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31.
Gautam Kumar Vagolu Siva Krishna Dharmarajan Sriram Sanjay M. Jachak 《Archiv der Pharmazie》2020,353(8):2000077
Pyrazole, coumarin, and quinoline are medicinally important moieties. In this study, two series of novel pyrazole–coumarin chalcones and pyrazole–quinoline chalcones were synthesized using multiple-step reactions. All the synthesized compounds were well characterized using different spectroscopic techniques including 1H and 13C nuclear magnetic resonance, high-resolution mass spectroscopy, and electrospray ionization–mass spectrometry. The compounds were evaluated for their antitubercular activity against the Mycobacterium tuberculosis H37Rv strain using the microplate Alamar Blue assay, and the minimal inhibitory concentrations (MIC) of the compounds were determined. Among the 32 tested compounds, compounds 3e , 3u , and 7h showed an MIC value of 3.125 µg/ml, and they were found to be nontoxic. Molecular docking studies of the compounds with the enzyme DprE1 revealed the probable mechanism of action. The chalcone derivatives exhibited binding affinity values between −7.047 and −9.353 kcal/mol. ADME parameters were predicted using the QikProp module of the Schrödinger software, and these compounds exhibited good pharmacological and oral absorption properties. 相似文献
32.
Interaction between sleep and the immune response in Drosophila: a role for the NFkappaB relish 总被引:1,自引:0,他引:1
STUDY OBJECTIVES: The regulation of sleep is poorly understood. While some molecules, including those involved in inflammatory/immune responses, have been implicated in the control of sleep, their role in this process remains unclear. The Drosophila model for sleep provides a powerful system to identify and test the role of sleep-relevant molecules. DESIGN: We conducted an unbiased screen for molecular candidates involved in sleep regulation by analyzing genome-wide changes in gene expression associated with sleep deprivation in Drosophila. To further examine a role of immune-related genes identified in the screen, we performed molecular assays, analysis of sleep behavior in relevant mutant and transgenic flies, and quantitative analysis of the immune response following sleep deprivation. RESULTS: A major class of genes that increased expression with sleep deprivation was that involved in the immune response. We found that immune genes were also upregulated during baseline conditions in the cyc01 sleep mutant. Since the expression of an NFkappaB, Relish, a central player in the inflammatory response, was increased with all manipulations that reduced sleep, we focused on this gene. Flies deficient in, but not lacking, Relish expression exhibited reduced levels of nighttime sleep, supporting a role for Relish in the control of sleep. This mutant phenotype was rescued by expression of a Relish transgene in fat bodies, which are the major site of inflammatory responses in Drosophila. Finally, sleep deprivation also affected the immune response, such that flies deprived of sleep for several hours were more resistant to bacterial infection than those flies not deprived of sleep. CONCLUSION: These results demonstrate a conserved interaction between sleep and the immune system. Genetic manipulation of an immune component alters sleep, and likewise, acute sleep deprivation alters the immune response. 相似文献
33.
Alex Bottle Chiara Maria Ventura Kumar Dharmarajan Paul Aylin Francesca Ieva Anna Maria Paganoni 《Health care management science》2018,21(2):292-304
Heart failure (HF) is a common, serious chronic condition with high morbidity, hospitalisation and mortality. The healthcare systems of England and the northern Italian region of Lombardy share important similarities and have comprehensive hospital administrative databases linked to the death register. We used them to compare admission for HF and mortality for patients between 2006 and 2012 (n = 37,185 for Lombardy, 234,719 for England) with multistate models. Despite close similarities in age, sex and common comorbidities of the two sets of patients, in Lombardy, HF admissions were longer and more frequent per patient than in England, but short- and medium-term mortality was much lower. English patients had more very short stays, but their very elderly also had longer stays than their Lombardy counterparts. Using a three-state model, the predicted total time spent in hospital showed large differences between the countries: women in England spent an average of 24 days if aged 65 at first admission and 19 days if aged 85; in Lombardy these figures were 68 and 27 days respectively. Eight-state models suggested disease progression that appeared similar in each country. Differences by region within England were modest, with London patients spending more time in hospital and having lower mortality than the rest of England. Whilst clinical practice differences plausibly explain these patterns, we cannot confidently disentangle the impact of alternatives such as coding, casemix, and the availability and use of non-hospital settings. We need to better understand the links between rehospitalisation frequency and mortality. 相似文献
34.
