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Find video protocols related to scientific articles indexed in Pubmed.
Direct vs. indirect pathway for nitrobenzene reduction reaction on a Ni catalyst surface: a density functional study.
Phys Chem Chem Phys
PUBLISHED: 11-04-2014
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Density functional theory (DFT) calculations are performed to understand and address the previous experimental results that showed the reduction of nitrobenzene to aniline prefers direct over indirect reaction pathways irrespective of the catalyst surface. Nitrobenzene to aniline conversion occurs via the hydroxyl amine intermediate (direct pathway) or via the azoxybenzene intermediate (indirect pathway). Through our computational study we calculated the spin polarized and dispersion corrected reaction energies and activation barriers corresponding to various reaction pathways for the reduction of nitrobenzene to aniline over a Ni catalyst surface. The adsorption behaviour of the substrate, nitrobenzene, on the catalyst surface was also considered and the energetically most preferable structural orientation was elucidated. Our study indicates that the parallel adsorption behaviour of the molecules over a catalyst surface is preferable over vertical adsorption behaviour. Based on the reaction energies and activation barrier of the various elementary steps involved in direct or indirect reaction pathways, we find that the direct reduction pathway of nitrobenzene over the Ni(111) catalyst surface is more favourable than the indirect reaction pathway.
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A new bulky iminophosphonamide as an N,N'-chelating ligand: synthesis and structural characterization of heteroleptic group 13 element complexes.
Dalton Trans
PUBLISHED: 10-10-2014
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A sterically demanding iminophosphonamine ligand [(2,6-iPr2C6H3N)P(Ph2)(NtBu)]H (LH) and its lithium derivative [(2,6-iPr2C6H3N)P(Ph2)(NtBu)](Li·2THF) () were used to prepare complexes of group 13 elements. The reaction of LH with AlH3·NMe2Et and AlMe3 respectively, affords [LAlH2]2 () and LAlMe2 (). The lithium derivative when treated with the MCl3 compound of group 13 yields [(2,6-iPr2C6H3N)P(Ph2)(NtBu)]MCl2 (M = B (); Al (); and Ga (). Compound on reaction with a Lewis acid B(C6F5)3 generates the cationic complex [{(2,6-iPr2C6H3N)P(Ph2)(NtBu)}AlMe](+) [MeB(C6F5)3](-) () that slowly undergoes rearrangement to yield [(2,6-iPr2C6H3N)P(Ph2)(NtBu)]AlMe(C6F5) () and MeB(C6F5)2. Compounds were characterized using multinuclear NMR, EI-MS and IR techniques and the solid state structure of and was elucidated by single crystal X-ray diffraction analyses.
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Gene-expression profiling elucidates molecular signaling networks that can be therapeutically targeted in vestibular schwannoma.
J. Neurosurg.
PUBLISHED: 09-24-2014
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Object Vestibular schwannomas (VS) are common benign tumors of the vestibular nerve that cause significant morbidity. The current treatment strategies for VS include surgery or radiation, with each treatment option having associated complications and side effects. The transcriptional landscape of schwannoma remains largely unknown. Methods In this study the authors performed gene-expression profiling of 49 schwannomas and 7 normal control vestibular nerves to identify tumor-specific gene-expression patterns. They also interrogated whether schwannomas comprise several molecular subtypes using several transcription-based clustering strategies. The authors also performed in vitro experiments testing therapeutic inhibitors of over-activated pathways in a schwannoma cell line, namely the PI3K/AKT/mTOR pathway. Results The authors identified over 4000 differentially expressed genes between controls and schwannomas with network analysis, uncovering proliferation and anti-apoptotic pathways previously not implicated in VS. Furthermore, using several distinct clustering technologies, they could not reproducibly identify distinct VS subtypes or significant differences between sporadic and germline NF2-associated schwannomas, suggesting that they are highly similar entities. The authors identified overexpression of PI3K/AKT/mTOR signaling networks in their geneexpression study and evaluated this pathway for therapeutic targeting. Testing the compounds BEZ235 and PKI-587, both novel dual inhibitors of PI3K and mTOR, attenuated tumor growth in a preclinical cell line model of schwannoma (HEI-293). In vitro findings demonstrated that pharmacological inhibition of the PI3K/AKT/mTOR pathway with next-generation compounds led to decreased cell viability and increased cell death. Conclusions These findings implicate aberrant activation of the PI3K/AKT/mTOR pathway as a molecular mechanism of pathogenesis in VS and suggest inhibition of this pathway as a potential treatment strategy.
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Mesenchymal chondrosarcoma of mandible: A rare case report and review.
J Oral Maxillofac Pathol
PUBLISHED: 09-04-2014
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Mesenchymal Chondrosarcomas (MCs) are rare malignant connective tissue neoplasms representing approximately 1% of all chondrosarcomas (CSs) that can arise from both soft and hard tissues. They are distinct tumors arising in unicentric or multicentric locations. The tumor is most unusual as it has been described as a particularly aggressive neoplasm with a high tendency for late recurrence and delayed metastasis. It is a biphasic tumor with areas comprising of spindle cell mesenchyme having areas of chondroid differentiation. Here we report a case of 60-year-old male with mesenchymal CS of the mandible.
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Investigations on agglomeration and haemocompatibility of vitamin E TPGS surface modified berberine chloride nanoparticles.
Biomed Res Int
PUBLISHED: 08-04-2014
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The objective of the present study is to investigate the influence of surface modification on systemic stability of NPs. Vitamin E TPGS (1% w/v) was used for surface modification of berberine chloride nanoparticles. Naked and surface modified NPs were incubated in different SBFs (pH 6.8 and 7.4) with or without bile salts and human plasma. NPs were observed for particle agglomeration and morphology by particle size analyzer and TEM, respectively. The haemocompatibility studies were conducted on developed NPs to evaluate their safety profile. The surface modified NPs were stable compared to naked NPs in different SBFs due to the steric stabilization property of vitamin E TPGS. Particle agglomeration was not seen when NPs were incubated in SBF (pH 6.8) with bile salts. No agglomeration was observed in NPs after their incubation in plasma but particle size of the naked NPs increased due to adhesion of plasma proteins. The TEM images confirmed the particle size results. DSC and FT-IR studies confirmed the coexistence of TPGS in surface modified NPs. The permissible haemolysis, LDH release, and platelet aggregation revealed that NPs were compatible for systemic administration. Thus, the study illustrated that the surface modification is helpful in the maintenance of stability of NPs in systemic conditions.
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Comparative Analysis of Glycogene Expression in Different Mouse Tissues Using RNA-Seq Data.
Int J Genomics
PUBLISHED: 07-09-2014
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Glycogenes regulate a wide array of biological processes in the development of organisms as well as different diseases such as cancer, primary open-angle glaucoma, and renal dysfunction. The objective of this study was to explore the role of differentially expressed glycogenes (DEGGs) in three major tissues such as brain, muscle, and liver using mouse RNA-seq data, and we identified 579, 501, and 442 DEGGs for brain versus liver (BvL579), brain versus muscle (BvM501), and liver versus muscle (LvM442) groups. DAVID functional analysis suggested inflammatory response, glycosaminoglycan metabolic process, and protein maturation as the enriched biological processes in BvL579, BvM501, and LvM442, respectively. These DEGGs were then used to construct three interaction networks by using GeneMANIA, from which we detected potential hub genes such as PEMT and HPXN (BvL579), IGF2 and NID2 (BvM501), and STAT6 and FLT1 (LvM442), having the highest degree. Additionally, our community analysis results suggest that the significance of immune system related processes in liver, glycosphingolipid metabolic processes in the development of brain, and the processes such as cell proliferation, adhesion, and growth are important for muscle development. Further studies are required to confirm the role of predicted hub genes as well as the significance of biological processes.
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VARIATIONS OF SOIL RADON CONCENTRATIONS ALONG CHITE FAULT IN AIZAWL DISTRICT, MIZORAM, INDIA.
Radiat Prot Dosimetry
PUBLISHED: 07-06-2014
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The present study concerns measurements of radon emissions from soil carried out during March to July 2013 at Chite fault in Aizawl district, Mizoram, India. In this study, continuous radon monitoring in soil was done by using LR-115 type II nuclear track detector (Kodak-Pathe, France make), and the exposed films were replaced weekly. A negative correlation coefficient (-0.47) between radon concentration and barometric pressure was found during the investigation period. The average radon concentration was observed to be 1785.71 Bq m(-3) with a standard deviation of 633.07 Bq m(-3). The maximum and minimum values of radon concentration during this period were found to be 3693.88 and 904.76 Bq m(-3), respectively. An anomalous increase in radon concentration was observed on 112th day (i.e. on 14 June 2013) during the investigation period just 1 d prior to the event of M 3.5, which occurred within 120-km distance from the monitoring site.
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Amitriptyline is efficacious in ameliorating muscle inflammation and depressive symptoms in the mdx mouse model of Duchenne muscular dystrophy.
Exp. Physiol.
