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5-(2-Acylethynyl)-2,4-dimethoxypyrimidines (3-6) were synthesized in excellent yields from 2,4-dimethoxy-5-[2-(trimethylsilyl)ethynyl]pyrimidine (2) by treatment with acid chlorides in the presence of anhydrous aluminum chloride. Compounds 3-6 were deblocked with chlorotrimethylsilane and sodium iodide in acetonitrile to the corresponding 5-[(2-acyl-1-iodo)vinyl]uracils (7-10), which on treatment with potassium hydroxide in dioxane yielded the corresponding 5-(2-acylethynyl)uracils (11-14). The 5-(2-acylethynyl)uracils were found to be active against Ehrlich ascites carcinoma (EAC) cells in vivo, the most active compounds being 5-(2-benzoylethynyl)uracil (11) and 5-(2-p-toluoylethynyl)uracil (12). The T/C values of 281 and 300 were obtained for compounds 11 and 12, respectively, in the case of mice bearing EAC cells. The 5-(2-acylethynyl)uracils have also shown in vitro activity against CCRF-CEM and L1210/0 tumor cell lines. The lead compound 5-(2-p-toluoylethynyl)uracil effectively inhibited thymidylate synthetase. 相似文献
3.
Endothelin-1 (ET-1) is a potent, vasoconstrictive peptide isolated from culture media of vascular endothelial cells. The binding of ET-1 to membrane preparations from rat and bovine lung was studied using radioiodinated ET-1 (125I-ET-1). With both membrane preparations, 125I-ET-1 showed saturable binding to a single class of high affinity sites. Scatchard analysis of the binding data gave dissociation constants (Kd) for ET-1 of 0.22 nM and 0.15 nM, and receptor densities (Bmax) of 6.1 pmol/mg and 2.7 pmol/mg for rat and bovine lung membranes, respectively. Photo-reactive radioiodinated ET-1, N epsilon 9-azidobenzoyl-125I-ET-1, was synthesized and purified as a mono-reactive affinity labeling reagent. This reagent was used for affinity labeling of ET-1 receptor in bovine and rat lung membranes. Photoaffinity labeling followed by sodium dodecyl sulfate gel electrophoresis and autoradiography gave a radiolabeled protein band with an apparent Mr of 34,000 in both membrane preparations. The labeling of this protein band was inhibited by cold ET-1 in a concentration-dependent manner. Labeling was not abolished by unrelated peptides such as angiotensin II and [Arg8]-vasopressin, or by structurally related bee venom apamin. These results indicate that the ET-1 receptor or its ligand binding subunit consists of a 34,000 Da polypeptide. 相似文献
4.
The propagation speed (C) of surface acoustic waves (SAW), e.g. Rayleigh (R-waves) and longitudinal lateral waves (L-waves), the latter being the surface manifestation of the longitudinal waves, strongly reflect mechanical properties of materials. In view of an increasing interest in ultrasonic methodology in the field of bone biomechanics, we tested the hypothesis that both R- and L-waves can be excited in trabecular bone using an acoustic microscope at 1 GHz and that their speeds (C(R) and C(L)) can be extracted from V(z)-curves, i.e. plots of lens output voltage as a function of the lens focal point position with respect to the specimen surface. In accordance with V(z)-curves theoretically synthesized on the basis of incident field theory, experimental curves for canine femoral trabecular bone showed evidence of both R- and L-waves in almost all regions of recording. The measured CR ranged between 1.93 and 2.07 km/s (mean +/- SD.: 2.00=0.06 km/s) and the C(L) ranged between 2.33 and 4.33 km/s (3.37+/-0.61 km/s). Knowledge of both speeds allowed computation of a number of material constants by means of simple theory of elasticity and assumptions of the material density. We found values of Poisson ratio (v) ranging from 0.14 to 0.32 (0.23+/-0.07). Young's modulus (E) from 15 to 22.8 GPa (19.9+/-2.5 GPa) and the shear modulus (G) from 7.6 to 8.9 GPa (8.4+/-0.5 GPa). Anisotropy in the trabecular bone material was clearly detected at the micrometer level. In conclusion, the V(z)-curve method was successfully used to determine the distribution of material elastic constants of trabecular bone with micrometer resolution. 相似文献
5.
Singh P Mathur SK Kundu ZS Singh S Marwah N Arora B 《Indian journal of pathology & microbiology》2005,48(2):206-208
Extraskeletal chondroma is a rare entity. A fairly benign condition, it is usually seen in adults. It presents as an enlarging mass, most commonly in the hand. Local excision is the treatment of choice. We present a case of extraskeletal chondroma of hand in a 12 year male child. Its variable histological appearance not infrequently leads to a mistaken diagnosis of chondrosarcoma. 相似文献
6.
