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排序方式: 共有316条查询结果,搜索用时 15 毫秒
1.
Devika Soundara Manickam Harender S Bisht Lei Wan Guangzhao Mao David Oupicky 《Journal of controlled release》2005,102(1):293-306
Use of bioactive cationic peptides as gene carriers is limited by instability of their DNA complexes in vivo and by the loss of their biological activity due to undesired interactions of their bioactive parts with the DNA. To overcome the two major limitations, biodegradable high-molecular-weight form of TAT peptide (POLYTAT) sensitive to cellular redox-potential gradients was synthesized in this study by oxidative polycondensation. Physicochemical and transfection properties of DNA polyplexes based on POLYTAT were investigated and compared with polyplexes based on TAT polymer prepared by in situ template-assisted polymerization. Physicochemical properties of TAT-based polyplexes were affected by the molecular weight and method of polymerization of the TAT peptide. All TAT-based DNA polyplexes exhibited reduced cytotoxicity when compared with control polyethylenimine (PEI) polyplexes. Polyplexes based on both high-molecular-weight TAT polypeptides exhibited increased transfection efficiency compared to control TAT peptide but lower than that of PEI polyplexes. The evidence shows that transfection activity of TAT-based polyplexes is strongly dependent on the presence of chloroquine and therefore suggests that TAT polyplexes are internalized by an endocytosis. Overall, high-molecular-weight reducible polycations based on bioactive peptides has the potential as versatile carriers of nucleic acids that display low cytotoxicity and can prove to be especially beneficial in cases that require surface presentation of membrane-active or cell-specific targeting peptides. 相似文献
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Activity of telithromycin against key pathogens associated with community-acquired respiratory tract infections 总被引:3,自引:0,他引:3
OBJECTIVES: To investigate the correlation between in vitro susceptibility of isolates and clinical outcomes with telithromycin in respiratory tract infections. METHODS: The activity of telithromycin was determined by in vitro susceptibility testing of key respiratory tract pathogens isolated from patients with community-acquired pneumonia, acute exacerbations of chronic bronchitis or acute maxillary sinusitis enrolled in 14 Phase III/IV clinical trials evaluating the clinical efficacy of telithromycin. RESULTS: In this pooled analysis, telithromycin mode minimum inhibitory concentration (MIC) and MIC90, respectively, were: 0.016 and 0.03 mg/l against Streptococcus pneumoniae (n=626); 0.03 and 0.5 mg/l for penicillin-resistant S. pneumoniae (n=56); 0.03 and 1 mg/l for erythromycin-resistant S. pneumoniae (n=81); 2 and 4 mg/l against Haemophilus influenzae (including beta-lactamase producers; n=627); both 0.12 mg/l for Moraxella catarrhalis (n=159) and both 0.25 mg/l for Staphylococcus aureus (n=124). Telithromycin (5 or 7-10 days) resulted in overall clinical and bacteriologic success rates of 88.1% (1593/1808) and 89% (1593/1789), respectively. CONCLUSIONS: High levels of in vitro susceptibility to telithromycin are paralleled by high rates of clinical cure and bacteriologic eradication. 相似文献
3.
Chhibber-Goel Jyoti Singhal Varsha Gaur Anamika Yogavel Manickam Sharma Amit 《Proceedings of the National Academy of Sciences, India. Section B.》2018,88(4):1681-1690
Proceedings of the National Academy of Sciences, India Section B: Biological Sciences - Mutations in human flavin monooxygenase-3 (hFMO3) enzyme have been implicated in the rare autosomal recessive... 相似文献
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Humeral shaft fractures account for 1–3% of all fractures. Non-surgical management with functional bracing is arguably the standard of care for most humeral shaft fractures.It results in high union rates and in general the outcome is excellent. Surgical management is indicated in some cases, such as open fractures, polytrauma, those with associated vascular injury, pathological fractures, floating elbow injuries and fractures that have failed non-surgical management. Options for surgical fixation include open reduction and internal fixation with plate osteosynthesis, antegrade or retrograde intramedullary nailing and external fixation. Both plate osteosynthesis and intramedullary nailing yield similar results, with a slightly higher rate of complications and re-operations with nailing. A high incidence of radial nerve injury has been associated with humeral shaft fractures and should be actively sought. The management of nerve injuries is still a matter of debate, however; initial expectant treatment with delayed exploration if needed seems to yield similar results to early exploration. Proper patient selection is key to achieving good outcomes with both surgical and non-surgical management of these injuries. 相似文献
7.
