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Search Results: 1 - 10 of 130494 matches for " Dipti V Tillu "
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Resveratrol engages AMPK to attenuate ERK and mTOR signaling in sensory neurons and inhibits incision-induced acute and chronic pain
Dipti V Tillu, Ohannes K Melemedjian, Marina N Asiedu, Ning Qu, Milena De Felice, Gregory Dussor, Theodore J Price
Molecular Pain , 2012, DOI: 10.1186/1744-8069-8-5
Abstract: To test this hypothesis we used a potent and efficacious activator of AMPK, resveratrol. Our results demonstrate that resveratrol profoundly inhibits ERK and mTOR signaling in sensory neurons in a time- and concentration-dependent fashion and that these effects are mediated by AMPK activation and independent of sirtuin activity. Interleukin-6 (IL-6) is thought to play an important role in incision-induced pain and resveratrol potently inhibited IL-6-mediated signaling to ERK in sensory neurons and blocked IL-6-mediated allodynia in vivo through a local mechanism of action. Using a model of incision-induced allodynia in mice, we further demonstrate that local injection of resveratrol around the surgical wound strongly attenuates incision-induced allodynia. Intraplantar IL-6 injection and plantar incision induces persistent nociceptive sensitization to PGE2 injection into the affected paw after the resolution of allodynia to the initial stimulus. We further show that resveratrol treatment at the time of IL-6 injection or plantar incision completely blocks the development of persistent nociceptive sensitization consistent with the blockade of a transition to a chronic pain state by resveratrol treatment.These results highlight the importance of signaling to translation control in peripheral sensitization of nociceptors and provide further evidence for activation of AMPK as a novel treatment avenue for acute and chronic pain states.Incision associated with surgery causes acute pain and surgery has been identified as a potential major cause of chronic pain conditions [1-3]. Between 10 and 50% of patients develop chronic pain following surgical procedures such as groin hernia repair, breast and thoracic surgery, leg amputation, or coronary artery bypass surgery [2]. Despite improvements in post-surgical pain treatment strategies, the incidence of moderate to severe pain after surgery is still high in several patient populations [4,5]. Moreover, the exact mechanisms involv
Development and Evaluation of Small Peptidomimetic Ligands to Protease-Activated Receptor-2 (PAR2) through the Use of Lipid Tethering
Scott Boitano, Justin Hoffman, Dipti V. Tillu, Marina N. Asiedu, Zhenyu Zhang, Cara L. Sherwood, Yan Wang, Xinzhong Dong, Theodore J. Price, Josef Vagner
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0099140
Abstract: Protease-activated receptor-2 (PAR2) is a G-Protein Coupled Receptor (GPCR) activated by proteolytic cleavage to expose an attached, tethered ligand (SLIGRL). We evaluated the ability for lipid-tethered-peptidomimetics to activate PAR2 with in vitro physiological and Ca2+ signaling assays to determine minimal components necessary for potent, specific and full PAR2 activation. A known PAR2 activating compound containing a hexadecyl (Hdc) lipid via three polyethylene glycol (PEG) linkers (2at-LIGRL-PEG3-Hdc) provided a potent agonist starting point (physiological EC50 = 1.4 nM; 95% CI: 1.2–2.3 nM). In a set of truncated analogs, 2at-LIGR-PEG3-Hdc retained potency (EC50 = 2.1 nM; 1.3–3.4 nM) with improved selectivity for PAR2 over Mas1 related G-protein coupled receptor type C11, a GPCR that can be activated by the PAR2 peptide agonist, SLIGRL-NH2. 2at-LIG-PEG3-Hdc was the smallest full PAR2 agonist, albeit with a reduced EC50 (46 nM; 20–100 nM). 2at-LI-PEG3-Hdc retained specific activity for PAR2 with reduced EC50 (310 nM; 260–360 nM) but displayed partial PAR2 activation in both physiological and Ca2+ signaling assays. Further truncation (2at-L-PEG3-Hdc and 2at-PEG3-Hdc) eliminated in vitro activity. When used in vivo, full and partial PAR2 in vitro agonists evoked mechanical hypersensitivity at a 15 pmole dose while 2at-L-PEG3-Hdc lacked efficacy. Minimum peptidomimetic PAR2 agonists were developed with known heterocycle substitutes for Ser1 (isoxazole or aminothiazoyl) and cyclohexylalanine (Cha) as a substitute for Leu2. Both heterocycle-tetrapeptide and heterocycle-dipeptides displayed PAR2 specificity, however, only the heterocycle-tetrapeptides displayed full PAR2 agonism. Using the lipid-tethered-peptidomimetic approach we have developed novel structure activity relationships for PAR2 that allows for selective probing of PAR2 function across a broad range of physiological systems.