Prabu Baskaran Rengaraj Venkatesh Seema Ramakrishnan Ravilla Duraisami Sriram Gautham Iyer R K Ramnath 《Indian journal of ophthalmology》2020,68(10):2205
The aim of this study was to describe a novel device that has been designed to facilitate anterior segment and novice surgeons to perform extraocular needle-guided haptic insertion technique (X-NIT) for scleral fixation intraocular lens surgery (SFIOL). We performed SFIOL surgery using X-NIT device in 21 eyes of 21 patients. The mean preoperative best-corrected visual acuity (BCVA) was 0.5 ± 0.2 logarithm of minimum angle of resolution (log MAR), which improved by one or more lines postoperatively in all eyes. There were no intraoperative complications. Postoperatively, we noted minimal corneal edema in one patient and dispersed vitreous hemorrhage in one patient. The sharpness and angulation of the needle and the haptic holding ability of silicone stopper were found to be satisfactory. The X-NIT device may potentially improve the safety of SFIOL procedures by minimizing intraocular maneuvers. 相似文献
35.
Sumitha Muthu Jitendra Jethani Sriram Annavajjhala Sneha Gupta Krati Gupta Pooja Khamar 《Indian journal of ophthalmology》2020,68(12):2835
Refractive surgeries are one of most commonly performed surgeries for correcting visual impairment due to refractive errors. With the increase in demand for refractive surgeries, there is an enormous strain on the operating surgeon for delivering ideal outcomes i.e 20/20 visual acuity. Regression, under-correction and ectasia are the most dreaded complications post-refractive correction, for the surgeon as well as the patient. They have significant effects on the quantity of the vision and most importantly on the quality of life of the patient. With the advent of digital era and jobs requiring the eyes being glued to the screen for hours there has been a surge in the patients presenting with complaints of asthenopia, glare, halos, and difficulty in focusing; pointing towards diagnosis of non-strabismic binocular vision anomalies (NSBVA). NSBVA in a postrefractive surgery patient may masquerade as regression or under-correction. However, timely diagnosis of NSBVA in such patients would prevent the greater harm caused by wrongful re-correction. Home- and office-based vision therapy results in improvement in visual acuity in a large majority of these patients. This preferred practice pattern intends to guide the refractive surgeons to diagnose and treat the postrefractive surgery NSBVA following a case-based and algorithmic approach. It also emphasizes the inclusion of the binocular vision assessment as a part of the pre-operative workup for patients undergoing refractive procedures. 相似文献
36.
37.
Sriramoju Bharath Kumar Mettu Ravinder Golla Kishore Vaidya Jayathirtha Rao Perumal Yogeeswari Darmarajan Sriram 《Medicinal chemistry research》2014,23(4):1934-1940
Baylis–Hillman adduct-derived N-cinnamyl-substituted isatin derivatives were synthesized and evaluated for their antitubercular activity on Mycobacterium tuberculosis H37Rv strain ATCC 27294 by agar dilution method. Anticancer activity for the same compounds was also screened on four different cell lines: Chinese hamster ovary (CHO cells), Colo 205 (human colon cancer), Sup-T1 (human lymphoma) and C6 glioma (rat glioma) by MTT assay method. The compounds (3j–l) have shown significant activity against Mycobacterium strain and the compound 3l has shown specific cytotoxic activity. 相似文献
38.
39.
Electron diffraction studies of light-induced conformational changes in the Leu-93 → Ala bacteriorhodopsin mutant 下载免费PDF全文
Sriram Subramaniam A. R. Faruqi Dieter Oesterhelt Richard Henderson 《Proceedings of the National Academy of Sciences of the United States of America》1997,94(5):1767-1772
We previously have presented evidence for prominent structural changes in helices F and G of bacteriorhodopsin during the photocycle. These changes were determined by carrying out electron diffraction analysis of illuminated two-dimensional crystals of wild-type bacteriorhodopsin or the Asp-96 → Gly mutant that were trapped at a stage in the photocycle after light-driven proton release, but preceding proton uptake from the aqueous medium. Here, we report structural analysis of the long-lived O intermediate observed in the photocycle of the Leu-93 → Ala mutant, which accumulates after the release and uptake of protons, but before the reisomerization of retinal to its initial all-trans state. Projection Fourier difference maps show that upon illumination of the Leu-93 → Ala mutant, significant structural changes occur in the vicinity of helices C, B, and G, and to a lesser extent near helix F. Our results suggest that (i) all four helices that line the proton channel (B, C, F, and G) participate in structural changes during the late stages of the photocycle, and (ii) completion of the photocycle involves significant conformational changes in addition to those that are associated with steps in proton transport. 相似文献
40.
Suveen Angraal Rohan Khera Shengfan Zhou Yongfei Wang Zhenqiu Lin Kumar Dharmarajan Nihar R. Desai Susannah M. Bernheim Elizabeth E. Drye Khurram Nasir Leora I. Horwitz Harlan M. Krumholz 《The American journal of medicine》2018,131(11):1324-1331.e14