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排序方式: 共有114条查询结果,搜索用时 15 毫秒
81.
Raksha Dhankar Anjali M. Rahatgaonkar Rakesh Shukla Mukund Chorghade Ashutosh Tiwari 《Medicinal chemistry research》2013,22(5):2493-2504
Simulation of virtually designed 20 compounds as COX-2 inhibitors using molecular modelling of protein–ligand interactions to predict drug structure–activity relationship was performed in this study. A synthetic route with a rational chemical approach to (E)-2-oxo-(thio)-4-substituted phenyl-6-styryl-1,2,3,4-tetrahydro-pyrimidine-5-caboxylic acid was designed and demonstrated. A comparative analysis of antimetabolite drug and corresponding metabolites (virtually designed compounds) provided a better understanding of rational drug design. COX-1(pdb entry: 1eqg) and COX-2(pdb entry: 6cox) enzymes docked with novel ligands were evaluated for binding energies. Lead optimization was performed by computational simulation: methoxy-substituted analogues displayed the highest negative ligand–protein-binding energies. These results prompted us to evaluate in vivo anti-inflammatory activity by carrageenan-induced paw oedema test in rats at a dose of 100 mg/kg. Ibuprofen was administered as standard drug. Lead compounds having significant activity were tested for in vitro cyclooxygenase isoenzyme inhibition assay and found to be more selective towards COX-2 as indicated by COX-2 selective index. The objective of our research is to accept the challenge of discovery of new drug. To ensure the desired target specificity and potency, bioavailability and lack of toxicity, our approach stems out lead generation from virtual screening to their synthesis and ends up with biological assays. 相似文献
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83.
Feed-forward excitation of striatal neuron activity by frontal cortical activation of nitric oxide signaling in vivo 总被引:2,自引:0,他引:2
Ondracek JM Dec A Hoque KE Lim SA Rasouli G Indorkar RP Linardakis J Klika B Mukherji SJ Burnazi M Threlfell S Sammut S West AR 《The European journal of neuroscience》2008,27(7):1739-1754
The gaseous neurotransmitter nitric oxide plays an important role in the modulation of corticostriatal synaptic transmission. This study examined the impact of frontal cortex stimulation on striatal nitric oxide efflux and neuron activity in urethane-anesthetized rats using amperometric microsensor and single-unit extracellular recordings, respectively. Systemic administration of the neuronal nitric oxide synthase inhibitor 7-nitroindazole decreased spontaneous spike activity without affecting activity evoked by single-pulse stimulation of the ipsilateral cortex. Train (30 Hz) stimulation of the contralateral frontal cortex transiently increased nitric oxide efflux in a robust and reproducible manner. Evoked nitric oxide efflux was attenuated by systemic administration of 7-nitroindazole and the non-selective nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester. Train stimulation of the contralateral cortex, in a manner identical to that used to evoke nitric oxide efflux, had variable effects on spike activity assessed during the train stimulation trial, but induced a short-term depression of cortically evoked activity in the first post-train stimulation trial. Interestingly, 7-nitroindazole potently decreased cortically evoked activity recorded during the train stimulation trial. Moreover, the short-term depression of spike activity induced by train stimulation was enhanced following pretreatment with 7-nitroindazole and attenuated after systemic administration of the dopamine D2 receptor antagonist eticlopride. These results demonstrate that robust activation of frontal cortical afferents in the intact animal activates a powerful nitric oxide-mediated feed-forward excitation which partially offsets concurrent D2 receptor-mediated short-term inhibitory influences on striatal neuron activity. Thus, nitric oxide signaling is likely to play an important role in the integration of corticostriatal sensorimotor information in striatal networks. 相似文献
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85.
Hiral Desai Ramita Sood Raksha Shah Jyoti Cawda Haren Pandya 《Indian journal of dental research》2006,17(1):45-49
Desmoplastic Ameloblastoma is a rare variant of ameloblastoma. 90 cases of desmoplastic ameloblastoma have been reported so far in literature. We are presenting a rare case of desmoplastic ameloblastoma in the ramus region of mandible with regards to its clinical and radiographical viewpoints. Only one other case of desmoplastic ameloblastoma has been reported in the ramus region of mandible of the 90 cases that we have reviewed. Review of literature has revealed the tumour to most commonly occur in the 3rd to 5th decade of life with a high preponderance of Japanese males. The anterior region of either jaw was most commonly found to be affected. Radiological appearance was most commonly of a mixed radio-lucent/radio-opaque type with a high incidence of poorly defined borders. However our case differed from the reviewed cases as it was found to be a unilocular lesion with well defined borders. Histopathological findings of our case were consistent with the hisotpathological appearance of the reviewed cases and showed extensive stromal desmoplasia and small tumour nests of odontogenic epithelium scattered in stroma. 相似文献
86.