Targeting adenosine monophosphate-activated protein kinase (AMPK) in preclinical models reveals a potential mechanism for the treatment of neuropathic pain
Ohannes K Melemedjian, Marina N Asiedu, Dipti V Tillu, Raul Sanoja, Jin Yan, Arianna Lark, Arkady Khoutorsky, Jessica Johnson, Katherine A Peebles, Talya Lepow, Nahum Sonenberg, Gregory Dussor, Theodore J Price
Molecular Pain , 2011, DOI: 10.1186/1744-8069-7-70
Abstract: Neuropathic pain is a debilitating condition wherein a large cohort of patients fail to achieve even partial pain relief [1]. Hence, novel treatment approaches targeting molecular mechanisms of pathology induced by peripheral nerve injury (PNI) are needed. PNI leads to changes in sensory neuron phenotype and function resulting in hyperexcitability and ectopic activity in these neurons driving neuropathic pain [2]. The important role of translation regulation in learning and memory has elucidated translation control as a critical factor for neuronal plasticity [3]. Multiple lines of evidence suggest that translation regulation at the level of the primary afferent neuron is crucial for the establishment and maintenance of enhanced pain states [4-9]. Several recent reports have suggested an important role for the mammalian target of rapamycin complex 1 (mTORC1) pathway in neuropathic pain [4,6]; however, mechanistic links between mTORC1 and pathology induced by PNI are still lacking. Moreover, treatment strategies that target translation control have not been clearly identified as potential treatments for neuropathic pain.Translation control is orchestrated by upstream kinases that signal to the translation machinery [10]. These kinases can be targeted individually by selective inhibitors or they can be negatively modulated by endogenous signaling factors that act on these pathways [11]. A crucial kinase for negative regulation of translation is the ubiquitous, energy-sensing kinase AMP-activated protein kinase (AMPK). Activation of AMPK by depletion of cellular nutrients or through pharmacological intervention results in a dampening of signaling to the translation machinery [11] but the potential effects of AMPK activation on neuronal excitability, an important component of neuropathic pain conditions [2], is not known. AMPK can be targeted pharmacologically via a number of investigational compounds (e.g. AICAR and A769662) and by the widely clinically available and r
On the Theory of Topological Computation in the Lowest Landau Level of QHE  [PDF]
Dipti Banerjee
Journal of Quantum Information Science (JQIS) , 2011, DOI: 10.4236/jqis.2011.13017
Abstract: We have studied the formation of Hall-qubit in lowest Landau level of (LLL) Quantum Hall effect due to the Aharonov-Bhom oscillation of quasiparticles.The spin echo method plays the key role in the topological entanglement of qubits. The proper ratio of fluxes for maximally entangling qubits has also been pointed out. The generation of higher Quantum Hall state may be possible with the help of quantum teleportation.
Exploring the Efficacy & Suitability of Flipped Classroom Instruction at School Level in India: A Pilot Study  [PDF]
Atasi Mohanty, Dipti Parida
Creative Education (CE) , 2016, DOI: 10.4236/ce.2016.75079
Abstract: The objective of this study was to compare the impact of flipped mode and traditional mode of instruction, on the learning outcomes of Grade VIII school children in History and Science; 90 primary school children from Odisha (India) were randomly assigned to either of control (traditional instruction) or experimental (flipped instruction) group. Pre-test scores of both the groups were compared through “t” test; the obtained “t” values of -0.019 and 1.931 were found to be insignificant (p > 0.05) which revealed no significant difference between these groups at the beginning. Thus, both the groups were assumed to have equal variance and after 01 month their post-test scores in History and Science were again compared to examine the impact of different instructional intervention/s. The obtained “t” values of both the groups’ post-test scores comparisons were -5.592, -3.260, found to be significant at p < 0.01 level, and confirmed the difference between control and experimental groups. Mean scores of flipped and traditional instructional groups further strengthened the positive impact of flipped mode of instruction on children’s learning outcomes in History and Science. The study recommends for future work on flipped instruction with larger sample for educational implications.