PUBLISHED: 06-27-2014
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Mutations in the structural protein dystrophin underlie muscular dystrophies characterized by progressive deterioration of muscle function. Dystrophin-deficient mdx mice are considered a model for Duchenne muscular dystrophy (DMD). Individuals with DMD are also susceptible to mood disorders, such as depression and anxiety. Therefore, the study objectives were to investigate the effects of the tricyclic antidepressant amitriptyline on mood, learning, central cytokine expression and skeletal muscle inflammation in mdx mice. Amitriptyline-induced effects (10 mg kg(-1) daily s.c. injections, 25 days) on the behaviour of mdx mice were investigated using the open field arena and tail suspension tests. The effects of chronic amitriptyline treatment on inflammatory markers were studied in the muscle and plasma of mdx mice, and mood-associated monoamine and cytokine concentrations were measured in the amygdala, hippocampus, prefrontal cortex, striatum, hypothalamus and midbrain. The mdx mice exhibited increased levels of anxiety and depressive-like behaviour compared with wild-type mice. Amitriptyline treatment had anxiolytic and antidepressant effects in mdx mice associated with elevations in serotonin levels in the amygdala and hippocampus. Inflammation in mdx skeletal muscle tissue was also reduced following amitriptyline treatment as indicated by decreased immune cell infiltration of muscle and lower levels of the pro-inflammatory cytokines tumour necrosis factor-? and interleukin-6 in the forelimb flexors. Interleukin-6 mRNA expression was remarkably reduced in the amygdala of mdx mice by chronic amitriptyline treatment. Positive effects of amitriptyline on mood, in addition to its anti-inflammatory effects in skeletal muscle, may make it an attractive therapeutic option for individuals with DMD.
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High prevalence of asymptomatic malaria in apparently healthy schoolchildren in Aliero, Kebbi state, Nigeria.
J Vector Borne Dis
PUBLISHED: 06-21-2014
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In malaria endemic areas, continuous exposure to Plasmodium parasites leads to asymptomatic carriers that provide a reservoir, contributing to the persistence of malaria transmission. Thus, a study of the degree of prevalence of asymptomatic parasitaemias will help in assessing the level of reservoir of infection.
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A role for matrix remodeling proteins in invasive and malignant meningiomas.
Neuropathol. Appl. Neurobiol.
PUBLISHED: 06-10-2014
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Meningiomas are one of the most common brain tumors in adults. Invasive and malignant meningiomas present a significant therapeutic challenge due to high recurrence rates and invasion into surrounding bone, brain, neural and soft tissues. Understanding the molecular mechanism of invasion could help in designing novel therapeutic approaches in order to prevent the need for repeat surgery, decrease morbidity and improve patient survival. The aim of this study was to identify the key factors and underlying mechanisms which govern invasive properties of meningiomas.
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Solubilized delivery of paliperidone palmitate by d-alpha-tocopheryl polyethylene glycol 1000 succinate micelles for improved short-term psychotic management.
Drug Deliv
PUBLISHED: 05-24-2014
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Abstract The objective of this work was to formulate paliperidone palmitate-loaded d-alpha-tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS or TPGS) micelles for improved antipsychotic effect during short-term management of psychotic disorders. Vitamin E TPGS micelles containing paliperidone palmitate were prepared by the solvent casting method and control paliperidone palmitate formulations were prepared by simple sonication method. The prepared micelles and control paliperidone palmitate formulations were evaluated for different parameters. Particle sizes of prepared micelles, control paliperidone palmitate formulations were determined at 25?°C by dynamic light scattering technique and external surface morphology was determined by transmission electron microscopy analysis. The encapsulation efficiency was determined by spectrophotometery. In-vitro release studies of micelles and control formulations were carried out by dialysis bag diffusion method. The particle sizes of the paliperidone palmitate-loaded TPGS micelles were 26.5?nm. About 92% of drug encapsulation efficiency was achieved with micelles. The drug release from paliperidone palmitate-loaded TPGS micelles was sustained for more than 24?h with 40% of drug release. The TPGS product, i.e. paliperidone palmitate-loaded micelles, resulted in nano-sized delivery, solubility enhancement and permeability of the micelles which provided an improved and prolonged anti-psychotic effect in comparison to control paliperidone palmitate formulation.
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Development of polymeric nanoparticles with highly entrapped herbal hydrophilic drug using nanoprecipitation technique: an approach of quality by design.
Pharm Dev Technol
PUBLISHED: 05-17-2014
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Abstract The intention of this study is to achieve higher entrapment efficiency (EE) of berberine chloride (selected hydrophilic drug) using nanoprecipitation technique. The solubility of drug was studied in various pH buffers (1.2-7.2) for selection of aqueous phase and stabilizer. Quality by design (QbD)-based 3(2) factorial design were employed for optimization of formulation variables; drug to polymer ratio (X1) and surfactant concentration (X2) on entrapment efficiency (EE), particle size (PS) and polydispersity index (PDI) of the nanoparticles. The nanoparticles were subjected to solid state analysis, in vitro drug release and stability study. The aqueous phase and stabilizer selected for the formulations were pH 4.5 phthalate buffer and surfactant F-68, respectively. The formulation (F-6) containing drug to polymer ratio (1:3) and stabilizer (F-68) concentration of 50?mM exhibited best EE (82.12%), PS (196.71?nm), PDI (0.153). The various solid state characterizations assured that entrapped drug is amorphous and nanoparticles are fairly spherical in shape. In vitro drug release of the F-6 exhibited sustained release with non-Fickian diffusion and stable at storage condition. This work illustrates that the proper selection of aqueous phase and optimization of formulation variables could be helpful in improving the EE of hydrophilic drugs by nanoprecipitation technique.
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VEGF regulates region-specific localization of perivascular bone marrow-derived cells in glioblastoma.
Cancer Res.
PUBLISHED: 05-12-2014
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Glioblastoma multiforme (GBM) is characterized by a pathogenic vasculature that drives aggressive local invasion. Recent work suggests that GBM cells recruit bone marrow-derived progenitor cells (BMDC) to facilitate recurrence after radiotherapy, but how this may be achieved is unclear. In this study, we established the spatiotemporal and regional contributions of perivascular BMDCs (pBMDC) to GBM development. We found an increased recruitment of BMDCs to GBM in response to tumor growth and following radiotherapy. However, in this study, BMDCs did not differentiate into endothelial cells directly but rather provided a perivascular support role. The pBMDCs were shown to associate with tumor vasculature in a highly region-dependent manner, with central vasculature requiring minimal pBMDC support. Region-dependent association of pBMDC was regulated by VEGF. In the absence of VEGF, following radiotherapy or antiangiogenic therapy, we documented an increase in Ang2 that regulated recruitment of pBMDCs to maintain the vulnerable central vasculature. Together, our results strongly suggested that targeting pBMDC influx along with radiation or antiangiogenic therapy would be critical to prevent vascular recurrence of GBM.
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Knowledge, attitude and practices on malaria among the rural communities in aliero, northern Nigeria.
J Family Med Prim Care
PUBLISHED: 05-03-2014
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Families' perceptions, beliefs, and attitudes about malaria causation, symptom identification, treatment of malaria, and prevention are often overlooked in malaria control efforts. This study was conducted to understand these issues, which can be an important step towards developing strategies, aimed at controlling malaria.
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Refractory status epilepticus.
Ann Indian Acad Neurol
PUBLISHED: 05-03-2014
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Refractory status epilepticus is a potentially life-threatening medical emergency. It requires early diagnosis and treatment. There is a lack of consensus upon its semantic definition of whether it is status epilepticus that continues despite treatment with benzodiazepine and one antiepileptic medication (AED), i.e., Lorazepam + phenytoin. Others regard refractory status epilepticus as failure of benzodiazepine and 2 antiepileptic medications, i.e., Lorazepam + phenytoin + phenobarb. Up to 30% patients in SE fail to respond to two antiepileptic drugs (AEDs) and 15% continue to have seizure activity despite use of three drugs. Mechanisms that have made the treatment even more challenging are GABA-R that is internalized during status epilepticus and upregulation of multidrug transporter proteins. All patients of refractory status epilepticus require continuous EEG monitoring. There are three main agents used in the treatment of RSE. These include pentobarbital or thiopental, midazolam and propofol. RSE was shown to result in mortality in 35% cases, 39.13% of patients were left with severe neurological deficits, while another 13% had mild neurological deficits.
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Magnetoencephalography: Basic principles.
Ann Indian Acad Neurol
PUBLISHED: 05-03-2014
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Magnetoencephalography (MEG) is the measurement of the magnetic field generated by the electrical activity of neurons. It is usually combined with a magnetic resonance imaging to get what is called magnetic source imaging. The technology that has helped record these minute magnetic fields is super-conducting quantum interference detector which is like a highly sensitive magnetic field meter. To attenuate the external magnetic noise the MEG is housed inside a magnetically shielded room. The actual sensors recording magnetic fields are magnetometers and/or gradiometers. MEG fields pass through the head without any distortion. This is a significant advantage of MEG over electroencephalography. MEG provides a high spatial and temporal resolution. The recording and identification information should be according to the American Clinical Magnetoencephalography Society guidelines published in 2011. MEG currently has two approved indications in the United States, one is for pre-operative brain mapping and the other is for use in epilepsy surgery. MEG studies have shown functional brain tissue inside brain tumors.
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MRI biomarkers identify the differential response of glioblastoma multiforme to anti-angiogenic therapy.
Neuro-oncology
PUBLISHED: 04-23-2014
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Although anti-angiogenic therapy (AATx) holds great promise for treatment of malignant gliomas, its therapeutic efficacy is not well understood and can potentially increase the aggressive recurrence of gliomas. It is essential to establish sensitive, noninvasive biomarkers that can detect failure of AATx and tumor recurrence early so that timely adaptive therapy can be instituted. We investigated the efficacy of MRI biomarkers that can detect response to different classes of AATxs used alone or in combination with radiation.
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Cefuroxime axetil loaded solid lipid nanoparticles for enhanced activity against S. aureus biofilm.