Detection of beet yellows virus by RT-PCR and immunocapture RT-PCR in Tetragonia expansa and Beta vulgaris 总被引:1,自引:0,他引:1
Two sensitive methods, RT-PCR with phenol-extracted RNA or Triton X-100-released RNA and immunocapture RT-PCR (IR-RT-PCR) were used for the detection of Beet yellows virus (BYV) in young and old leaves of Tetragonia expansa and sugar beet (Beta vulgaris) and in sugar beet roots. Four oligonucleotide primer pairs proved suitable for the detection of BYV. The release of BYV RNA with Triton X-100 was shown to be a very effective and easy as compared to isolation of total RNA by phenol extraction with the same or higher sensitivity of subsequent PCR. Using the Triton X-100 release of RNA and IC-RT-PCR the sensitivity of detection was so high that pg amounts of BYV RNA occurring in dilutions up to 10(-6) of saps from young Tetragonia and sugar beet leaves could be detected. 相似文献
7.
Kundu Abhishake Feijoo Felipe Martinez Diego A. Hermosilla Manuel Matis Timothy 《Health care management science》2022,25(1):89-99
Health Care Management Science - Proactive and objective regulatory risk management of ongoing clinical trials is limited, especially when it involves the safety of the trial. We seek to... 相似文献
8.
Rheumatic heart disease is a significant clinical entity in young children, especially in the developing world. One of the major long-term effects of ill managed rheumatic fever is irreversible damage to the cardiac valve leaflets, primarily on the left side. With the limited success of currently available mechanical and bioprosthetic valves, there is an urgent need for new directions in bioprosthetic valves, both in material, including source, degree of fixation, surface, bulk modifications, etc., and design. In the present paper, new proposals in the material selection and fabrication of bioprosthetic valves are proposed based on electron microscopic studies of natural valve leaflets and the pericardial surface. Current approaches for bioprosthetic valve fabrications include the wide use of the pericardium as a leaflet material. The present study indicates a need for nondestructive surface examination of pericardial sheets for the elimination of areas of surface voids resulting from gross fiber disorientation. Also, there seems to be a need for incorporation of an in situ fiber renewal mechanism in bioprosthetic leaflets to emulate the natural valve more closely. Apparently natural leaflets have built-in fiber renewal mechanism(s). 相似文献
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10.
Panchanan Sahoo Sudip Kundu Shubham Roy S. K. Sharma Jiten Ghosh Snehasis Mishra Abhishek Mukherjee Chandan Kumar Ghosh 《RSC advances》2022,12(38):24555
A targeted multimodal strategy on a single nanoplatform is attractive in the field of nanotheranostics for the complete ablation of cancer. Herein, we have designed mesoporous silica (m-SiO2)-coated Prussian blue nanocubes (PBNCs), functionalized with hyaluronic acid (HA) to construct a multifunctional PBNC@m-SiO2@HA nanoplatform that exhibited good biocompatibility, excellent photodynamic activity, and in vitro T1-weighted magnetic resonance imaging ability (r1 ∼ 3.91 mM−1 s−1). After loading doxorubicin into the as-prepared PBNC@m-SiO2@HA, the developed PBNC@m-SiO2@HA@DOX displayed excellent pH-responsive drug release characteristics. Upon irradiation with 808 nm (1.0 W cm−2) laser light, PBNC@m-SiO2@HA@DOX exhibited synergistic photodynamic and chemotherapeutic efficacy (∼78% in 20 minutes) for human colorectal carcinoma (HCT 116) cell line compared to solo photodynamic or chemotherapy. Herein, the chemo-photodynamic therapeutic process was found to follow the apoptotic pathway via ROS-mediated mitochondrion-dependent DNA damage with a very low cellular uptake of PBNC@m-SiO2@HA@DOX for the human embryonic kidney (HEK 293) cell line, illustrating its safety. Hence, it may be stated that the developed nanoplatform can be a potential theranostic agent for future applications. Most interestingly, we have noted variation in r1 at each step of the functionalization along with size variation that has been the first time modelled on the basis of the Solomon–Bloembergen–Morgan theory considering changes in the defect crystal structure, correlation time, water diffusion rate, etc., due to varied interactions between PBNC and water molecules.A targeted multimodal strategy on a single nanoplatform is attractive in the field of nanotheranostics for the complete ablation of cancer. 相似文献