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Biomedical subjects

A M Rao

Publications and source records attributed to A M Rao.

At least 19 recordsLinked to original sources

Electrochemical organization of monolayer protected gold nanoclusters on single-walled carbon nanotubes: significantly enhanced double layer capacitance.

This paper reports a novel electrochemical route for anchoring monolayer protected gold nanoclusters (size 8 +/- 0.2 nm) on single-walled carbon nanotube bundles, resulting in the formation of hybrid materials. Monolayer protected gold nanoclusters prepared by modified Brust synthesis route were organized on SWNT bundles by cycling the potential in dichloromethane between -1 to +1 V at a scan rate of 50 mV/s. Monolayer protected nanoclusters in electrolyte solutions possess ionic space charge around them (double layer charging), making them suitable for organization on nanotube bundles, by tuning the electrostatic interactions. More significantly, analysis of the double layer capacitance of these hybrid materials shows almost ten times increase in capacitance compared to that of bare SWNT bundles. We believe that these hybrid materials are potentially useful in nanoelectronics.

Crystallization↗

A GH receptor antisense oligonucleotide inhibits hepatic GH receptor expression, IGF-I production and body weight gain in normal mice.

Diabetic retinopathy and acromegaly are diseases associated with excess action of GH and its effector IGF-I, and there is a need for improved therapies. We have designed an optimised 2'-O-(2-methoxyethyl)-modified phosphorothioate oligodeoxynucleotide, ATL 227446, and demonstrated its ability to suppress GH receptor mRNA in vitro. Subcutaneous injections of ATL 227446 reduced GH receptor mRNA levels, GH binding activity and serum IGF-I levels in mice after seven days of dosing. The reduction in serum IGF-I could be sustained for over ten weeks of dosing at therapeutically relevant levels, during which there was also a significant decrease in body weight gain in antisense-treated mice relative to saline and mismatch control-treated mice. The findings indicate that administration of an antisense oligonucleotide to the GH receptor may be applicable to human diseases in which suppression of GH action provides therapeutic benefit.

Animals↗

Novel electrical switching behaviour and logic in carbon nanotube Y-junctions.

Carbon-nanotube-based electronics offers significant potential as a nanoscale alternative to silicon-based devices for molecular electronics technologies. Here, we show evidence for a dramatic electrical switching behaviour in a Y-junction carbon-nanotube morphology. We observe an abrupt modulation of the current from an on- to an off-state, presumably mediated by defects and the topology of the junction. The mutual interaction of the electron currents in the three branches of the Y-junction is shown to be the basis for a potentially new logic device. This is the first time that such switching and logic functionalities have been experimentally demonstrated in Y-junction nanotubes without the need for an external gate. A class of nanoelectronic architecture and functionality, which extends well beyond conventional field-effect transistor technologies, is now possible.

Crystallization↗

Determination of the bending modulus of an individual multiwall carbon nanotube using an electric harmonic detection of resonance technique.

We report a new method of measuring the amplitude and phase of oscillations of individual multiwall carbon nanotubes (MWNTs). As in many other experiments, we excite the oscillations electrostatically, but we show that we can detect the amplitude and phase of the resulting oscillation electrically. As an example, we present measurements of the fundamental and first two overtones of the diving board resonance of a MWNT at 0.339, 2.42, and 5.31 MHz in ambient conditions. The corresponding quality factors were 67, 36, and 25.

Algorithms↗

ZnO nanowires by pulsed laser vaporization: synthesis and properties.

We report a new pulsed-laser vaporization (PLV) technique to synthesize nanowires of single-crystal ZnO having a wurtzite structure by using colloidal gold nanoparticles as seeding catalysts. The average diameter of the nanowires is approximately 13 nm, with a very narrow range of 7 to 25 nm. The nanowires are straight for the most part, with the axes parallel to the [0001] growth direction. Raman and photoluminescence spectra from the nanowires and bulk ZnO are similar except for a approximately 510 nm band in the nanowires due to oxygen vacancies. The bulk-like vibrational and electronic properties of the nanowires is due to the diameter being larger than the threshold below which quantum confinement-induced effects are expected.

