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1.
Br Dent J ; 234(12): 843, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37349414
2.
Br Dent J ; 234(8): 556, 2023 04.
Article in English | MEDLINE | ID: mdl-37117337
3.
Br Dent J ; 234(4): 197, 2023 02.
Article in English | MEDLINE | ID: mdl-36828996
4.
Sci Rep ; 11(1): 14692, 2021 07 19.
Article in English | MEDLINE | ID: mdl-34282191

ABSTRACT

The study is of great relevance with present day pandemic era where mushrooms have immunity enhancing properties and they convert agro-wastes into protein rich food. India is having a youth population of about 750 million and mushroom cultivation has good potential to contribute in national income as well as enhanced immunity. The key aspects undertaken during research were the spawn production, cultivation methodology, and the suitability of various factors affecting the production and yield attributes of Pleurotus eryngii under ambient conditions in subtropical areas. Study includes yield enhancing substrate, sterilization method, spawn and substrate quantity in the growing of King Oyster i.e. Pleurotus eryngii in subtropical zones. Paddy straw was found to be the best substrate giving the highest biological efficiency and producing maximum number of fruiting bodies which is otherwise burnt by farmers in India and it is a major cause of air pollution. Whereas, maize straw showed fastest spawn run and pin head emergence out of six tested substrates and supplements. But, due to the unavailability of paddy straw in this region, the other straws resulting in optimum yields are to be recommended. Chemical steeping of substrate with chlorine water at 0.4% + carbendazim at 2% + dichlorovos at 0.1% of water used for soaking showed best results in terms of biological efficiency whereas, water and aerated steam treatment of substrate at 85 °C-90°C for about 60-90 min supported the results in leaching of nutrients and thus, biological efficiency gets lower. Out of four spawn rates used, spawn rate of 5% was found significantly best resulting in maximum biological efficiency, fastest mycelial run, primordial initiation and highest average fruit body weight. All the experiments were found statistically significant except the experiment that was performed for evaluating the optimum quantity of substrate for bag preparation. There was not much difference in the obtained yields with respect to increase in the amounts of substrate. So, growing this mushroom from the obtained best results will result in better production with higher income even for the marginal farmers in subtropical zones of world.

5.
Neurochem Int ; 139: 104783, 2020 10.
Article in English | MEDLINE | ID: mdl-32652268

ABSTRACT

Transient receptor potential (TRP) channels are Ca2+ permeable non-selective cation channels which play a pivotal role in diabetes and diabetic complications. Among diabetic complications, diabetes-induced cognitive impairment is a major CNS complication. The role of several TRP channels has been investigated extensively for their diverse Ca2+ regulating mechanism, and recently their role has been postulated in the progression of neurodegenerative disorders. However, the role of TRPV2 has not been investigated yet. Therefore, in the present study, the involvement of TRPV2 channels was investigated in diabetes-induced cognitive impairment using TRPV2 inhibitor, tranilast. High glucose exposure in rat C6 glial cells enhances the Ca2+-entry through TRPV2 channels. In our in-vivo study, diabetic rats showed increased gene and protein expression of TRPV2 in the hippocampus. Subsequent increase in the acetylcholinesterase activity in the cortex, as well as decrease in the phosphorylation of Ca2+/calmodulin-dependent protein kinase II (p-CaMKII-Thr-286), p-GSK-3ß (Ser-9), p-CREB (Ser-133) and postsynaptic density protein 95 (PSD-95) in the hippocampus were also observed this led to the impairment in the learning and memory as evident from behavioral parameters such as Morris water maze test, passive avoidance and Y-maze test paradigm. Three-week treatment with tranilast (30 and 100 mg/kg, p.o.) showed improvement in learning and memory associated behaviours (Morris water maze test, passive avoidance, and Y-maze test) by increasing the p-CaMKII (Thr-286), p-GSK-3ß (Ser-9), p-CREB (Ser-133) and PSD-95 in the hippocampus. Cortical acetylcholinesterase activity was also reduced by the tranilast. These findings depicted that TRPV2 inhibition may be an effective treatment strategy in diabetes-induced cognitive deficits.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Cognitive Dysfunction/drug therapy , Diabetes Mellitus, Experimental/drug therapy , TRPV Cation Channels/antagonists & inhibitors , ortho-Aminobenzoates/therapeutic use , Animals , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Cells, Cultured , Cognitive Dysfunction/etiology , Cognitive Dysfunction/metabolism , Diabetes Mellitus, Experimental/complications , Diabetes Mellitus, Experimental/metabolism , Dose-Response Relationship, Drug , Male , Maze Learning/drug effects , Maze Learning/physiology , Rats , Rats, Sprague-Dawley , TRPV Cation Channels/metabolism , ortho-Aminobenzoates/pharmacology
6.
Int J Biol Macromol ; 127: 126-135, 2019 Apr 15.
Article in English | MEDLINE | ID: mdl-30610949