Colloids Surf B Biointerfaces
PUBLISHED: 03-25-2014
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The present research work is focused on the development of solid lipid nanoparticles of cefuroxime axetil (CA-SLN) for its enhanced inhibitory activity against Staphylococcus aureus produced biofilm. CA-SLN was prepared by solvent emulsification/evaporation method using single lipid (stearic acid (SA)) and binary lipids (SA and tristearin (TS)). Process variables such as volume of dispersion medium, concentration of surfactant, homogenization speed and time were optimized. The prepared SLN were characterized for encapsulation efficiency, drug polymer interaction studies (DSC and FT-IR), shape and surface morphology (SEM and AFM), in vitro drug release, stability studies and in vitro anti biofilm activity against S. aureus biofilm. Among the process variables, increased volume of dispersion medium, homogenization speed and time led to increase in particle size whereas increase in surfactant concentration decreased the particle size. SLN prepared using binary lipids exhibited higher entrapment efficiency than the single lipid. DSC and FT-IR studies showed no incompatible interaction between drug and excipients. CA-SLN showed two folds higher anti-biofilm activity in vitro than pristine CA against S. aureus biofilm.
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GBM's multifaceted landscape: highlighting regional and microenvironmental heterogeneity.
Neuro-oncology
PUBLISHED: 03-18-2014
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Gliomas are a heterogeneous group of tumors that show variable proliferative potential, invasiveness, aggressiveness, histological grading, and clinical behavior. In this review, we focus on glioblastoma multiforme (GBM), a grade IV glioma, which is the most common and malignant of primary adult brain tumors. Research over the past several decades has revealed the existence of extensive cellular, molecular, genetic, epigenetic, and metabolic heterogeneity among tumors of the same grade and even within individual tumors. Evaluation of different tumor types has shown that tumors with advanced grade and clinical aggressiveness also display enhanced molecular, cellular, and microenvironmental heterogeneity. From a therapeutic standpoint, this heterogeneity is a major clinical hurdle for devising effective therapeutic strategies for patients and challenges personalized medicine. In this review, we will highlight key aspects of GBM heterogeneity, directing special attention to regional heterogeneity, hypoxia, genomic heterogeneity, tumor-specific metabolic reprogramming, neovascularization or angiogenesis, and stromal immune cells. We will further discuss the clinical implications of GBM heterogeneity in the context of therapy.
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Antidiabetic potential of triterpenoid saponin isolated from Primula denticulate.
Pharm Biol
PUBLISHED: 03-12-2014
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Primula denticulate Sm. (Primulaceae), commonly known as drumstick primula, is traditionally used to treat diabetes and urinary disorders. In the present study, a new triterpenoid saponin was isolated. Triterpenoids generally show antidiabetic activity. Considering its traditional use and chemical nature of the molecule, the present study was designed to evaluate the antidiabetic activity. Objective: Antidiabetic activity of triterpenoid saponin (TTS) isolated from P. denticulate.
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Clinical evaluation of analgesic activity of guduchi (tinospora cordifolia) using animal model.
J Clin Diagn Res
PUBLISHED: 03-09-2014
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Pain is a very well-known signal of ill health and analgesics are the drugs that are used to relieve pain. The main problem with these drugs remains that of side effects. Safer alternatives are natural herbs. Guduchi (Tinospora cordifolia) is one such plant with analgesic potential but few studies are there.
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Room-temperature chemoselective reduction of nitro groups using non-noble metal nanocatalysts in water.
Inorg Chem
PUBLISHED: 02-24-2014
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Purely aqueous-phase chemoselective reduction of a wide range of aromatic and aliphatic nitro substrates has been performed in the presence of inexpensive Ni- and Co-based nanoparticle catalysts using hydrazine hydrate as a reducing agent at room temperature. Along with the observed high conversions and selectivities, the studied nanoparticle catalysts also exhibit a high tolerance to other highly reducible groups present in the nitro substrates. The development of these potential chemoselective reduction catalysts also provides a facile route for the synthesis of other industrially important fine chemicals or biologically important compounds, where other highly reducible groups are present in close proximity to the targeted nitro groups.
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Multicentric aggressive mammary fibromatosis with cytological features and review of literature.
J Clin Diagn Res
PUBLISHED: 02-13-2014
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Fibromatosis is a fibroblastic lesion composed of uniform fibroblasts and collagen with an infiltrative growth pattern but lacking malignant cytological features. It is a rare entity and is even more unusual when found in the breast. Multicentricity in fibromatosis has been reported in 10% cases. Multicentricity in breast cancer has been defined as the presence of two or more tumor foci within different quadrants of the same breast. Considering this definition of multicentricity for fibromatosis, we herein report a case of recurrent multicentric aggressive mammary fibromatosis and its cytological features with review of literature because of limited literature of (FNAC) in mammary fibromatosis.
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Structural functional and folding scenario of an anti platelet and thrombolytic enzyme crinumin.
Int. J. Biol. Macromol.
PUBLISHED: 01-30-2014
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A folding pattern, conformational stability and therapeutic role of a protein helps in developing a suitable drug. Crinumin, a thrombolytic and anti platelet agent, has been studied for its functional and conformational properties by equilibrium unfolding methods. The crinumin belongs to ?+? class of protein and exhibits a non native structure and two molten globule states at different conditions. Two domains in the molecular structure of the protein with altered stability are present that unfold sequentially. The enzyme maintains activity as well as structural integrity even in adverse conditions. These observations provide an understanding of protein folding as well as facilitate the development of a potential drug.
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Mucoadhesive hydrogel films of econazole nitrate: formulation and optimization using factorial design.
J Drug Deliv
PUBLISHED: 01-24-2014
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The mucoadhesive hydrogel film was prepared and optimized for the purpose of local drug delivery to oral cavity for the treatment of oral Candidiasis. The mucoadhesive hydrogel film was prepared with the poly(vinyl alcohol) by freeze/thaw crosslinking technique. 3(2) full factorial design was employed to optimize the formulation. Number of freeze/thaw cycles (4, 6, and 8 cycles) and the concentration of the poly(vinyl alcohol) (10, 15, and 20%) were used as the independent variables whereas time required for 50% drug release, cumulative percent of drug release at 8th hour, and "k" of zero order equation were used as the dependent variables. The films were evaluated for mucoadhesive strength, in vitro residence time, swelling study, in vitro drug release, and effectiveness against Candida albicans. The concentration of poly(vinyl alcohol) and the number of freeze/thaw cycles both decrease the drug release rate. Mucoadhesive hydrogel film with 15% poly(vinyl alcohol) and 7 freeze/thaw cycles was optimized. The optimized batch exhibited the sustained release of drug and the antifungal studies revealed that the drug released from the film could inhibit the growth of Candida albicans for 12 hours.
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A review on skin targeted delivery of bioactives as ultradeformable vesicles: overcoming the penetration problem.
Curr Drug Targets
PUBLISHED: 01-14-2014
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Administration of drugs through skin via transdermal route is a non-invasive approach and applicable for systemic delivery but it is not suitable for drugs having higher molecular weight. Various approaches have been used to improve the efficacy of transdermal route such as vesicular system, iontophoresis, microneedles, use of permeation enhancers, etc. Among the several approaches, vesicular delivery is gaining importance in transdermal drug delivery. Transfersomes are one of the vesicular systems and they are best suited for the transdermal delivery of higher molecular weight compounds. Due to the deformable nature of transfersomes, they penetrate into deeper layers of skin, retain their original structure after penetration and finally enter into the systemic circulation. This review focuses mainly on the applications of transfersomes in the field of drug delivery i.e. delivery of analgesics, anti-cancers, proteins and peptides, immunomodulators, steroidal hormones and herbal drugs with increased penetration through skin. In addition, this review also deals with preparation methods available for preparing transfersomes, characterization, mechanism of penetration upon topical application and its kinetic aspects.
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Targeting of diacerein loaded lipid nanoparticles to intra-articular cartilage using chondroitin sulfate as homing carrier for treatment of osteoarthritis in rats.
Nanomedicine
PUBLISHED: 01-08-2014
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Targeted delivery of antiosteoarthritic drug diacerein to articular tissue could be a major achievement and soluble polysaccharide chondroitin sulfate (ChS) may be a suitable agent for this. Therefore, diacerein loaded solid lipid nanoparticles modified with ChS (ChS-DC-SLN) were prepared for synergistic effect of these agents to combat multidimensional pathology of osteoarthritis (OA). Prepared formulation were of size range 396±2.7nm, showed extended release up to 16h and increased bioavailability of diacerein by 2.8 times. ChS-DC-SLN were evaluated for their effect on histopathology of femoro-tibial joint of rat knee and amount of ChS and rhein (an active metabolite of diacerein) at targeted site. Concentration of rhein was significantly higher in case of ChS-DC-SLN (7.8±1.23?g/ml) than that of drug dispersion (2.9±0.45?g/ml). It can be stated that ChS served as homing to articular cartilage for targeting of drug. Thus, ChS-DC-SLN have great potential to enhance the overall efficacy of treatment for OA.
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Hypomagnesemia in hemodialysis patients: role of proton pump inhibitors.
Am. J. Nephrol.
PUBLISHED: 01-03-2014
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Recent observations have associated hypomagnesemia with increased risk of cardiovascular morbidity and mortality in hemodialysis patients.
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Withaferin a alone and in combination with Cisplatin suppresses growth and metastasis of ovarian cancer by targeting putative cancer stem cells.