Crystallization↗

Raman studies of semiconducting oxide nanobelts.

Crystalline nanobelts of ZnO and SnO2 were prepared from a thermal evaporation of oxide powders inside an alumina tube in the absence of catalysts. Typical dimensions of the nanobelt samples ranged from approximately 10 to 100 microns in length, 30 to 300 nm in width, and 6 to 30 nm in thickness. Room temperature Raman spectra were obtained on pressed mats of nanobelt samples and compared with the corresponding spectra of the starting oxide powders and bulk materials. Collectively, our Raman data indicated that the as-prepared nanobelt samples used in this study were oxygen deficient. Upon annealing at 900 degrees C in flowing oxygen for 1 h, the nanobelt samples exhibited Raman features that corresponded to those expected in respective bulk semiconducting oxides. The dimensions of the nanobelts were a bit too large to expect significant quantum size effects on the phonon structure similar to those observed in carbon nanotubes and short-period semiconductor superlattices.

Aluminum↗

Monitoring of indoor volatile organic compounds and polycyclic aromatic hydrocarbons arising from kerosene cooking fuel.

Air samples, representing indoor environments of a kitchen in which a kerosene stove was used were collected and analysed for volatile organic compounds (VOCs) viz., n-hexane, benzene, heptane, toluene, p- and o-xylene and n-decane using a cryogenic preconcentration system and a gas chromatograph with a flame-ionisation detector. Simultaneous outdoor samples were also collected to determine indoor to outdoor (I/O) ratios for each compound. Reversed phase high performance liquid chromatography (HPLC) with ultra violet absorption detection was optimised for separation and quantification of polycyclic aromatic hydrocarbons (PAHs) in air particulate matter. Concentration of total suspended particulate matter (TSPM), benzene soluble organics and the PAHs in air samples collected in indoor environment of some tenements at Trombay, Mumbai where kerosene is used as cooking fuel are discussed in relation to the concentration of the same in outdoor environment in vicinity of the tenement. VOCs and PAHs results from samples collected in kitchens in Trombay are discussed in relation to indoor air pollution.

Air Pollution, Indoor↗

Up-regulation of the peripheral-type benzodiazepine receptor expression and [(3)H]PK11195 binding in gerbil hippocampus after transient forebrain ischemia.

In mammalian CNS, the peripheral-type benzodiazepine receptor (PTBR) is localized on the outer mitochondrial membrane within the astrocytes and microglia. The main function of PTBR is to transport cholesterol across the mitochondrial membrane to the site of neurosteroid biosynthesis. The present study evaluated the changes in the PTBR density, gene expression and immunoreactivity in gerbil hippocampus as a function of reperfusion time after transient forebrain ischemia. Between 3 to 7 days of reperfusion, there was a significant increase in the maximal binding site density (B(max)) of the PTBR antagonist [(3)H]PK11195 (by 94-156%; P < 0.01) and PTBR mRNA levels (by 1.8- to 2.9-fold; P < 0.01). At 7 days of reperfusion, in the hippocampal CA1 (the brain region manifesting selective neuronal death), PTBR immunoreactivity increased significantly. Increased PTBR expression after transient forebrain ischemia may lead to increased neurosteroid biosynthesis, and thus may play a role in the ischemic pathophysiology.

Animals↗

Effect of van der Waals interactions on the Raman modes in single walled carbon nanotubes.

We have measured the Raman spectrum of individual single walled carbon nanotubes in solution and compare it to that obtained from the same starting material where the tubes are present in ordered bundles or ropes. Interestingly, the radial mode frequencies for the tubes in solution are found to be approximately 10 cm (-1) higher than those observed for tubes in a rope, in apparent contradiction to lattice dynamics predictions. We suggest that there is no such contradiction, and propose that the upshift is due rather to a decreased energy spacing of the Van Hove singularities in isolated tubes over the spacings in a rope, thereby allowing the same laser excitation to excite different diameter tubes in these two samples.