ABSTRACT

Zinc deficient/or alkaline soil is globally widespread issue and cultivation of cereals in such soil results in severe depression in plant growth, higher disease incidence and lower grain yield. To address such problems, laboratory synthesized Zn-chitosan nanoparticles (NPs) were evaluated via seed priming and foliar application in maize plants. Zn-chitosan NPs (0.01-0.16%) showed strong in vitro antifungal and seedling growth promotry activities. Further, Zn-chitosan NPs exhibited significant disease control through strengthening of plant innate immunity by elevating antioxidant and defense enzymes, balancing of reactive oxygen species (ROS) and enhancing lignin accumulation. In field, seed treatment and foliar application of developed NPs (0.01-0.16%) significantly controlled Curvularia leaf spot (CLS) disease, increased grain yield from 20.5 to 39.8% and enriched the grain with zinc micronutrient from 41.27 to 62.21 µg/g dw. Results claim that Zn-chitosan NPs could be an effective growth promotry, disease controlling and micronutrient fortifying agent in maize crop.


Subject(s)
Chitosan , Nanoparticles/chemistry , Plant Diseases , Plant Immunity/drug effects , Zea mays , Zinc , Chitosan/chemistry , Chitosan/pharmacology , Crop Production , Plant Diseases/immunology , Plant Diseases/microbiology , Zea mays/growth & development , Zea mays/immunology , Zea mays/microbiology , Zinc/chemistry , Zinc/pharmacology
7.
Int J Biol Macromol ; 123: 59-69, 2019 Feb 15.
Article in English | MEDLINE | ID: mdl-30389525

ABSTRACT

In this work, salicylic acid-chitosan nanoparticles (SA-CS NPs) are reported as a biostimulant for promoting plant defense and growth in maize. SA-CS NPs were characterised for colloidal size distribution, functional group, surface chemistry, chemical composition, crystal structure and morphology. Investigation discloses a method of SA-CS NPs synthesis, release profile of SA from SA-CS NPs, antifungal and seedling growth promoting activities. Findings unveil that SA-CS NPs expressed significant physiological-biochemical responses in vitro and in vivo. The responses were recorded as elevated antioxidant-defense enzyme activities, balancing reactive oxygen species (ROS), cell wall reinforcement by lignin deposition, disease control and plant growth in maize. In field, 59.4% control of post-flowering stalk rot (PFSR) disease and 57.8% yield enhancement was evident in SA-CS NPs application compared to SA treatment. The obtained results claim commercial potential of SA-CS NPs as a biostimulant for plant disease control and higher yield.