Martin?L.?GunnEmail author Jennifer?R.?Marin Angela?M.?Mills Suzanne?T.?Chong Adam?T.?Froemming Jamlik?O.?Johnson Manickam?Kumaravel Aaron?D.?Sodickson 《Emergency radiology》2016,23(4):383-396
In May 2015, the Academic Emergency Medicine consensus conference “Diagnostic imaging in the emergency department: a research agenda to optimize utilization” was held. The goal of the conference was to develop a high-priority research agenda regarding emergency diagnostic imaging on which to base future research. In addition to representatives from the Society of Academic Emergency Medicine, the multidisciplinary conference included members of several radiology organizations: American Society for Emergency Radiology, Radiological Society of North America, the American College of Radiology, and the American Association of Physicists in Medicine. The specific aims of the conference were to (1) understand the current state of evidence regarding emergency department (ED) diagnostic imaging utilization and identify key opportunities, limitations, and gaps in knowledge; (2) develop a consensus-driven research agenda emphasizing priorities and opportunities for research in ED diagnostic imaging; and (3) explore specific funding mechanisms available to facilitate research in ED diagnostic imaging. Through a multistep consensus process, participants developed targeted research questions for future research in six content areas within emergency diagnostic imaging: clinical decision rules; use of administrative data; patient-centered outcomes research; training, education, and competency; knowledge translation and barriers to imaging optimization; and comparative effectiveness research in alternatives to traditional computed tomography use. 相似文献
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Manickam Ramalingam Anandan Murugesan Kallappan Senthil Mizar Ganapathy Pai 《JSLS, Journal of the Society of Laparoendoscopic Surgeons》2014,18(2):294-300
Background:
Laparoscopic pyeloplasty is one of the most common reconstructive procedures performed by urologists. Both continuous and interrupted sutures are being practiced for ureteropelvic anastomosis. The success rate and the complications associated with the suturing technique needs evaluation. We analyzed the results from of our patients who underwent laparoscopic pyeloplasty using both techniques.Objective:
To review the outcome differences among patients undergoing laparoscopic pyeloplasty regarding suturing technique.Materials and Methods:
All patients who underwent laparoscopic, transperitoneal dismembered pyeloplasty of the primary pelviureteric obstruction were analyzed. The primary outcome was successful pyeloplasty, as assessed by the resolution of symptoms and T½ <10 minutes. The secondary outcomes were the complication rate and the operative parameters. The difference in the parameters was assessed by Student t test analysis.Results:
Of the 107 patients we studied, 65 had interrupted suturing and 42 had continuous suturing. The success rate was not significantly different among the 2 groups. The mean suturing time, postoperative drainage volume, postoperative hospital stay, and total cost of the procedure were significantly less in the continuous suturing group.Conclusion:
The continuous suturing technique is preferred over the interrupted suturing technique for laparoscopic pyeloplasty because the success rates are equal and the postoperative stay, suturing time, drain output, and cost of the procedure are better. 相似文献10.
Manickam Bakthadoss Jayakumar Srinivasan Mir Ashiq Hussain Duddu S. Sharada 《RSC advances》2019,9(42):24314
A new one pot assembly of highly functionalized benzo[a]phenazinone fused chromene/bicyclic scaffolds via a domino Knoevenagel intramolecular hetero-Diels–Alder (IMHDA) strategy using a solid state melt reaction (SSMR) of 2-hydroxynaphthalene 1,4-dione, o-phenylenediamine, O-allyl salicylaldehyde/O-vinyl salicylaldehyde derivatives is reported. The formation of five new bonds (two C–C bonds and three C–O bonds), three six-membered rings, and three stereogenic centers in a one-pot manner is very attractive. Ease of reaction with short time, good yields with water as the only byproduct and work up free procedure are some of the excellent features of the present protocol.A new one pot assembly of highly functionalized benzo[a]phenazinone fused chromene/bicyclic scaffolds via a domino Knoevenagel intramolecular hetero-Diels–Alder (IMHDA) strategy using a solid state melt reaction (SSMR) is reported.Multicomponent reactions (MCRs)1 are known to construct complex structures from simple starting materials in a rapid and highly efficient manner where the production of wastes is minimized. Those multicomponent reactions which are carried out in a ‘one-pot’ MC sequential manner provide a high degree of reaction mass efficiency, which is crucial in the development of modern synthetic methodology for drug discovery and pharmaceutical programs.2 Enormous work has been carried out in the field of multicomponent reactions in the past decade where several MCRs have been developed and extensively used in natural product synthesis and drug discovery. The Ugi reaction is a prime example