PLoS ONE
PUBLISHED: 01-01-2014
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Currently, the treatment for ovarian cancer entails cytoreductive surgery followed by chemotherapy, mainly, carboplatin combined with paclitaxel. Although this regimen is initially effective in a high percentage of cases, unfortunately within few months of initial treatment, tumor relapse occurs because of platinum-resistance. This is attributed to chemo-resistance of cancer stem cells (CSCs). Herein we show for the first time that withaferin A (WFA), a bioactive compound isolated from the plant Withania somnifera, when used alone or in combination with cisplatin (CIS) targets putative CSCs. Treatment of nude mice bearing orthotopic ovarian tumors generated by injecting human ovarian epithelial cancer cell line (A2780) with WFA and cisplatin (WFA) alone or in combination resulted in a 70 to 80% reduction in tumor growth and complete inhibition of metastasis to other organs compared to untreated controls. Histochemical and Western blot analysis of the tumors revealed that inclusion of WFA (2 mg/kg) resulted in a highly significant elimination of cells expressing CSC markers - CD44, CD24, CD34, CD117 and Oct4 and downregulation of Notch1, Hes1 and Hey1 genes. In contrast treatment of mice with CIS alone (6 mg/kg) had opposite effect on those cells. Increase in cells expressing CSC markers and Notch1 signaling pathway in tumors exposed to CIS may explain recurrence of cancer in patients treated with carboplatin and paclitaxel. Since, WFA alone or in combination with CIS eliminates putative CSCs, we conclude that WFA in combination with CIS may present more efficacious therapy for ovarian cancer.
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An overview of the gene regulatory network controlling trichome development in the model plant, Arabidopsis.
Front Plant Sci
PUBLISHED: 01-01-2014
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Trichomes are specialized epidermal cells located on aerial parts of plants and are associated with a wide array of biological processes. Trichomes protect plants from adverse conditions including UV light and herbivore attack and are also an important source of a number of phytochemicals. The simple unicellular trichomes of Arabidopsis serve as an excellent model to study molecular mechanism of cell differentiation and pattern formation in plants. The emerging picture suggests that the developmental process is controlled by a transcriptional network involving three major groups of transcription factors (TFs): the R2R3 MYB, basic helix-loop-helix (bHLH), and WD40 repeat (WDR) protein. These regulatory proteins form a trimeric activator complex that positively regulates trichome development. The single repeat R3 MYBs act as negative regulators of trichome development. They compete with the R2R3 MYBs to bind the bHLH factor and form a repressor complex. In addition to activator-repressor mechanism, a depletion mechanism may operate in parallel during trichome development. In this mechanism, the bHLH factor traps the WDR protein which results in depletion of WDR protein in neighboring cells. Consequently, the cells with high levels of bHLH and WDR proteins are developed into trichomes. A group of C2H2 zinc finger TFs has also been implicated in trichome development. Phytohormones, including gibberellins and jasmonic acid, play significant roles in this developmental process. Recently, microRNAs have been shown to be involved in trichome development. Furthermore, it has been demonstrated that the activities of the key regulatory proteins involved in trichome development are controlled by the 26S/ubiquitin proteasome system (UPS), highlighting the complexity of the regulatory network controlling this developmental process. To complement several excellent recent relevant reviews, this review focuses on the transcriptional network and hormonal interplay controlling trichome development in Arabidopsis.
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Heterocyclic core analogs of a direct thrombin inhibitor.
Bioorg. Med. Chem. Lett.
PUBLISHED: 01-01-2014
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Thrombin is a serine protease that plays a key role in blood clotting. Pyrrolidine 1 is a potent thrombin inhibitor discovered at Merck several years ago. Seven analogs (2-8) of 1 in which the pyrrolidine core was replaced with various heterocycles were prepared and evaluated for activity against thrombin, clotting factors VIIa, IXa, Xa, and XIIa, and trypsin. The thiomorpholine analog 6 was the most active, essentially matching the thrombin inhibitory activity of 1 with slightly improved selectivity over trypsin.
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Coenzyme Q10 production in plants: current status and future prospects.
Crit. Rev. Biotechnol.
PUBLISHED: 10-05-2013
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Abstract Coenzyme Q10 (CoQ10) or Ubiquinone10 (UQ10), an isoprenylated benzoquinone, is well-known for its role as an electron carrier in aerobic respiration. It is a sole representative of lipid soluble antioxidant that is synthesized in our body. In recent years, it has been found to be associated with a range of patho-physiological conditions and its oral administration has also reported to be of therapeutic value in a wide spectrum of chronic diseases. Additionally, as an antioxidant, it has been widely used as an ingredient in dietary supplements, neutraceuticals, and functional foods as well as in anti-aging creams. Since its limited dietary uptake and decrease in its endogenous synthesis in the body with age and under various diseases states warrants its adequate supply from an external source. To meet its growing demand for pharmaceutical, cosmetic and food industries, there is a great interest in the commercial production of CoQ10. Various synthetic and fermentation of microbial natural producers and their mutated strains have been developed for its commercial production. Although, microbial production is the major industrial source of CoQ10 but due to low yield and high production cost, other cost-effective and alternative sources need to be explored. Plants, being photosynthetic, producing high biomass and the engineering of pathways for producing CoQ10 directly in food crops will eliminate the additional step for purification and thus could be used as an ideal and cost-effective alternative to chemical synthesis and microbial production of CoQ10. A better understanding of CoQ10 biosynthetic enzymes and their regulation in model systems like E. coli and yeast has led to the use of metabolic engineering to enhance CoQ10 production not only in microbes but also in plants. The plant-based CoQ10 production has emerged as a cost-effective and environment-friendly approach capable of supplying CoQ10 in ample amounts. The current strategies, progress and constraints of CoQ10 production in plants are discussed in this review.
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Facial nerve injury following surgery for temporomandibular joint ankylosis: a prospective clinical study.
Indian J Dent Res
PUBLISHED: 09-20-2013
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The purpose of this prospective study was to evaluate the incidence and degree of facial nerve damage and time taken for its recovery following surgery for temporomandibular joint (TMJ) ankylosis.
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Targeting of eugenol-loaded solid lipid nanoparticles to the epidermal layer of human skin.
Nanomedicine (Lond)
PUBLISHED: 08-30-2013
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Aim: The purpose of this study was to formulate carbopol hydrogels containing eugenol-loaded solid lipid nanoparticles (EG-SLNs) for epidermal targeting to treat fungal infections in skin. Materials & methods: EG-SLNs were incorporated into carbopol hydrogels and the physiochemical characteristics of EG-SLN in hydrogels were investigated by dynamic light scattering, transmission electron microscopy and atomic force microscopy. Rheological behavior and mechanical properties of hydrogels were also studied before and after incorporation of EG-SLNs. The epidermal-targeting ability of EG-SLN-enriched hydrogels was evaluated by estimation of eugenol in the epidermis of human cadaver skin. An occlusion (hydration) study was also performed to elucidate the mechanism of epidermal targeting of EG-SLN-enriched hydrogels. Results: The particle size (d90) and morphology of EG-SLNs were not significantly changed after incorporation into the hydrogel. EG-SLN of stearic acid-enriched hydrogels follow the Carreau model that describes pseudoplastic flow. The hydrogel containing EG-SLN of stearic acid and of Compritol(®) (Gattefose, Mumbai, India) showed significantly greater accumulation of eugenol in the epidermis (62.65 ± 4.35 and 52.86 ± 3.76 µg/cm(2), respectively) than that of eugenol-hydroxypropyl-?-cyclodextrin complex in hydrogel (9.77 ± 1.16 µg/cm(2)) and almond oil solution of eugenol (3.45 ± 0.6 µg/cm(2)). The occlusion study demonstrated greater hydration of human cadaver skin treated with EG-SLN-enriched hydrogel compared with that of hydrogel and intact skin. Conclusion: Hydrogels containing EG-SLNs could be a promising formulation for epidermal targeting to treat fungal infections in skin. Original submitted 26 March 2012; Revised submitted 29 January 2013.
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Hypertrophy of neurons within cardiac ganglia in human, canine, and rat heart failure: the potential role of nerve growth factor.
J Am Heart Assoc
PUBLISHED: 08-21-2013
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Autonomic imbalances including parasympathetic withdrawal and sympathetic overactivity are cardinal features of heart failure regardless of etiology; however, mechanisms underlying these imbalances remain unknown. Animal model studies of heart and visceral organ hypertrophy predict that nerve growth factor levels should be elevated in heart failure; whether this is so in human heart failure, though, remains unclear. We tested the hypotheses that neurons in cardiac ganglia are hypertrophied in human, canine, and rat heart failure and that nerve growth factor, which we hypothesize is elevated in the failing heart, contributes to this neuronal hypertrophy.
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Differential transformation capacity of neuro-glial progenitors during development.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 08-13-2013
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Gliomas represent the most common type of brain tumor, but show considerable variability in histologic appearance and clinical outcome. The phenotypic differences between types and grades of gliomas have not been explained solely on the grounds of differing oncogenic stimuli. Several studies have demonstrated that some phenotypic differences may be attributed to regional differences in the neural stem cells from which tumors arise. We hypothesized that temporal differences may also play a role, with tumor phenotypic variability reflecting intrinsic differences in neural stem cells at distinct developmental stages. To determine how the tumorigenic potential of lineally related stem cells changes over time, we used a conditional transgenic system that integrates Cre-Lox-mediated and Tet-regulated expression to drive K-ras(G12D) expression in neuro-glial progenitor populations at different developmental time points. Using this model, we demonstrate that K-ras(G12D)-induced transformation is dependent on the developmental stage at which it is introduced. Diffuse malignant brain tumors develop during early embryogenesis but not when K-ras(G12D) expression is induced during late embryogenesis or early postnatal life. We show that differential expression of cell-cycle regulators during development may be responsible for this differing susceptibility to malignant transformation and that loss of p53 can overcome the transformation resistance seen at later developmental stages. These results highlight the interplay between genetic alterations and the molecular changes that accompany specific developmental stages; early progenitors may lack the regulatory mechanisms present at later, more lineage-restrictive, developmental time points, making them more susceptible to transformation.