Subject(s)
Chitosan/chemistry , Nanoparticles/chemistry , Plant Diseases/prevention & control , Salicylic Acid/chemistry , Zea mays/drug effects , Antifungal Agents/chemistry , Antifungal Agents/pharmacology , Antioxidants/pharmacology , Cell Survival/drug effects , Particle Size , Reactive Oxygen Species/metabolism , Seedlings/drug effects
8.
Nanoscale Res Lett ; 13(1): 381, 2018 Nov 28.
Article in English | MEDLINE | ID: mdl-30488132

ABSTRACT

Dye-sensitized solar cells (DSSCs) belong to the group of thin-film solar cells which have been under extensive research for more than two decades due to their low cost, simple preparation methodology, low toxicity and ease of production. Still, there is lot of scope for the replacement of current DSSC materials due to their high cost, less abundance, and long-term stability. The efficiency of existing DSSCs reaches up to 12%, using Ru(II) dyes by optimizing material and structural properties which is still less than the efficiency offered by first- and second-generation solar cells, i.e., other thin-film solar cells and Si-based solar cells which offer ~ 20-30% efficiency. This article provides an in-depth review on DSSC construction, operating principle, key problems (low efficiency, low scalability, and low stability), prospective efficient materials, and finally a brief insight to commercialization.

9.
Sci Rep ; 8(1): 6650, 2018 04 27.
Article in English | MEDLINE | ID: mdl-29703904

ABSTRACT

An antibacterial and plant growth promoting nanoemulsion was formulated using thymol, an essential oil component of plant and Quillaja saponin, a glycoside surfactant of Quillaja tree. The emulsion was prepared by a sonication method. Fifty minutes of sonication delivered a long term stable thymol nanoemulsion which was characterized by dynamic light scattering (DLS), transmission electron microscopy (TEM), cryogenic-field emission scanning electron microscopy (Cryo-FESEM) and fourier transform infra-red (FTIR) spectroscopy. Creaming index, pH and dilution stability were also studied for deliberation of its practical applications. The nanoemulsion (0.01-0.06%, v/v) showed substantial in vitro growth inhibition of Xanthomonas axonopodis pv. glycine of soybean (6.7-0.0 log CFU/ml). In pot experiments, seed treatment and foliar application of the nanoemulsion (0.03-0.06%, v/v) significantly lowered the disease severity (DS) (33.3-3.3%) and increased percent efficacy of disease control (PEDC) (54.9-95.4%) of bacterial pustule in soybean caused by X. axonopodis pv. glycine. Subsequently, significant enhancements of plant growth were also recorded in plants treated with thymol nanoemulsion. This is the first report of a thymol based nanoemulsion obtained using Quillaja saponin as a surfactant. Our study claims that nano scale thymol could be a potential antimicrobial and plant growth promoting agent for agriculture.


Subject(s)
Anti-Infective Agents, Local/pharmacology , Emulsions/pharmacology , Glycine max/growth & development , Plant Diseases/microbiology , Plant Growth Regulators/pharmacology , Thymol/pharmacology , Xanthomonas axonopodis/drug effects , Anti-Infective Agents, Local/chemistry , Anti-Infective Agents, Local/isolation & purification , Dynamic Light Scattering , Emulsions/chemistry , Microscopy, Electron, Scanning , Microscopy, Electron, Transmission , Oils, Volatile/chemistry , Plant Growth Regulators/chemistry , Plant Growth Regulators/isolation & purification , Quillaja/chemistry , Sonication , Glycine max/drug effects , Spectroscopy, Fourier Transform Infrared , Thymol/chemistry , Thymol/isolation & purification
10.
Sci Rep ; 7(1): 9754, 2017 08 29.
Article in English | MEDLINE | ID: mdl-28851884

ABSTRACT

In agriculture, search for biopolymer derived materials are in high demand to replace the synthetic agrochemicals. In the present investigation, the efficacy of Cu-chitosan nanoparticles (NPs) to boost defense responses against Curvularia leaf spot (CLS) disease of maize and plant growth promotry activity were evaluated. Cu-chitosan NPs treated plants showed significant defense response through higher activities of antioxidant (superoxide dismutase and peroxidase) and defense enzymes (polyphenol oxidase and phenylalanine ammonia-lyase). Significant control of CLS disease of maize was recorded at 0.04 to 0.16% of Cu-chitosan NPs treatments in pot and 0.12 to 0.16% of NPs treatments in field condition. Further, NPs treatments exhibited growth promotry effect in terms of plant height, stem diameter, root length, root number and chlorophyll content in pot experiments. In field experiment, plant height, ear length, ear weight/plot, grain yield/plot and 100 grain weight were enhanced in NPs treatments. Disease control and enhancement of plant growth was further enlightened through Cu release profile of Cu-chitosan NPs. This is an important development in agriculture nanomaterial research where biodegradable Cu-chitosan NPs are better compatible with biological control as NPs "mimic" the natural elicitation of the plant defense and antioxidant system for disease protection and sustainable growth.