of a four-component reaction that has been found to be a powerful and efficient method for the preparation of α-amino amides both in academia and industry.3 Therefore, the development of new MCRs for the synthesis of biologically active molecules continues to attract considerable attention for their atom- and step economy features.Heterocycles having nitrogen atom are widely available in nature and possess diverse and important biological activities.4 Phenazines are a group of organic compounds known to the mankind since past 150 years and are known to exhibit significant biological activities such as antimalarial, fungicidal, trypanocidal, antiplatelet, etc.5 A large number of drug molecules bearing the phenazine scaffold have been designed and evaluated in the recent years. The phenazines motif possess two dentate N atoms with three fused aromatic rings and an electron deficient conjugated system. The presence of the above features in phenazines give them an ability to form hydrogen bonds, ionic bonds, and π–π interactions with relative ease, and their use has also been demonstrated in supramolecular chemistry for molecular recognition (MR), supramolecular self-assembly (MS-A), and organic optic electronics materials.6 Few representative examples of phenazine and its derivatives are shown in the Fig. 1.Open in a separate windowFig. 1Some of naturally occurring phenazine derivatives.Chromenes and their derivatives are privileged scaffolds due to their ubiquitous presence in many natural products and synthetic molecules.7 Chromenes are also an important class of compounds displaying interesting biological activities against prostate cancer (DU-145) and breast cancer (MCF-7).8 Additionally, they have medicinal qualities such as antiviral and antimicrobial activity.9 Chromenes have also found their use in medicine, health-promoting agents, and photochromic materials.10In recent years, the domino-Knoevenagel-hetero-Diels–Alder reaction (DKHDA) which was extensively studied by Tietze''s group constitutes an important process for the preparation of complex compounds having interesting biological properties.11 The Diels–Alder reaction is important since it allows the formation of functionalized rings where there is complete control on regio-, diastereo-, and enantioselectivity. Moreover, the concerted nature of the Diels–Alder reactions allow the selective formation of up to three stereogenic centers in a single reaction step. Majority of the reactions reported on DKHDA have utilized 1,3-dicarbonyl compounds such as dimethyl barbituric acid, Meldrum''s acid and 1,3-indanedione.12 Additionally, other active methylene compounds like 1-phenyl-3-methyl pyrazolone, 4-hydroxy-coumarin, dihydroindole-2-thione, benzoylacetonitrile, 4-hydroxydithiocoumarin have been also used;13 but phenazinones have never been employed in DKHDA reactions. To the best of our knowledge, there are no reports on intramolecular DKHDA reactions using phenazinone as the coupling partner. Due to our interest in the construction of bioactive fused chromenophenazinone derivatives and since this molecule contains a 1,3-dicarbonyl as well as a 1,3-imine moiety, it would be very challenging to control the regioselectivity of the molecule; therefore phenazinone scaffold can act as a model substrate for an intramolecular DKHDA. We envisaged that a series of angular polycyclic chromeno fused phenazinone derivatives could be obtained and it is possible that the final hybrid compounds will result in being more selective and efficient than chromene and phenazinone compounds in biological assays.In this direction, we have decided to develop a new method for the preparation of novel benzo[a]phenazinone fused chromene/bicyclic scaffolds via a domino Knoevenagel intramolecular hetero-Diels–Alder (IMHDA) strategy using a solid state melt reaction (SSMR). As part of our research program for the development of new synthetic methods in heterocyclic chemistry14 and solid state melt reactions,15,16 we would like to report a simple and a general domino three-component reaction of 2-hydroxynaphthalene-1,4-dione, o-phenylenediamine and O-allylated/vinylated salicylaldehyde for the synthesis of pentacyclic benzo[a]phenazinone fused chromene/bicyclic scaffolds under environmentally benign reaction conditions (Scheme 1).Open in a separate windowScheme 1Synthetic approach to benzo[a]phenazinone fused chromenes.We have started this study by melting 2-hydroxynaphthalene-1,4-dione (2), o-phenylenediamine (1), and (E)-methyl 2-((2-formylphenoxy)methyl)-3-phenylacrylate (3) at 180 °C for 1 h in solvent free condition. Unfortunately, we could not obtain any desired product and the formation of a complex mixture was observed. To minimize the formation of the side products, the 2-hydroxynaphthalene-1,4-dione (2) and o-phenylenediamine (1) were first melted at 180 °C for 10 minutes to form the intermediate benzo[a]phenazin-5-ol. Subsequently, (E)-methyl 2-((2-formylphenoxy)methyl)-3-phenylacrylate 3a was added and the mixture was melted under the same temperature for 1 h which afforded the desired hybrid product chromene fused benzo[a]phenazinone 4a (ester moiety in ring junction) in 78% yield as shown in