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Matched case-control study to examine association of psoriasis and migratory glossitis in India.
Indian J Dermatol Venereol Leprol
PUBLISHED: 07-19-2013
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Psoriasis is a multifactorial disease. Genetic and environmental factors, which determine the disease epidemiology and clinical spectrum, are heterogeneous in different populations. A few case-control studies from other countries have shown an association between psoriasis and migratory glossitis (MG). The characteristics of the association (e.g. relationship with gender, severity of psoriasis, early- versus late-onset psoriasis, etc.) have not been clearly defined.
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Development of lipid nanoparticles of diacerein, an antiosteoarthritic drug for enhancement in bioavailability and reduction in its side effects.
J Biomed Nanotechnol
PUBLISHED: 06-28-2013
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Osteoarthritis is the most common, multi component joint disease mainly characterized by destruction of articular cartilage which leads up to subchondral bone. Current treatment by NSAIDs gives only symptomatic relief but semi-synthetic anthraquinone diacerein is novel chondroprotective agent intended for the treatment of osteoarthritis. Its active metabolite rhein inhibits the agents responsible for cartilage degradation. In the present study, stearic acid, long chain fatty acids, based solid lipid nanoparticles were prepared with enhanced oral bioavailability and lesser side effects. Diacerein loaded solid lipid nanoparticles were prepared by modified high shear homogenization with ultrasonication method using stearic acid as lipid. Pluronic F68 and soya lecithin was used as surfactant. Citric acid was added to give acidic environment to drug. Solid lipid nanoparticles were evaluated for different characterization parameters, in-vitro performance and in-vivo pharmacokinetics and anti-diarrhoeal study. Particle size of the diacerein loaded SLN was found in the range of 270 +/- 2.1 to 510 +/- 2.8 nm with zeta potential -13.78 +/- 3.4 mV to -19.66 +/- 2.1 mV. Maximum entrapment efficiency was achieved up to 88.1 +/- 1.3%. Surface and solid state characterization by TEM, XRD and DSC revealed that all particles are spherical in shape and drug entrapped inside lipid was in amorphous state. In-vitro release was done by dialysis bag method in phosphate buffer (pH 5.8) which showed controlled and extended release profile up to 12 hr. In-vivo pharmacokinetic study reveals an increase in Area Under Curve from 26.68 +/- 1.63 to 71.25 +/- 1.25 hr microg ml(-1). Further diarrhoeal side effect of diacerein was also found to reduce up to 37% by lipid nanoparticles. These results suggest that diacerein loaded solid lipid nanoparticles can be prepared efficiently with stearic acid and produces controlled and prolonged drug release profile. The oral bioavailability was enhanced by around 2.7 times and with lesser diarrhoeal side effects. These all will leads to overall improvement in patient compliance for the treatment.
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Au-based bimetallic nanoparticles for the intramolecular aminoalkene hydroamination.
Dalton Trans
PUBLISHED: 06-15-2013
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Bimetallic Au-based nanoparticles (Au-M where M = Pt, Pd, Cu, Ni), synthesized by simultaneous reduction of the Au salt with noble/non-noble metal salts, exhibit a high activity for the aminoalkene (2,2-diphenylpent-4-en-1-amine) hydroamination affording the 5-membered Markovnikov product. Even though the particle size and morphology of Au-M nanoparticles are comparable to the corresponding monometallic Au nanoparticles, Au-M nanoparticles display superior catalytic activity, where the selectivity for the formation of the hydroaminated product depends on the alloying metal component in the bimetallic Au nanoparticle catalyst.
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(3 + 1)D superspace description of the incommensurate modulation in the premartensite phase of Ni2MnGa: a high resolution synchrotron x-ray powder diffraction study.
J Phys Condens Matter
PUBLISHED: 05-09-2013
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Le Bail and Rietveld analysis of high resolution synchrotron x-ray powder diffraction (SXRPD) data shows unambiguous signatures of the failure of the commensurate 3M modulation model. Using (3 + 1) dimensional superspace group formalism, we have not only confirmed the incommensurate modulation in the premartensite phase with a modulation wavevector of q = 0.337 61(5)c* but also determined the superspace group (Immm(00?)s00), atomic positions and amplitude of modulations for the incommensurate premartensite phase of Ni2MnGa for the first time. Our results may have important implications in the understanding of the martensitic transition and hence the magnetic field induced strains.
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Auxarthronopsis, a new genus of Onygenales isolated from the vicinity of Bandhavgarh National Park, India.
IMA Fungus
PUBLISHED: 04-17-2013
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An interesting onygenalean ascomycete was isolated from soil collected from a hollow tree near Bandhavgarh National Park situated in central India. The keratinophilic nature associated with a malbranchea-like asexual morph, appendaged mesh-like reticuloperidia, and subglobose to oblate, punctate ascospores, support the inclusion of this isolate in Onygenaceae. Further, the pale cream ascomata, punctate ascospores, and swollen septa in the peridial hyphae suggested that this was a new species of Auxarthron. However, phylogenetic study of LSU, SSU and ITS sequences, and presence of more than three swollen septa on the peridial appendages, do not support a placement within Auxarthron, and the new generic name Auxarthronopsis is introduced to accommodate this new fungus. The distinguishing features of this new taxon are the multiple (?10) swollen septa on the appendages attached to its reticulate, loosely mesh-like peridium, the finely and regularly punctate ascospores, and the production of arthroconidial and aleurioconidial asexual forms. Sequence analysis of ITS1-5.8S-ITS2, SSU and LSU regions clearly separate this fungus from monophyletic Auxarthron and other taxa bearing some morphological similarity. Phylogenetically, Auxarthronopsis bandhavgarhensis gen. sp. nov. is closest to Amauroascus purpureus, A. volatilis-patellis, Nannizziopsis albicans, and Renispora flavissima, but differs morphologically.
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Development and evaluation of solid lipid nanoparticles of raloxifene hydrochloride for enhanced bioavailability.
Biomed Res Int
PUBLISHED: 04-13-2013
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Raloxifene hydrochloride (RL-HCL) is an orally selective estrogen receptor modulator (SERM) with poor bioavailability of nearly 2% due to its poor aqueous solubility and extensive first pass metabolism. In order to improve the oral bioavailability of raloxifene, raloxifene loaded solid lipid nanoparticles (SLN) have been developed using Compritol 888 ATO as lipid carrier and Pluronic F68 as surfactant. Raloxifene loaded SLN were prepared by solvent emulsification/evaporation method, and different concentrations of surfactant, and homogenization speed were taken as process variables for optimization. SLN were characterized for particle size, zeta potential, entrapment efficiency, surface morphology, and crystallinity of lipid and drug. In vitro drug release studies were performed in phosphate buffer of pH 6.8 using dialysis bag diffusion technique. Particle sizes of all the formulations were in the range of 250 to 1406 nm, and the entrapment efficiency ranges from 55 to 66%. FTIR and DSC studies indicated no interaction between drug and lipid, and the XRD spectrum showed that RL-HCL is in amorphous form in the formulation. In vitro release profiles were biphasic in nature and followed Higuchi model of release kinetics. Pharmacokinetics of raloxifene loaded solid lipid nanoparticles after oral administration to Wistar rats was studied. Bioavailability of RL-HCL loaded SLN was nearly five times than that of pure RL-HCL.
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A comparison between use of spray and freeze drying techniques for preparation of solid self-microemulsifying formulation of valsartan and in vitro and in vivo evaluation.
Biomed Res Int
PUBLISHED: 04-10-2013
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The objective of the present study was to develop self micro emulsifying formulation (SMEF) of valsartan to improve its oral bioavailability. The formulations were screened on the basis of solubility, stability, emulsification efficiency, particle size and zeta potential. The optimized liquid SMEF contains valsartan (20% w/w), Capmul MCM C8 (16% w/w), Tween 80 (42.66% w/w) and PEG 400 (21.33% w/w) as drug, oil, surfactant and co-surfactant, respectively. Further, Liquid SMEF was adsorbed on Aerosol 200 by spray and freeze drying methods in the ratio of 2 : 1 and transformed into free flowing powder. Both the optimized liquid and solid SMEF had the particle size <200 nm with rapid reconstitution properties. Both drying methods are equally capable for producing stable solid SMEF and immediate release of drug in in vitro and in vivo conditions. However, the solid SMEF produced by spray drying method showed high flowability and compressibility. The solid state characterization employing the FTIR, DSC and XRD studies indicated insignificant interaction of drug with lipid and adsorbed excipient. The relative bioavailability of solid SMEF was approximately 1.5 to 3.0 folds higher than marketed formulation and pure drug. Thus, the developed solid SMEF illustrates an alternative delivery of valsartan as compared to existing formulations with improved bioavailability.
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Bioactive metabolites from an endophytic Cryptosporiopsis sp. inhabiting Clidemia hirta.
