tomasz A. Dziedzic Kacper Koczyk Arkadiusz Nowak Edyta Maj Andrzej Marchel 《Journal of Korean Neurosurgical Society》2022,65(3):415
ObjectiveSeizure recurrence after the first-ever seizure in patients with a supratentorial cerebral cavernous malformation (CCM) is almost certain, so the diagnosis and treatment of epilepsy is justified. The optimal method of management of these patients is still a matter of debate. The aim of our study was to identify factors associated with postoperative seizure control and assess the surgical morbidity rate. MethodsWe retrospectively analysed 45 consecutive patients with a supratentorial CCM and symptomatic epilepsy in a single centre. Pre- and postoperative epidemiological data, seizure-related patient histories, neuroimaging results, surgery details and outcomes were obtained from hospital medical records. Seizure outcomes were assessed at least 12 months after surgery. ResultsThirty-five patients (77.8%) were seizure free at the long-term follow-up (Engel class I); six (13,3%) had rare, nocturnal seizures (Engel class II); and four (8.9%) showed meaningful improvement (Engel class III). In 15 patients (33%) in the Engel I group; it was possible to discontinue antiepileptic medication. Although there was not statistical significance, our results suggest that patients can benefit from early surgery. No deaths occurred in our study, and mild postoperative neurologic deficits were observed in two patients (4%) at the long-term follow-up. ConclusionSurgical resection of CCMs should be considered in all patients with a supratentorial malformation and epilepsy due to the favourable surgical results in terms of the epileptic seizure control rate and low postoperative morbidity risk, despite the use of different predictors for the seizure outcome. 相似文献
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Tomasz Jazwiec Marcin Malinowski Haley Ferguson Jeremy Wodarek Nathan Quay Jared Bush Matthew Goehler Jessica Parker Manuel Rausch Tomasz A. Timek 《The Journal of thoracic and cardiovascular surgery》2021,161(4):e277-e286
ObjectiveTo investigate the effect of variable tricuspid annular reduction (TAR) on functional tricuspid regurgitation (FTR) and right ventricular (RV) dynamics in ovine tachycardia-induced cardiomyopathy.MethodsNine adult sheep underwent implantation of a pacemaker with an epicardial lead and were paced at 200 to 240 bpm until the development of biventricular dysfunction and functional TR was noted. During reoperation on cardiopulmonary bypass, 6 sonomicrometry crystals were placed around the tricuspid annulus (TA) and 14 were placed on the RV epicardium. Annuloplasty suture was placed around the TA and externalized to an epicardial tourniquet. After weaning from cardiopulmonary bypass, echocardiographic, hemodynamic, and sonomicrometry data were acquired at baseline and during 5 progressive TARs achieved with suture cinching. TA area and RV free wall strains and function were calculated from crystal coordinates.ResultsAfter pacing, changes in left ventricular (LV) ejection fraction and RV fractional area decreased significantly. Mean TA diameter increased from 25.1 ± 2.9 mm to 31.5 ± 3.3 mm (P = .005), and median TR (range, 0-3+) increased from 0 (0) to 3 (2) (P = .004). Progressive suture cinching reduced the TA area by 18 ± 6%, 38 ± 11%, 56 ± 10%, 67 ± 9%, and 76 ± 8%. Only aggressive annular reductions (67% and 76%) decreased TR significantly, but these were associated with deterioration of RV function and strain. A moderate annular reduction of 56% led to a substantial reduction of TR with little deleterious effect on regional RV function.ConclusionsA moderate TAR of approximately 50% may be most advantageous for correction of functional TR and simultaneous maintenance of regional RV performance. Additional subvalvular interventions may be needed to achieve complete valvular competence. 相似文献
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Eleonora Mess Magdalena Witkowicz Maciej Ornat Piotr Sielski Tomasz Klaszczyk 《Archives of Psychiatric Nursing》2018,32(5):688-694
The objective of the study was to assess the severity of depression and to assess the level of self-sufficiency of patients with Alzheimer's disease, with particular emphasis on the place of residence and level of education. The study covered 90 people diagnosed with Alzheimer's disease. All respondents were persons over 65?years of age and residents of cities with a population over one-hundred thousand. The research method based on this work is the author's own questionnaire, the Zung Self-Rating Depression Scale (ZSDS) about depression and the Karnofsky Performance Scale Index (KPSI) for assessment of a patient's self-sufficiency. Regardless of residence, patients with Alzheimer's disease displayed signs of mild or moderate depression (100% in social welfare homes and hospital patients and 60% in those with caregivers at home). Patients with Alzheimer's disease have an unsatisfactory salary in social-economic terms. In those with Alzheimer's disease, quality of life is best for those in family homes under the care of their immediate family. People with a vocational education were the largest group of people diagnosed with Alzheimer's. Patients at home and in the hospital had a higher level of physical activity, but most patients in the hospital needed regular medical care, as did patients in social welfare homes. 相似文献
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Rakowski Tomasz Siudak Zbigniew Dziewierz Artur Plens Krzysztof Kleczyński Paweł Dudek Dariusz 《Journal of thrombosis and thrombolysis》2018,45(1):151-157
Journal of Thrombosis and Thrombolysis - According to guidelines, it is recommended to give P2Y12 inhibitors (preferably ticagrelor or prasugrel) at the time of first medical contact in patients... 相似文献