Subject(s)
Chitosan/metabolism , Copper/metabolism , Nanoparticles/metabolism , Plant Growth Regulators/metabolism , Plant Immunity/drug effects , Zea mays/drug effects , Zea mays/growth & development , Plant Diseases/prevention & control , Zea mays/immunology
11.
Indian J Cancer ; 54(2): 439-441, 2017.
Article in English | MEDLINE | ID: mdl-29469074

ABSTRACT

AIMS: : To compare perioperative complications in esophagectomy after neoadjuvant therapy v/s primary surgery. SETTINGS AND DESIGN: : Retrospective analysis of perioperative complications in a prospectively maintained data base of patients who underwent esophagectomy as Primary surgery or after neoadjuvant therapy was done. METHODS AND MATERIAL: : 238 cases of esophagectomies performed for esophageal carcinoma were analysed and compared, out of which 125(52.5%) were given neoadjuvant therapy followed by surgery and 113(47.5%) underwent primary surgery. Surgical procedure was standard for both the groups. All the cases were analysed for perioperative complications. STATISTICAL ANALYSIS USED: : Data was analysed using Open Epi soft ware. Association between the two study group was assessed with Chi square test. RESULTS: : On comparison, both the groups were comparable in demographic profile and type of surgery performed. However, tumour stage was higher for cases who received neoadjuvant therapy as expected. On analysis there was no significant difference in overall morbidity and 30 days mortality. CONCLUSIONS: : Neoadjuvant Chemo/chemoradiotherapy is a feasible option in esophageal carcinoma without increase in incidence of peri operative morbidity or mortality.


Subject(s)
Esophagectomy/methods , Perioperative Period/adverse effects , Female , Humans , Male , Middle Aged , Neoadjuvant Therapy , Prospective Studies , Retrospective Studies , Treatment Outcome
12.
Neuroscience ; 305: 183-96, 2015 Oct 01.
Article in English | MEDLINE | ID: mdl-26255676

ABSTRACT

Glucose uptake in neurons depends on their cellular/physiological activity and the extracellular concentration of glucose around the cell. High concentration of extra-cellular glucose, as under hyperglycemic conditions or pathological condition in diabetes, may persist for extended periods of time in neurons and trigger cellular damage by altering voltage-gated sodium channels (VGSCs), the exact mechanism of which remains unclear. Therefore, we hypothesized that high glucose may directly affect kinetics of the VGSCs in the dorsal root ganglion (DRG) neurons. DRG neurons were exposed to normal glucose (NG: 5.5 mM) and high glucose (HG: 30 mM) for 24 h. In another set of experiments, diabetic DRG neurons were also isolated from streptozotocin-induced diabetic rats. Effects of sodium channel blockers on nociceptive parameters and tetrodotoxin-resistant (TTX-R) Na(+) channel kinetics were elucidated by whole-cell patch-clamp in HG exposure and diabetes-induced rat DRG neurons. HG exposure and diabetes-induced DRG neurons demonstrated significant increase in TTX-R Na(+) current (INa) densities in comparison to the control. Both HG-exposed and diabetic DRG neurons demonstrated similar biophysical characteristics of INa. Lidocaine and tetracaine significantly decreased TTX-R INa density in a concentration- and voltage-dependent manner. Steady-state fast inactivation of INa was shifted in the hyperpolarizing direction whereas voltage-dependent activation was shifted in the rightward direction. Diabetic rats treated with lidocaine and tetracaine (3 mg/kg, i.p.) significantly improved thermal hyperalgesia, mechanical allodynia and motor nerve conduction velocity with a significant inhibition of TTX-R INa density as compared to the diabetic control. These results suggest that HG exposure increases the TTX-R Na(+) channel activity sensitive to Na(+) channel blockers, lidocaine and tetracaine.