Journal Article↗

Does CDP-choline modulate phospholipase activities after transient forebrain ischemia?

Ten min forebrain ischemia/1-day reperfusion resulted in significant decreases in total phosphatidylcholine (PtdCho), phosphatidylinositol (PtdIns), and cardiolipin in gerbil hippocampus. CDP-choline restored cardiolipin levels, arachidonic acid content of PtdCho, partially but significantly restored total PtdCho, and had no effect on PtdIns. These data suggest that CDP-choline prevented the activation of phospholipase A(2) (rather than inhibiting phospholipase A(2) activity) but did not affect activities of PtdCho-phospholipases C and/or D, or phosphoinositide-phospholipase C. CDP-choline also provided significant protection for hippocampal CA(1) neurons.

Animals↗

Monitoring of organochlorine pesticide residues in the Indian marine environment.

Organochlorine pesticide residues in sediment and fish samples collected from the east and west coasts of India are presented. HCH isomers and DDT and its metabolites are the predominantly identified compounds in most of the samples. Despite the higher quantity of consumption, HCH and DDT levels in fish in India were lower than those in temperate countries suggesting a lower accumulation in tropical fish, which could be due to rapid volatilization and degradation of these insecticides in the tropical environment. The predominance of alpha- and beta-HCH reflect the use of technical grade HCH in India. The high temperature in the tropics also enhances the elimination rate of chemicals in fish, as the biological half-lives of semivolatile compounds such as DDT are short at high temperature.

Animals↗

Neuroprotection by group I metabotropic glutamate receptor antagonists in forebrain ischemia of gerbil.

Stimulation of group I metabotropic glutamate receptors (mGluR 1 and 5) activates G-protein coupled-phospholipase C (PLC) to release 1,2-diacylglycerol (DAG) and arachidonic acid (ArAc). To elucidate the role of group I mGluR, we tested the effects of (S)-alpha-methyl-4-carboxy-phenylglycine (MCPG, mGluR 1 and 5 antagonist), 1-aminoindan-1,5-dicarboxylic acid (AIDA, mGluR 1a specific antagonist) and 2-methyl-6-(phenylethynyl) pyridine (MPEP, mGluR 5 antagonist) on ArAc release and neuronal survival after transient forebrain ischemia in gerbils. Ischemia resulted in (a) significant release of ArAc at 1-day reperfusion and (b) significant neuronal death in the hippocampal CA1 subfield after 6-day reperfusion. MCPG and MPEP decreased ArAc release and also significantly increased neuronal survival. AIDA was less effective in decreasing ArAc release and had no effect on neuronal death. These results suggest that activation of mGluR 5 may be an important pathway in ArAc release and neuronal death after transient ischemia.

Animals↗

Glial glutamate transporter GLT-1 down-regulation precedes delayed neuronal death in gerbil hippocampus following transient global cerebral ischemia.

Glial (GLT-1 and GLAST) and neuronal (EAAC1) high-affinity transporters mediate the sodium dependent glutamate reuptake in mammalian brain. Their dysfunction leads to neuronal damage by allowing glutamate to remain in the synaptic cleft for a longer duration. The purpose of the present study is to understand their contribution to the ischemic delayed neuronal death seen in gerbil hippocampus following transient global cerebral ischemia. The protein levels of these three transporters were studied by immunoblotting as a function of reperfusion time (6 h to 7 days) following a 10 min occlusion of bilateral common carotid arteries in gerbils. In the vulnerable hippocampus, there was a significant decrease in the protein levels of GLT-1 (by 36-46%, P < 0.05; between 1 and 3 days of reperfusion) and EAAC1 (by 42-68%, P < 0.05; between 1 and 7 days of reperfusion). Histopathological evaluation showed no neuronal loss up to 2 days of reperfusion but an extensive neuronal loss (by approximately 84%, P < 0.01) at 7 days of reperfusion in the hippocampal CA1 region. The time frame of GLT-1 dysfunction (1-3 days of reperfusion) precedes the initiation of delayed neuronal death (2-3 days of reperfusion). This suggests GLT-1 dysfunction as a contributing factor for the hippocampal neuronal death following transient global cerebral ischemia. Furthermore, decreased EAAC1 levels may contribute to GABAergic dysfunction and excitatory/inhibitory imbalance following transient global ischemia.