Phytochemistry
PUBLISHED: 03-16-2013
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An endophytic Cryptosporiopsis sp. was isolated from Clidemia hirta and analyzed for its secondary metabolites that lead to the isolation of three bioactive molecules. The compounds were purified from the culture broth of the fungus and their structures were determined by spectroscopic methods as (R)-5-hydroxy-2-methylchroman-4-one (1), 1-(2,6-dihydroxyphenyl)pentan-1-one (2) and (Z)-1-(2-(2-butyryl-3-hydroxyphenoxy)-6-hydroxyphenyl)-3-hydroxybut-2-en-1-one (3). Compound 1 exhibited significant cytotoxic activity against the human leukemia cell line, HL-60 with an IC50 of 4 ?g/ml. This compound induced G2 arrest of the HL-60 cell cycle significantly. In addition, out of these compounds, 2 and 3 were active against several bacterial pathogens. Compound 2 was active against Bacillus cereus, Escherichia coli and Staphylococcus aureus with IC50 values varying from 18 to 30 ?g/ml, and compound 3 displayed activity against Pseudomonas fluorescens with an IC50 value of 6 ?g/ml. Compounds 2 and 3 are novel whereas compound 1 was reported earlier but the stereochemistry of its C-2 methyl is established for the first time.
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Directed evolution of GH43 ?-xylosidase XylBH43 thermal stability and L186 saturation mutagenesis.
J. Ind. Microbiol. Biotechnol.
PUBLISHED: 03-12-2013
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Directed evolution of ?-xylosidase XylBH43 using a single round of gene shuffling identified three mutations, R45K, M69P, and L186Y, that affect thermal stability parameter K t (0.5) by -1.8 ± 0.1, 1.7 ± 0.3, and 3.2 ± 0.4 °C, respectively. In addition, a cluster of four mutations near hairpin loop-D83 improved K t (0.5) by ~3 °C; none of the individual amino acid changes measurably affect K t (0.5) . Saturation mutagenesis of L186 identified the variant L186K as having the most improved K t (0.5) value, by 8.1 ± 0.3 °C. The L186Y mutation was found to be additive, resulting in K t (0.5) increasing by up to 8.8 ± 0.3 °C when several beneficial mutations were combined. While k cat of xylobiose and 4-nitrophenyl-?-D-xylopyranoside were found to be depressed from 8 to 83 % in the thermally improved mutants, K m, K ss (substrate inhibition), and K i (product inhibition) values generally increased, resulting in lessened substrate and xylose inhibition.
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Insect bite reactions.
Indian J Dermatol Venereol Leprol
PUBLISHED: 02-28-2013
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Insects are a class of living creatures within the arthropods. Insect bite reactions are commonly seen in clinical practice. The present review touches upon the medically important insects and their places in the classification, the sparse literature on the epidemiology of insect bites in India, and different variables influencing the susceptibility of an individual to insect bites. Clinical features of mosquito bites, hypersensitivity to mosquito bites Epstein-Barr virus NK (HMB-EBV-NK) disease, eruptive pseudoangiomatosis, Skeeter syndrome, papular pruritic eruption of HIV/AIDS, and clinical features produced by bed bugs, Mexican chicken bugs, assassin bugs, kissing bugs, fleas, black flies, Blandford flies, louse flies, tsetse flies, midges, and thrips are discussed. Brief account is presented of the immunogenic components of mosquito and bed bug saliva. Papular urticaria is discussed including its epidemiology, the 5 stages of skin reaction, the SCRATCH principle as an aid in diagnosis, and the recent evidence supporting participation of types I, III, and IV hypersensitivity reactions in its causation is summarized. Recent developments in the treatment of pediculosis capitis including spinosad 0.9% suspension, benzyl alcohol 5% lotion, dimethicone 4% lotion, isopropyl myristate 50% rinse, and other suffocants are discussed within the context of evidence derived from randomized controlled trials and key findings of a recent systematic review. We also touch upon a non-chemical treatment of head lice and the ineffectiveness of egg-loosening products. Knockdown resistance (kdr) as the genetic mechanism making the lice nerves insensitive to permethrin is discussed along with the surprising contrary clinical evidence from Europe about efficacy of permethrin in children with head lice carrying kdr-like gene. The review also presents a brief account of insects as vectors of diseases and ends with discussion of prevention of insect bites and some serious adverse effects of mosquito coil smoke.
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Synthesis and in vitro evaluation of N-aryl pyrido-quinazolines derivatives as potent epidermal growth factor receptor inhibitors.
Chem Biol Drug Des
PUBLISHED: 02-16-2013
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A series of pyrido-quinazolines have been synthesised, characterized, and tested for their in vitro epidermal growth factor receptor (EGFR) tyrosine kinase inhibitory activity. The compounds were prepared from Alkylideno/arylideno-bis-ureas. Their final structure of the compounds was elucidated on the basis of spectral studies (IR, ¹H NMR, FT-IR, and EI-MS). The cellular EGFR internalization response of selected compounds was evaluated using HeLa cells. Most of the synthesized compounds displayed potent EGFR-TK inhibitory activity and structurally halogenated derivatives had a pronounced effect in inhibiting EGFR internalization.
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Neurogenetic disorders and treatment of associated seizures.
Pharmacotherapy
PUBLISHED: 02-11-2013
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Seizures are a frequent complication associated with several neurogenetic disorders. Antiepileptic medications remain the mainstay of treatment in these patients. We summarized the available data associated with various antiepileptic therapies used to treat patients with neurogenetic disorders who experienced recurrent seizures. A MEDLINE search was conducted to identify articles and abstracts describing the use of antiepileptic therapy for the treatment of various neurogenetic syndromes. Of all the neurogenetic syndromes, only autism spectrum disorders, Angelman syndrome, Rett syndrome, Dravet syndrome, and tuberous sclerosis complex were identified as having sufficient published information to evaluate therapy. Some efficacy trends were identified, including frequent successes with valproic acid with clonazepam for epilepsy with Angelman syndrome; valproic acid, stiripentol, and clobazam (triple combination therapy) for epilepsy with Dravet syndrome; and vigabatrin for infantile spasms associated with tuberous sclerosis complex. Due to a paucity of information regarding the mechanisms by which seizures are generated in the various disorders, approach to seizure control is primarily based on clinical experience and a limited amount of study data exploring patient outcomes. Although exposure of the developing brain to antiepileptic medications is of some concern, the control of epileptic activity is an important undertaking in these individuals, as the severity of eventual developmental delay often appears to correlate with the severity of seizures. As such, early aggressive therapy is warranted.
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Curcumin abates hypoxia-induced oxidative stress based-ER stress-mediated cell death in mouse hippocampal cells (HT22) by controlling Prdx6 and NF-?B regulation.
Am. J. Physiol., Cell Physiol.
PUBLISHED: 01-30-2013
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Oxidative stress and endoplasmic reticulum (ER) stress are emerging as crucial events in the etiopathology of many neurodegenerative diseases. While the neuroprotective contributions of the dietary compound curcumin has been recognized, the molecular mechanisms underlying curcumins neuroprotection under oxidative and ER stresses remains elusive. Herein, we show that curcumin protects HT22 from oxidative and ER stresses evoked by the hypoxia (1% O(2) or CoCl(2) treatment) by enhancing peroxiredoxin 6 (Prdx6) expression. Cells exposed to CoCl(2) displayed reduced expression of Prdx6 with higher reactive oxygen species (ROS) expression and activation of NF-?B with I?B phosphorylation. When NF-?B activity was blocked by using SN50, an inhibitor of NF-?B, or cells treated with curcumin, the repression of Prdx6 expression was restored, suggesting the involvement of NF-?B in modulating Prdx6 expression. These cells were enriched with an accumulation of ER stress proteins, C/EBP homologous protein (CHOP), GRP/78, and calreticulin, and had activated states of caspases 12, 9, and 3. Reinforced expression of Prdx6 in HT22 cells by curcumin reestablished survival signaling by reducing propagation of ROS and blunting ER stress signaling. Intriguingly, knockdown of Prdx6 by antisense revealed that loss of Prdx6 contributed to cell death by sustaining enhanced levels of ER stress-responsive proapoptotic proteins, which was due to elevated ROS production, suggesting that Prdx6 deficiency is a cause of initiation of ROS-mediated ER stress-induced apoptosis. We propose that using curcumin to reinforce the naturally occurring Prdx6 expression and attenuate ROS-based ER stress and NF-?B-mediated aberrant signaling improves cell survival and may provide an avenue to treat and/or postpone diseases associated with ROS or ER stress.
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Paenisporosarcina indica sp. nov., a psychrophilic bacterium from a glacier, and reclassification of Sporosarcina antarctica Yu et al., 2008 as Paenisporosarcina antarctica comb. nov. and emended description of the genus Paenisporosarcina.
Int. J. Syst. Evol. Microbiol.