Subject(s)
Diabetes Mellitus, Experimental/drug therapy , Glucose/therapeutic use , Sodium Channel Blockers/pharmacology , Sweetening Agents/therapeutic use , Tetrodotoxin/pharmacology , Voltage-Gated Sodium Channels/metabolism , Animals , Antibiotics, Antineoplastic/toxicity , Cells, Cultured , Diabetes Mellitus, Experimental/chemically induced , Disease Models, Animal , Drug Interactions , Ganglia, Spinal/cytology , Lidocaine/therapeutic use , Male , Membrane Potentials/drug effects , Neurons/drug effects , Neurons/physiology , Patch-Clamp Techniques , Rats , Rats, Sprague-Dawley , Streptozocin/toxicity
13.
Int J Biol Macromol ; 75: 346-53, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25617841

ABSTRACT

Cu-chitosan nanoparticles were synthesized and evaluated for their growth promotory and antifungal efficacy in tomato (Solanum lycopersicum Mill). Physico-chemical characterization of the developed Cu-chitosan nanoparticles was carried out by DLS, FTIR, TEM, SEM-EDS and AAS. The study highlighted the stability and porous nature of Cu-chitosan nanoparticles. Laboratory synthesized nanoparticles showed substantial growth promotory effect on tomato seed germination, seedling length, fresh and dry weight at 0.08, 0.10 and 0.12% level. At 0.12% concentration these nanoparticles caused 70.5 and 73.5% inhibition of mycelia growth and 61.5 and 83.0% inhibition of spore germination in Alternaria solani and Fusarium oxysporum, respectively, in an in vitro model. In pot experiments, 0.12% concentration of Cu-chitosan nanoparticles was found most effective in percentage efficacy of disease control (PEDC) in tomato plants with the values of 87.7% in early blight and 61.1% in Fusarium wilt. The overall results confirm the significant growth promotory as well as antifungal capabilities of Cu-chitosan nanoparticles. Our model demonstrated the synthesis of Cu-chitosan nanoparticles and open up the possibility to use against fungal disease at field level. Further, developed porous nanomaterials could be exploited for delivery of agrochemicals.


Subject(s)
Antifungal Agents/pharmacology , Chitosan/chemical synthesis , Chitosan/pharmacology , Copper/pharmacology , Nanoparticles/chemistry , Plant Diseases/microbiology , Solanum lycopersicum/microbiology , Dynamic Light Scattering , Fusarium/drug effects , Solanum lycopersicum/drug effects , Microbial Sensitivity Tests , Models, Biological , Mycelium/drug effects , Mycelium/growth & development , Nanoparticles/ultrastructure , Porosity , Seedlings/drug effects , Seedlings/growth & development , Spectrometry, X-Ray Emission , Spectroscopy, Fourier Transform Infrared , Spores, Fungal/drug effects , Spores, Fungal/growth & development
14.
Curr Med Chem ; 20(36): 4640-5, 2013.
Article in English | MEDLINE | ID: mdl-24206125