ATP-Binding Cassette Transporters↗

Lipid alterations in transient forebrain ischemia: possible new mechanisms of CDP-choline neuroprotection.

We have previously demonstrated that cytidine 5'-diphosphocholine (CDP-choline or citicoline) attenuated arachidonic acid (ArAc) release and provided significant protection for the vulnerable hippocampal CA(1) neurons of the cornu ammonis after transient forebrain ischemia of gerbil. ArAc is released by the activation of phospholipases and the alteration of phosphatidylcholine (PtdCho) synthesis. Released ArAc is metabolized by cyclooxygenases/lipoxygenases to form eicosanoids and reactive oxygen species (ROS). ROS contribute to neurotoxicity through generation of lipid peroxides and the cytotoxic byproducts 4-hydroxynonenal and acrolein. ArAc can also stimulate sphingomyelinase to produce ceramide, a potent pro-apoptotic agent. In the present study, we examined the changes and effect of CDP-choline on ceramide and phospholipids including PtdCho, phosphatidylethanolamine (PtdEtn), phosphatidylinositol (PtdIns), phosphatidylserine (PtdSer), sphingomyelin, and cardiolipin (an exclusive inner mitochondrial membrane lipid essential for electron transport) following ischemia/1-day reperfusion. Our studies indicated significant decreases in total PtdCho, PtdIns, PtdSer, sphingomyelin, and cardiolipin and loss of ArAc from PtdEtn in gerbil hippocampus after 10-min forebrain ischemia/1-day reperfusion. CDP-choline (500 mg/kg i.p. immediately after ischemia and at 3-h reperfusion) significantly restored the PtdCho, sphingomyelin, and cardiolipin levels as well as the ArAc content of PtdCho and PtdEtn but did not affect PtdIns and PtdSer. These data suggest multiple beneficial effects of CDP-choline: (1) stabilizing the cell membrane by restoring PtdCho and sphingomyelin (prominent components of outer cell membrane), (2) attenuating the release of ArAc and limiting its oxidative metabolism, and (3) restoring cardiolipin levels.

Animals↗

Elevated N1-acetylspermidine levels in gerbil and rat brains after CNS injury.

The polyamine system is very sensitive to different pathological states of the brain and is perturbed after CNS injury. The main modifications are significant increases in ornithine decarboxylase activity and an increase in tissue putrescine levels. Previously we have shown that the specific polyamine oxidase (PAO) inhibitor N1,N4-bis(2,3-butadienyl)-1,4-butanediamine (MDL 72527) reduced the tissue putrescine levels, edema, and infarct volume after transient focal cerebral ischemia in spontaneously hypertensive rats and traumatic brain injury of Sprague-Dawley rats. In the present study, N1-acetyl-spermidine accumulation was greater in injured brain regions compared with sham or contralateral regions following inhibition of PAO by MDL 72527. This indicates spermidine/spermine-N1-acetyltransferase (SSAT) activation after CNS injury. The observed increase in N1-acetylspermidine levels at 1 day after CNS trauma paralleled the decrease in putrescine levels after treatment with MDL 72527. This suggests that the increased putrescine formation at 1 day after CNS injury is mediated by the SSAT/PAO pathway, consistent with increased SSAT mRNA after transient ischemia.

Animals↗

Molecular functionalization of carbon nanotubes and use as substrates for neuronal growth.

Carbon nanotubes are strong, flexible, conduct electrical current, and can be functionalized with different molecules, properties that may be useful in basic and applied neuroscience research. We report the first application of carbon nanotube technology to neuroscience research. Methods were developed for growing embryonic rat-brain neurons on multiwalled carbon nanotubes. On unmodified nanotubes, neurons extend only one or two neurites, which exhibit very few branches. In contrast, neurons grown on nanotubes coated with the bioactive molecule 4-hydroxynonenal elaborate multiple neurites, which exhibit extensive branching. These findings establish the feasability of using nanotubes as substrates for nerve cell growth and as probes of neuronal function at the nanometer scale.