PUBLISHED: 01-25-2013
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A Gram-stain-positive, aerobic, spore-forming, rod-shaped bacterium, PN2(T), was isolated from a soil sample collected near the Pindari glacier. It contained anteiso-C15 : 0, iso-C15 : 0 and C16 : 1?7c alcohol as the predominant fatty acids, MK-7 as the major menaquinone and A4? type (l-Lys-d-Glu) peptidoglycan. Based on these characteristics, strain PN2(T) was assigned to the genus Paenisporosarcina. Phylogenetic analysis based on 16S rRNA gene sequence placed strain PN2(T) within the genus Paenisporosarcina and showed a sequence similarity of 98.5-99.0 % with members of this genus. Paenisporosarcina macmurdoensis CMS 21w(T), Paenisporosarcina quisquiliarum SK 55(T) and Sporosarcina antarctica N-05(T) were identified as the most closely related species with 16S rRNA gene sequence similarities of 98.6 %, 99.0 % and 98.4 %, respectively. The values for DNA-DNA relatedness between strain PN2(T) and P. macmurdoensis, P. quisquiliarum and S. antarctica were below the 70 % threshold value (32.0 %, 42.0 % and 38.0 % respectively). In addition, strain PN2(T) exhibited a number of phenotypic differences from P. macmurdoensis, P. quisquiliarum and S. antarctica. Based on the cumulative differences, strain PN2(T) was identified as representing a novel species and the name Paenisporosarcina indica sp. nov. was proposed. The type strain of Paenisporosarcina indica sp. nov. is PN2(T) (LMG 23933(T) = JCM 15114(T)). Furthermore, based on the morphological and chemotaxonomic characteristics, the species Sporosarcina antarctica was reclassified as a species of the genus Paenisporosarcina and renamed Paenisporosarcina antarctica comb. nov. In addition, an emended description of the genus Paenisporosarcina is presented.
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Loss of p53 cooperates with K-ras activation to induce glioma formation in a region-independent manner.
Glia
PUBLISHED: 01-24-2013
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Gliomas are recognized as a heterogeneous group of neoplasms differing in their location and morphological features. These differences, between and within varying grades of gliomas, have not been explained solely on the grounds of an oncogenic stimulus. Interactions with the tumor microenvironment as well as inherent characteristics of the cell of origin are likely a source of this heterogeneity. There is an ongoing debate over the cell of origin of gliomas, where some suggest a progenitor, while others argue for a stem cell origin. Thus, it is presumed that neurogenic regions of the brain such as the subventricular zone (SVZ) containing large numbers of neural stem and progenitor populations are more susceptible to transformation. Our studies demonstrate that K-ras(G12D) cooperates with the loss of p53 to induce gliomas from both the SVZ and cortical region, suggesting that cells in the SVZ are not uniquely gliomagenic. Using combinations of doxycycline-inducible K-ras(G12D) and p53 loss, we show that tumors induced by the cooperative actions of these genes remain dependent on active K-ras expression, as deinduction of K-ras(G12D) leads to complete tumor regression despite absence of p53. These results suggest that the interplay between specific combinations of genetic alterations and susceptible cell types, rather than the site of origin, are important determinates of gliomagenesis. Additionally, this model supports the view that, although several genetic events may be necessary to confer traits associated with oncogenic transformation, inactivation of a single oncogenic partner can undermine tumor maintenance, leading to regression and disease remission.
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An analysis of biliary anatomy according to different classification systems.
Indian J Gastroenterol
PUBLISHED: 01-22-2013
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Variations in biliary anatomy are common, and different classifications have been described. These classification systems have not been compared to each other in a single cohort. We report such variations in biliary anatomy on magnetic resonance cholangiopancreatography (MRCP) using six different classification systems.
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Acne cosmetica revisited: a case-control study shows a dose-dependent inverse association between overall cosmetic use and post-adolescent acne.
Dermatology (Basel)
PUBLISHED: 01-21-2013
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Case-control studies to support the concept of acne cosmetica are lacking.
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Nanomaterials as Non-viral siRNA Delivery Agents for Cancer Therapy.
Bioimpacts
PUBLISHED: 01-14-2013
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Gene therapy has been recently shown as a promising tool for cancer treatment as nanotechnology-based safe and effective delivery methods are developed. Generally, genes are wrapped up in extremely tiny nanoparticles which could be taken up easily by cancer cells, not to their healthy neighboring cells. Several nanoparticle systems have been investigated primarily to address the problems involved in other methods of gene delivery and observed improved anticancer efficacy suggesting that nanomedicine provides novel opportunities to safely deliver genes, thus treat cancer. In this review, various nanoparticle types and related strategies, used in gene delivery for cancer treatment, have been discussed.
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Copolymers of poly(lactic acid) and D-?-tocopheryl polyethylene glycol 1000 succinate-based nanomedicines: versatile multifunctional platforms for cancer diagnosis and therapy.
Expert Opin Drug Deliv
PUBLISHED: 01-14-2013
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The major drawbacks associated with most of the anti-cancer drugs are their potential adverse effects. Distribution of these drugs throughout the body causes untoward adverse effects and less accumulation of drug at the site of tumors also causes decrease in therapeutic efficacy. Targeted nanomedicines are the emerging systems to improve the targetability of drug to the tumor site and to reduce the toxicity with maximum efficacy. Copolymers of poly-lactic acid (PLA) and D-?-tocopheryl polyethylene glycol 1000 succinate (Vitamin-E TPGS or TPGS) are innovative materials being actively investigated for the fabrication of non-targeted and targeted nanomedicines for diagnosis and therapy of cancer.
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Denaturing gradient gel electrophoresis profiling of bacterial communities composition in Arabian Sea.
J Environ Biol
PUBLISHED: 12-16-2011
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Denaturing gradient gel electrophoresis (DGGE) was used to elucidate spatial and temporal variations in bacterial community composition (BCC) from four locations along the central west coast of India. DNA extracts from 36 water samples collected from surface, mid-depth (-10 m) and dose to bottom (-20 m) during premonsoon, postmonsoon, monsoon were analyzed by PCRfor amplifying variable region of 16S rRNAgene and subsequently through DGGE. Prominent bands were excised, cloned and sequenced indicated the preponderance of gammaproteobacteria, bacteroidetes and cyanobacteria. Non-metric dimensional scaling of the DGGE gels indicated that the spatial variations in BCC were prominent among the sampling locations. Temporal variations in the BCC appear to be influenced by monsoonal processes. The canonical correspondence analyses suggest that the concentration of chlorophyll a and nitrate are two important environmental factors for both spatial and temporal variations in BCC. Chlorophyll a seems to be impart a top-down control of BCC while nitrate, the bottom-up control. Our results also suggest that BCC can vary over a small geographic distance in highly dynamic, seasonally predisposed tropical coastal waters.
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Exposing a hidden functional site of C-reactive protein by site-directed mutagenesis.
J. Biol. Chem.
PUBLISHED: 12-09-2011
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C-reactive protein (CRP) is a cyclic pentameric protein whose major binding specificity, at physiological pH, is for substances bearing exposed phosphocholine moieties. Another pentameric form of CRP, which exists at acidic pH, displays binding activity for oxidized LDL (ox-LDL). The ox-LDL-binding site in CRP, which is hidden at physiological pH, is exposed by acidic pH-induced structural changes in pentameric CRP. The aim of this study was to expose the hidden ox-LDL-binding site of CRP by site-directed mutagenesis and to generate a CRP mutant that can bind to ox-LDL without the requirement of acidic pH. Mutation of Glu(42), an amino acid that participates in intersubunit interactions in the CRP pentamer and is buried, to Gln resulted in a CRP mutant (E42Q) that showed significant binding activity for ox-LDL at physiological pH. For maximal binding to ox-LDL, E42Q CRP required a pH much less acidic than that required by wild-type CRP. At any given pH, E42Q CRP was more efficient than wild-type CRP in binding to ox-LDL. Like wild-type CRP, E42Q CRP remained pentameric at acidic pH. Also, E42Q CRP was more efficient than wild-type CRP in binding to several other deposited, conformationally altered proteins. The E42Q CRP mutant provides a tool to investigate the functions of CRP in defined animal models of inflammatory diseases including atherosclerosis because wild-type CRP requires acidic pH to bind to deposited, conformationally altered proteins, including ox-LDL, and available animal models may not have sufficient acidosis or other possible modifiers of the pentameric structure of CRP at the sites of inflammation.
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Noble-metal-free bimetallic nanoparticle-catalyzed selective hydrogen generation from hydrous hydrazine for chemical hydrogen storage.
J. Am. Chem. Soc.
PUBLISHED: 11-15-2011
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Noble-metal-free nickel-iron alloy nanoparticles exhibit excellent catalytic performance for the complete decomposition of hydrous hydrazine, for which the NiFe nanocatalyst, with equimolar compositions of Ni and Fe, shows 100% hydrogen selectivity in basic solution (0.5 M NaOH) at 343 K. The development of low-cost and high-performance catalysts may encourage the effective application of hydrous hydrazine as a promising hydrogen storage material.
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Comparative study of 2 palatoplasty techniques to assess speech and fistula in primary cleft palate patients.
J Dent Child (Chic)
PUBLISHED: 11-02-2011
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To assess the Quality of speech and the incidence of post operative fistula in each technique after 6 months follow up study.
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The transcription factor CrWRKY1 positively regulates the terpenoid indole alkaloid biosynthesis in Catharanthus roseus.
Plant Physiol.