Michael A Kraut Barbara Cherry Jeffery A Pitcock Raksha Anand Juan Li Lindsey Vestal Victor W Henderson John Hart 《Cognitive and behavioral neurology》2007,20(1):62-67
BACKGROUND: Between 10% and 15% of patients with the amnestic variety of Mild Cognitive Impairment (MCI) convert to Alzheimer disease (AD) per year. OBJECTIVE: Characterize cognitive markers that may herald conversion from MCI to AD and directly assess semantic memory in patients meeting criteria for amnestic MCI. DESIGN: Thirty-five amnestic MCI patients and 121 healthy aging controls enrolled at an Alzheimer Disease Center received a battery of standard neuropsychologic tests, and the Semantic Object Retrieval Test (SORT), a test that we have developed for the assessment of semantic memory and subsequent name production, and that has been shown to be able to differentiate between normals and patients with AD. RESULTS: On the basis of normative data from the SORT, the MCI subjects could be divided into 2 groups: 10 patients (29%) with a significant semantic impairment (SI+) and 25 without a semantic memory deficit (SI-). There was a significant correlation between all SORT variables and performance on the Boston Naming Test. In this MCI population, significantly impaired SORT performance was associated with a relative decrease in performance on tests of frontal lobe functions, although disruption of thalamic-related processes cannot be excluded as an etiology for semantic memory impairment. CONCLUSIONS: The SORT is a specific test of semantic memory, and is a sensitive measure of semantic memory deficits in patients who otherwise meet criteria for amnestic MCI. Using this specific assessment tool, a significant number of MCI patients were found to have semantic memory deficits. As these patients may be early in the course of possible progression toward dementia, the SORT or other tests of semantic memory may provide important diagnostic or prognostic information in patients with MCI. 相似文献
87.
Deborah J Gow Kristin A Sauter Clare Pridans Lindsey Moffat Anuj Sehgal Ben M Stutchfield Sobia Raza Philippa M Beard Yi Ting Tsai Graeme Bainbridge Pamela L Boner Greg Fici David Garcia-Tapia Roger A Martin Theodore Oliphant John A Shelly Raksha Tiwari Thomas L Wilson Lee B Smith Neil A Mabbott David A Hume 《Molecular therapy》2014,22(9):1580-1592
We have produced an Fc conjugate of colony-stimulating factor (CSF) 1 with an
improved circulating half-life. CSF1-Fc retained its macrophage growth-promoting
activity, and did not induce proinflammatory cytokines in vitro.
Treatment with CSF1-Fc did not produce adverse effects in mice or pigs. The
impact of CSF1-Fc was examined using the Csf1r-enhanced green
fluorescent protein (EGFP) reporter gene in MacGreen mice. Administration of
CSF1-Fc to mice drove extensive infiltration of all tissues by
Csf1r-EGFP positive macrophages. The main consequence was
hepatosplenomegaly, associated with proliferation of hepatocytes. Expression
profiles of the liver indicated that infiltrating macrophages produced candidate
mediators of hepatocyte proliferation including urokinase, tumor necrosis
factor, and interleukin 6. CSF1-Fc also promoted osteoclastogenesis and produced
pleiotropic effects on other organ systems, notably the testis, where
CSF1-dependent macrophages have been implicated in homeostasis. However, it did
not affect other putative CSF1 targets, notably intestine, where Paneth cell
numbers and villus architecture were unchanged. CSF1 has therapeutic potential
in regenerative medicine in multiple organs. We suggest that the CSF1-Fc
conjugate retains this potential, and may permit daily delivery by injection
rather than continuous infusion required for the core molecule. 相似文献
88.
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90.
Kristina E. Hoque Raksha P. Indorkar Stephen Sammut Anthony R. West 《Psychopharmacology》2010,207(4):571-581