ABSTRACT

Resveratrol is a naturally occurring phytoalexin found in many plants, nuts and fruits and is abundant in grapes and red wine. Resveratrol possesses a wide range of biological activities which include antioxidant, anti-inflammatory, chemoprotective, chemopreventive etc. Resveratrol has been investigated extensively in diabetes and its complications which suggest its anti-diabetic activity and protective effect against various diabetic complications. Neurons are extremely susceptible to oxidant-induced damage which may be due to their high rate of oxygen consumption and low levels of antioxidant defence enzymes. Traditionally, it was thought that the protective actions of resveratrol in diabetic neuropathy are due to its intrinsic radical scavenger properties. However, recently many other associated or separate mechanisms like upregulation of Nrf2, SIRT1 and inhibition of NF-κB, AP-1 have been proposed for its beneficial effect against nerve dysfunction. This present review discusses the neuroprotective effects of resveratrol that have been observed in experimental diabetic neuropathy and possible mechanistic explanations, as these effects may provide directions for the development of newer therapies. Futuristic therapies can be based on either resveratrol or its analogs with better bioavailability, or combining the resveratrol with existing therapies.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Diabetic Neuropathies/drug therapy , Neuroprotective Agents/pharmacology , Stilbenes/pharmacology , Animals , Humans , Resveratrol
15.
Int J Biol Macromol ; 62: 677-83, 2013 Nov.
Article in English | MEDLINE | ID: mdl-24141067

ABSTRACT

The main aim of present study was to prepare chitosan, chitosan-saponin and Cu-chitosan nanoparticles to evaluate their in vitro antifungal activities. Various nanoparticles were prepared using ionic gelation method by interaction of chitosan, sodium tripolyphosphate, saponin and Cu ions. Their particle size, polydispersity index, zeta potential and structures were confirmed by DLS, FTIR, TEM and SEM. The antifungal properties of nanoparticles against phytopathogenic fungi namely Alternaria alternata, Macrophomina phaseolina and Rhizoctonia solani were investigated at various concentrations ranging from 0.001 to 0.1%. Among the various formulations of nanoparticles, Cu-chitosan nanoparticles were found most effective at 0.1% concentration and showed 89.5, 63.0 and 60.1% growth inhibition of A. alternata, M. phaseolina and R. solani, respectively in in vitro model. At the same concentration, Cu-chitosan nanoparticles also showed maximum of 87.4% inhibition rate of spore germination of A. alternata. Chitosan nanoparticles showed the maximum growth inhibitory effects (87.6%) on in vitro mycelial growth of M. phaseolina at 0.1% concentration. From our study it is evident that chitosan based nanoparticles particularly chitosan and Cu-chitosan nanoparticles have tremendous potential for further field screening towards crop protection.


Subject(s)
Antifungal Agents/chemistry , Chitosan/chemistry , Nanoparticles/chemistry , Antifungal Agents/pharmacology , Chitosan/pharmacology , Copper/chemistry , Disk Diffusion Antimicrobial Tests , Fungi/drug effects , Nanoparticles/ultrastructure , Particle Size , Saponins/chemistry , Spectroscopy, Fourier Transform Infrared
16.
Cell Death Dis ; 4: e566, 2013 Mar 28.
Article in English | MEDLINE | ID: mdl-23538447

ABSTRACT

Osteosarcoma (OS) is an aggressive bone cancer typically observed in adolescents and young adults. Metastatic relapse accounts primarily for treatment failure, and obstacles to improving cure rates include a lack of efficacious agents. Our studies show apoptosis of OS cells prepared from localized and metastatic tumors by a novel drug combination: SCH727965 (SCH), a cyclin-dependent kinase inhibitor, and NVP-AUY922 (AUY) or other heat shock protein 90 inhibitor. SCH and AUY induced apoptosis when added simultaneously to cells and when AUY was added to and removed from cells before SCH addition. Sequential treatment was most effective when cells received AUY for ~12 h and when SCH was presented to cells immediately after AUY removal. The apoptotic protein Bax accumulated in mitochondria of cotreated cells but was primarily cytosolic in cells receiving either agent alone. Additional data show that SCH and AUY cooperatively induce the apoptosis of other sarcoma cell types but not of normal osteoblasts or fibroblasts, and that SCH and AUY individually inhibit cell cycle progression throughout the cell cycle. We suggest that the combination of SCH and AUY may be an effective new strategy for treatment of OS.