PUBLISHED: 10-11-2011
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Catharanthus roseus produces a large array of terpenoid indole alkaloids (TIAs) that are an important source of natural or semisynthetic anticancer drugs. The biosynthesis of TIAs is tissue specific and induced by certain phytohormones and fungal elicitors, indicating the involvement of a complex transcriptional control network. However, the transcriptional regulation of the TIA pathway is poorly understood. Here, we describe a C. roseus WRKY transcription factor, CrWRKY1, that is preferentially expressed in roots and induced by the phytohormones jasmonate, gibberellic acid, and ethylene. The overexpression of CrWRKY1 in C. roseus hairy roots up-regulated several key TIA pathway genes, especially Tryptophan Decarboxylase (TDC), as well as the transcriptional repressors ZCT1 (for zinc-finger C. roseus transcription factor 1), ZCT2, and ZCT3. However, CrWRKY1 overexpression repressed the transcriptional activators ORCA2, ORCA3, and CrMYC2. Overexpression of a dominant-repressive form of CrWRKY1, created by fusing the SRDX repressor domain to CrWRKY1, resulted in the down-regulation of TDC and ZCTs but the up-regulation of ORCA3 and CrMYC2. CrWRKY1 bound to the W box elements of the TDC promoter in electrophoretic mobility shift, yeast one-hybrid, and C. roseus protoplast assays. Up-regulation of TDC increased TDC activity, tryptamine concentration, and resistance to 4-methyl tryptophan inhibition of CrWRKY1 hairy roots. Compared with control roots, CrWRKY1 hairy roots accumulated up to 3-fold higher levels of serpentine. The preferential expression of CrWRKY1 in roots and its interaction with transcription factors including ORCA3, CrMYC2, and ZCTs may play a key role in determining the root-specific accumulation of serpentine in C. roseus plants.
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High energy resolution bandpass photon detector for inverse photoemission spectroscopy.
Rev Sci Instrum
PUBLISHED: 10-07-2011
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We report a bandpass ultraviolet photon detector for inverse photoemission spectroscopy with energy resolution of 82 ± 2 meV. The detector (Sr(0.7)Ca(0.3)F(2)/acetone) consists of Sr(0.7)Ca(0.3)F(2) entrance window with energy transmission cutoff of 9.85 eV and acetone as detection gas with 9.7 eV photoionization threshold. The response function of the detector, measured using synchrotron radiation, has a nearly Gaussian shape. The n = 1 image potential state of Cu(100) and the Fermi edge of silver have been measured to demonstrate the improvement in resolution compared to the CaF(2)/acetone detector. To show the advantage of improved resolution of the Sr(0.7)Ca(0.3)F(2)/acetone detector, the metal to semiconductor transition in Sn has been studied. The pseudogap in the semiconducting phase of Sn could be identified, which is not possible with the CaF(2)/acetone detector because of its worse resolution.
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Comparative one-factor-at-a-time, response surface (statistical) and bench-scale bioreactor level optimization of thermoalkaline protease production from a psychrotrophic Pseudomonas putida SKG-1 isolate.
Microb. Cell Fact.
PUBLISHED: 10-04-2011
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Production of alkaline protease from various bacterial strains using statistical methods is customary now-a-days. The present work is first attempt for the production optimization of a solvent stable thermoalkaline protease by a psychrotrophic Pseudomonas putida isolate using conventional, response surface methods, and fermentor level optimization.
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Radiogenomic mapping of edema/cellular invasion MRI-phenotypes in glioblastoma multiforme.
PLoS ONE
PUBLISHED: 07-18-2011
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Despite recent discoveries of new molecular targets and pathways, the search for an effective therapy for Glioblastoma Multiforme (GBM) continues. A newly emerged field, radiogenomics, links gene expression profiles with MRI phenotypes. MRI-FLAIR is a noninvasive diagnostic modality and was previously found to correlate with cellular invasion in GBM. Thus, our radiogenomic screen has the potential to reveal novel molecular determinants of invasion. Here, we present the first comprehensive radiogenomic analysis using quantitative MRI volumetrics and large-scale gene- and microRNA expression profiling in GBM.
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Synthetic triterpenoid cyano enone of methyl boswellate activates intrinsic, extrinsic, and endoplasmic reticulum stress cell death pathways in tumor cell lines.
Mol. Cancer Ther.
PUBLISHED: 07-11-2011
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We explored the effect of a novel synthetic triterpenoid compound cyano enone of methyl boswellates (CEMB) on various prostate cancer and glioma cancer cell lines. CEMB displayed concentration-dependent cytotoxic activity with submicromolar lethal dose 50% (LD(50)) values in 10 of 10 tumor cell lines tested. CEMB-induced cytotoxicity is accompanied by activation of downstream effector caspases (caspases 3 and 7) and by upstream initiator caspases involved in both the extrinsic (caspase 8) and intrinsic (caspase 9) apoptotic pathways. By using short interfering RNAs (siRNA), we show evidence that knockdown of caspase 8, DR4, Apaf-1, and Bid impairs CEMB-induced cell death. Similar to other proapoptotic synthetic triterpenoid compounds, CEMB-induced apoptosis involved endoplasmic reticulum stress, as shown by partial rescue of tumor cells by siRNA-mediated knockdown of expression of genes involved in the unfolded protein response such as IRE1?, PERK, and ATF6. Altogether, our results suggest that CEMB stimulates several apoptotic pathways in cancer cells, suggesting that this compound should be evaluated further as a potential agent for cancer therapy.
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Evidence-based treatments for pemphigus vulgaris, pemphigus foliaceus, and bullous pemphigoid: a systematic review.
Indian J Dermatol Venereol Leprol
PUBLISHED: 07-06-2011
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Pemphigus, bullous pemphigoid, and epidermolysis bullosa acquisita are autoimmune diseases of skin associated with considerable morbidity and sometimes mortality. There is no cure for these diseases. Aims: To summarize evidence-based treatments for these diseases by performing a systematic review.
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Formulation of topical bioadhesive gel of aceclofenac using 3-level factorial design.
Iran J Pharm Res
PUBLISHED: 07-01-2011
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The objective of this work was to develop bioadhesive topical gel of Aceclofenac with the help of response-surface approach. Experiments were performed according to a 3-level factorial design to evaluate the effects of two independent variables [amount of Poloxamer 407 (PL-407 = X1) and hydroxypropylmethyl cellulose K100 M (HPMC = X2)] on the bioadhesive character of gel, rheological property of gel (consistency index), and in-vitro drug release. The best model was selected to fit the data. Mathematical equation was generated by Design Expert® software for the model which assists in determining the effect of independent variables. Response surface plots were also generated by the software for analyzing effect of the independent variables on the response. Quadratic model was found to be the best for all the responses. Both independent variable (X1 and X2) were found to have synergistic effect on bioadhesion (Y1) but the effect of HPMC was more pronounced than PL-407. Consistency index was enhanced by increasing the level of both independent variables. An antagonistic effect of both independent variables was found on cumulative percentage release of drug in 2 (Y3) and 8 h (Y4). Both independent variables approximately equally contributed the antagonistic effect on Y3 whereas antagonistic effect of HPMC was more pronounced than PL-407. The effect of formulation variables on the product characteristics can be easily predicted and precisely interpreted by using a 3-level factorial experimental design and generated quadratic mathematical equations.
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Investigations on gastroprotective effect of citalopram, an antidepressant drug against stress and pyloric ligation induced ulcers.
Pharmacol Rep
PUBLISHED: 06-28-2011
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The present study investigates the gastroprotective effect of citalopram, an antidepressant drug. Gastroprotective activity of citalopram (5, 10 and 20 mg/kg, bid, po) was evaluated both by single and 14 days repeated pretreatment in the cold restraint stress (CRS) model and 14 days repeated pretreatment in pyloric ligation (PL) model. In addition to ulcer scoring and its histological assessment, levels of corticosterone, hexosamine, nitrite, PGE(2), lipid peroxide and microvascular permeability were also estimated. Mechanism underlying gastroprotective activity was further explored by investigating the involvement of nitric oxide (NO), sulfhydryl (SH) compounds, ATP-sensitive K(+) channels (K(ATP) channels) and prostaglandins (PGs). Results show that against CRS model, repeated pretreatment with citalopram exhibit a significant gastroprotective effect while single pretreatment was ineffective. In CRS model, citalopram repeated pretreatment, in contrast to its single pretreatment, attenuates the corticosterone level and also mitigates the stress-induced increase in nitrite level, lipid peroxidation and microvascular permeability. Additionally, the repeated pretreatment increases the hexosamine and PGE(2) level in CRS model. This gastroprotective effect of citalopram was found to be decreased with L-NAME, NEM, glibenclamide and indomethacin pretreatment. Thus, gastroprotective activity of citalopram appears to be mediated by endogenous NO, SH, PGs and K(ATP) channel opening. In contrast to CRS model, repeated pretreatment with citalopram was ineffective in reducing ulcer formation in PL model.
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Growth inhibitory, apoptotic and anti-inflammatory activities displayed by a novel modified triterpenoid, cyano enone of methyl boswellates.
J. Biosci.
PUBLISHED: 06-10-2011
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Triterpenoids are pentacyclic secondary metabolites present in many terrestrial plants. Natural triterpenoids have been reported to exhibit anti-inflammatory and anti-carcinogenic activities. Here, we show that modifications of ring A of boswellic acid (2 cyano, 3 enone) resulted in a highly active growth inhibitory, anti-inflammatory, prodifferentiative and anti-tumour triterpenoid compound called cyano enone of methyl boswellates (CEMB). This compound showed cytotoxic activity on a number of cancer cell lines with IC?? ranging from 0.2 to 0.6 ?M. CEMB inhibits DNA synthesis and induces apoptosis in A549 cell line at 0.25 ?M and 1 ?M concentrations, respectively. CEMB induces adipogenic differentiation in 3T3-L1 cells at a concentration of 0.1 ?M. Finally, administration of CEMB intra-tumourally significantly inhibited the growth of C6 glioma tumour xenograft in immuno-compromised mice. Collectively, these results suggest that CEMB is a very potent anti-tumour compound.
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