DEVELOPMENT AND VALIDATION OF FIRST ORDER DERIVATIVE SPECTROPHOTOMETRIC METHOD FOR SIMULTANEOUS ESTIMATION DICLOXACILLIN AND CEFPODOXIME PROXETIL IN TABLET DOSAGE FORM
Acharya Drupad R,Patel Dipti B,Patel Vikram V
Journal of Drug Delivery and Therapeutics , 2012,
Abstract: The present manuscript describe simple, sensitive, rapid, accurate, precise and economical first derivative spectrophotometric method for the simultaneous determination of dicloxacillin and cefpodoxime proxetil in combined tablet dosage form. The derivative spectrophotometric method was based on the determination of both the drugs at their respective zero crossing point (ZCP). The first order derivative spectra was obtained in methanol and the determinations were made at 233.8 nm (ZCP of cefpodoxime proxetil) for dicloxacillin and 321 nm (ZCP of dicloxacillin) for cefpodoxime proxetil. The linearity was obtained in the concentration range of 10-80 μg/ml for dicloxacillin and 4-32 μg/ml for cefpodoxime proxetil. The mean recovery was 100.70 ± 0.38 and 99.90 ± 0.36 for dicloxacillin and cefpodoxime proxetil, respectively. The method was found to be simple, sensitive, accurate and precise and was applicable for the simultaneous determination of dicloxacillin and cefpodoxime proxetil in pharmaceutical tablet dosage form. The results of analysis have been validated statistically and by recovery studies.
Skin lesions in a 30-year-old male having smear-positive pulmonary tuberculosis
Gupta Prem,Jain V,Agarwal Dipti,Yaseer P
Annals of Thoracic Medicine , 2009,
Abstract:
A Novel Approach for Automatic Web Page Classification using Feature Intervals
J. Alamelu Mangai,Dipti D Kothari,V. Santhosh Kumar
International Journal of Computer Science Issues , 2012,
Abstract: A new web page classification algorithm using weighted voting of feature intervals known as WVFI is proposed in this paper. This classifier first discretizes the web page features using a supervised disctretization algorithm which identifies the number of intervals each feature has to be discretized automatically. Each feature is then made to predict the class of the corresponding feature in the test web page using the class distribution of its intervals. The final class of the test web page is predicted by aggregating the weighted vote of each feature. Experiments done on a benchmarking data set called WebKB has shown good classification accuracy when compared with many of the existing classifiers.
Cancer, Inflammation, and Insights from Ayurveda
Venil N. Sumantran,Girish Tillu
Evidence-Based Complementary and Alternative Medicine , 2012, DOI: 10.1155/2012/306346
Abstract: A recent, exciting discovery relates to the concept of “shared pathology” between cancer and metabolic syndrome. One major pathway common to cancer and metabolic syndrome is chronic inflammation, which is a major driving force in carcinogenesis. Indeed, chronic inflammation precedes most cancers and is considered a “hallmark” of the neoplastic process. We discuss molecular and biochemical evidence which links diet, obesity, abnormal lipid metabolism, and type 2 diabetes mellitus with chronic inflammation. We also explain how each of these factors is linked with biochemical aberrations of carcinogenesis and the prevalence and risk of cancer. While there are reliable biomarkers for chronic inflammation, there are few markers for a mechanistic link between early inflammation and digestive disorders. Discovery of such a marker could lead to identification of a new subtype of patients with digestive disorders that predispose them to cancer and/or metabolic syndrome. In this context, we discuss the ayurvedic concept of “Ama” which is thought to be a toxic, proinflammatory waste-product of improper digestion. We then develop hypotheses and outline preclinical and clinical experiments designed to prove whether “Ama” can serve as a novel and reliable biomarker that links abnormal digestive status, with the onset of chronic inflammation.
Antifungal Potential of Transition Metal Hexacyanoferrates against Fungal Diseases of Mushroom  [PDF]
Charu Arora Chugh, Dipti Bharti
Open Journal of Synthesis Theory and Applications (OJSTA) , 2012, DOI: 10.4236/ojsta.2012.13005
Abstract: Ferrocyanides of Co(II), Ni(II), Cu(II), Zn(II) and Cd(II) were synthesized and characterized by IR spectra, magnetic susceptibility, thermal gravimetric analysis, elemental analysis and X ray diffraction studies. Antimicrobial potential of these complexes have been evaluated. Antifungal screening of these complexes has been carried out against Mycogone perniciosa and Verticillium fungicola causing wet and dry bubble diseases of button mushroom respectively. Nickel ferrocyanide has been found to be most effective against Mycogone perniciosa with 60% inhibitory effect while cadmium ferrocyanide has exhibited significant potential of 85% against Verticillium fungicola.
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