Subject(s)
Bridged Bicyclo Compounds, Heterocyclic/pharmacology , Cyclin-Dependent Kinases/antagonists & inhibitors , Gene Expression Regulation, Neoplastic/drug effects , HSP90 Heat-Shock Proteins/antagonists & inhibitors , Isoxazoles/pharmacology , Protein Kinase Inhibitors/pharmacology , Pyridinium Compounds/pharmacology , Resorcinols/pharmacology , Apoptosis/drug effects , Apoptosis/genetics , Bone Neoplasms/drug therapy , Cell Cycle/drug effects , Cell Cycle/genetics , Cell Line, Tumor , Cyclic N-Oxides , Cyclin-Dependent Kinases/genetics , Cyclin-Dependent Kinases/metabolism , Cytosol/drug effects , Cytosol/metabolism , Drug Synergism , HSP90 Heat-Shock Proteins/genetics , HSP90 Heat-Shock Proteins/metabolism , Humans , Indolizines , Mitochondria/drug effects , Mitochondria/metabolism , Osteosarcoma/drug therapy , Protein Transport , Signal Transduction/drug effects , bcl-2-Associated X Protein/genetics , bcl-2-Associated X Protein/metabolism
17.
Neuroscience ; 232: 64-73, 2013 Mar 01.
Article in English | MEDLINE | ID: mdl-23262239

ABSTRACT

Neuropathy is often seen in uncontrolled diabetes and the mechanisms involved for neuropathic pain are poorly understood. Hyperglycemia is a consequence of chronic uncontrolled diabetes and it is postulated to produce neuropathic pain. Therefore, in this study, we have investigated the effects of hyperglycemia on Na(+) channel kinetics in cultured dorsal root ganglion (DRG) neurons from neonatal rats using whole-cell patch-clamp technique. Hyperglycemia-induced increase in density of tetrodotoxin resistant (TTXr) Na(+) currents was increased in time- and concentration-dependent manner. The increase was maximal with 60 mM and 24 h. There was no change Na(+) current density in time-matched control neurons. The conductance curve of TTXr Na(+) current shifted leftward after 24 h exposure to 45 mM glucose. Carbamazepine (CBZ, 100 µM) depressed TTXr Na(+) current in neurons incubated with control (17.26), 45 and 60 mM of glucose. The depression observed with CBZ in the presence of high glucose, i.e., 45 mM (86.5±4.9%) was significantly greater than control (61.6±1.8%). Hyperglycemia also increased reactive oxygen species (ROS) activity and was attenuated by CBZ. These results suggest that short-term exposure of DRG neurons to high glucose concentrations enhance the Na(+) channel activity, and were attenuated by CBZ via ROS-dependent mechanisms.


Subject(s)
Ganglia, Spinal/physiopathology , Hyperglycemia/physiopathology , Neurons/physiology , Sodium/metabolism , Animals , Animals, Newborn , Antioxidants/pharmacology , Carbamazepine/pharmacology , Cells, Cultured , Ganglia, Spinal/drug effects , Glucose/metabolism , Hyperglycemia/drug therapy , Microscopy, Fluorescence , Neurons/drug effects , Patch-Clamp Techniques , Rats, Sprague-Dawley , Reactive Oxygen Species/metabolism , Sodium Channel Blockers/pharmacology , Sodium Channels/metabolism , Tetrodotoxin/pharmacology
18.
Oncogene ; 31(35): 3989-98, 2012 Aug 30.
Article in English | MEDLINE | ID: mdl-22158041

ABSTRACT

Mitotic catastrophe occurs when cells enter mitosis with damaged DNA or excess centrosomes. Cells overexpressing the centrosome protein CP110 or depleted of cyclin F, which targets CP110 for destruction, have more than two centrosomes and undergo mitotic catastrophe. Our studies show centrosome reduplication and mitotic catastrophe in osteosarcoma cells inducibly expressing a p27Kip1 mutant (termed p27K) that binds cyclins but not cyclin-dependent kinases (CDKs). p27K inhibited cell proliferation but not CDK activity or cell cycle progression. It did not induce apoptosis; however, cells expressing p27K had more than two centrosomes and, indicative of mitotic catastrophe, irregularly shaped nuclei or multiple micronuclei. p27K interacted with cyclin F in vivo (as did endogenous p27Kip1) and displaced cyclin F from CP110. Depletion of CP110 rescued p27K-expressing cells from centrosome reduplication and mitotic catastrophe. Collectively, our data show that p27Kip1 can perturb mitosis and suggest that it does so by sequestering cyclin F, which prevents its interaction with and the subsequent degradation of CP110, ultimately resulting in centrosome reduplication, mitotic catastrophe and abrogation of cell proliferation.