Aldehydes↗

Neuroprotective effects of citicoline on brain edema and blood-brain barrier breakdown after traumatic brain injury.

OBJECT: Cytidine 5'-diphosphocholine (CDPC), or citicoline, is a naturally occurring endogenous compound that has been reported to provide neuroprotective effects after experimental cerebral ischemia. However, in no study has such protection been shown after traumatic brain injury (TBI). In this study the authors examined the effect of CDPC on secondary injury factors, brain edema and blood-brain barrier (BBB) breakdown, after TBI. METHODS: After anesthesia had been induced in Sprague-Dawley rats by using 1.5% halothane, an experimental TBI was created using a controlled cortical impact (CCI) device with a velocity of 3 m/second, resulting in a 2-mm deformation. Four sham-operated control animals used for brain edema and BBB breakdown studies underwent the same surgical procedure, but received no injury. Brain edema was evaluated using the wet-dry method 24 hours postinjury, and BBB breakdown was evaluated by measuring Evans blue dye (EBD) extravasation with fluorescein 6 hours after TBI. The animals received intraperitoneal injections of CDPC (50, 100, or 400 mg/kg two times after TBI [eight-10 animals in each group]) or saline (eight animals) after TBI. Traumatic brain injury induced an increase in the percentage of water content and in EBD extravasation in the injured cortex and the ipsilateral hippocampus. No significant benefit from CDPC treatment was observed at a dose of 50 mg/kg. Cytidine 5'-diphosphocholine at a dose of 100 mg/kg attenuated EBD extravasation in both regions, although it reduced brain edema only in the injured cortex. In both regions, 400 mg/ kg of CDPC significantly decreased brain edema and BBB breakdown. CONCLUSIONS: This is the first report in which dose-dependent neuroprotective effects of CDPC have been demonstrated in the injured cortex as well as in the hippocampus, a brain region known to be vulnerable to injury, after experimental TBI. The results of this study suggest that CDPC is an effective neuroprotective agent on secondary injuries that appear following TBI.

Animals↗

CDP-choline: neuroprotection in transient forebrain ischemia of gerbils.

CDP-choline is a rate-limiting intermediate in the biosynthesis of phosphatidylcholine (PtdCho), an important component of the neural cell membrane. The ability of CDP-choline to alter phospholipid metabolism is an important function in the treatment of ischemic injury. Exogenous treatment with CDP-choline stimulates PtdCho synthesis and prevents release of free fatty acids (FFA), especially arachidonic acid (AA), after ischemia/reperfusion. Phase III clinical trials of CDP-choline in the treatment of stroke are currently underway. Here we report the neuroprotection by CDP-choline in transient forebrain ischemia of gerbils. CDP-choline significantly attenuated the blood-brain barrier (BBB) dysfunction after ischemia with 6-hr reperfusion, and considerably reduced the increase of AA in FFA and leukotriene C(4) (LTC(4)) synthesis at 1 day. Edema was significantly elevated after 1 and 2 days, but attained maximum at 3-day reperfusion. CDP-choline substantially attenuated edema at 3 days. Ischemia resulted in 80 +/- 8% CA(1) hippocampal neuronal death after 6-day reperfusion, and CDP-choline provided 65 +/- 6% neuroprotection. CDP-choline may act by increasing PtdCho synthesis via two pathways: (1) conversion of 1, 2-diacylglycerol to PtdCho, and (2) biosynthesis of S-adenosyl-L-methionine, thus stabilizing the membrane and reducing AA release and metabolism to leukotriene C(4). This would result in decreased toxicity due to AA, leukotrienes, oxygen radicals, lipid peroxidation, and altered glutamate uptake, thus limiting BBB dysfunction, edema and providing neuroprotection.

Animals↗