Subject(s)
Cell Cycle Proteins/metabolism , Centrosome/physiology , Cyclin-Dependent Kinase Inhibitor p27/genetics , Cyclin-Dependent Kinase Inhibitor p27/metabolism , Cyclin-Dependent Kinases/antagonists & inhibitors , Cyclins/metabolism , Microtubule-Associated Proteins/metabolism , Mitosis , Phosphoproteins/metabolism , Apoptosis/genetics , Cell Cycle/genetics , Cell Cycle Proteins/genetics , Cell Line, Tumor , Cell Nucleus/genetics , Cell Proliferation , Cyclins/deficiency , DNA Damage , Humans , Osteosarcoma/genetics , Osteosarcoma/pathology
19.
Neuroscience ; 199: 74-85, 2011 Dec 29.
Article in English | MEDLINE | ID: mdl-22037285

ABSTRACT

L-PGlu-(2-propyl)-L-His-L-ProNH2 (NP-647) is a CNS active thyrotropin-releasing hormone (TRH) analog with potential application in various CNS disorders including seizures. In the present study, mechanism of action for protective effect of NP-647 was explored by studying role of NP-647 on epileptiform activity and sodium channels by using patch-clamp methods. Epileptiform activity was induced in subicular pyramidal neurons of hippocampal slice of rat by perfusing 4-aminopyridine (4-AP) containing Mg⁺²-free normal artificial cerebrospinal fluid (nACSF). Increase in mean firing frequency was observed after perfusion of 4-AP and zero Mg⁺² (2.10±0.47 Hz) as compared with nACSF (0.12±0.08 Hz). A significant decrease in mean firing frequency (0.61±0.22 Hz), mean frequency of epileptiform events (0.03±0.02 Hz vs. 0.22±0.05 Hz of 4-AP+0 Mg), and average number of action potentials in paroxysmal depolarization shift-burst (2.54±1.21 Hz vs. 8.16±0.88 Hz of 4-AP+0 Mg) was observed. A significant reduction in peak dV/dt (246±19 mV ms⁻¹ vs. 297±18 mV ms⁻¹ of 4-AP+0 Mg) and increase (1.332±0.018 ms vs. 1.292±0.019 ms of 4-AP+0 Mg) in time required to reach maximum depolarization were observed indicating role of sodium channels. Concentration-dependent depression of sodium current was observed after exposure to dorsal root ganglion neurons to NP-647. NP-647 at different concentrations (1, 3, and 10 µM) depressed sodium current (15±0.5%, 50±2.6%, and 75±0.7%, respectively). However, NP-647 did not show change in the peak sodium current in CNa18 cells. Results of present study demonstrated potential of NP-647 in the inhibition of epileptiform activity by inhibiting sodium channels indirectly.


Subject(s)
Anticonvulsants/pharmacology , Neurons/drug effects , Thyrotropin-Releasing Hormone/analogs & derivatives , 4-Aminopyridine/toxicity , Action Potentials/drug effects , Animals , Convulsants/toxicity , Epilepsy/metabolism , Epilepsy/physiopathology , Ganglia, Spinal/drug effects , Ganglia, Spinal/metabolism , Hippocampus/drug effects , Hippocampus/metabolism , Neurons/metabolism , Organ Culture Techniques , Patch-Clamp Techniques , Rats , Rats, Wistar , Seizures/metabolism , Seizures/physiopathology , Sodium Channels/drug effects , Sodium Channels/metabolism , Thyrotropin-Releasing Hormone/pharmacology
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