Biomedical subjects

Abhijit Chatterjee

Publications and source records attributed to Abhijit Chatterjee.

26 records · Page 2Linked to original sources

PubMed2004

Spatially adaptive lattice coarse-grained Monte Carlo simulations for diffusion of interacting molecules.

While lattice kinetic Monte Carlo (KMC) methods provide insight into numerous complex physical systems governed by interatomic interactions, they are limited to relatively short length and time scales. Recently introduced coarse-grained Monte Carlo (CGMC) simulations can reach much larger length and time scales at considerably lower computational cost. In this paper we extend the CGMC methods to spatially adaptive meshes for the case of surface diffusion (canonical ensemble). We introduce a systematic methodology to derive the transition probabilities for the coarse-grained diffusion process that ensure the correct dynamics and noise, give the correct continuum mesoscopic equations, and satisfy detailed balance. Substantial savings in CPU time are demonstrated compared to microscopic KMC while retaining high accuracy.

Journal Article↗

PubMed2004

Effects of leptin and neuropeptide-Y on transcript levels of thyrotropin beta and common alpha subunits of rat pituitary cells in vitro.

Leptin and neuropeptide-Y (NPY) are indicated to play a role in hypothalamo-pituitary-thyroid (HPT) axis in relation to regulation of energy homeostasis mediated through acting at hypothalamic synthesis and release of thyrotropin (TSH)-releasing hormone (TRH). Whether leptin and NPY also act at pituitary level in HPT axis remains unknown. This study aimed at investigating whether or not leptin and NPY exert actions at pituitary in modulation of transcript levels of TSHbeta and the common pituitary glycoprotein hormone alpha (PGHalpha) subunits. The dispersed pituitary cells from 6 wk old male Wistar rats were incubated with or without TRH, leptin or NPY of 10(-8) M and 10(-10) M for 6 h at 37 degrees C in medium-199 under aeration of 95% O2 and 5% CO2. The mRNA levels of TSHbeta and PGHalpha subunits of the incubated cells were measured by reverse transcription-polymerase chain reaction. The results revealed that leptin stimulated, while NPY inhibited, TSHbeta mRNA levels in a dose-related manner. Both leptin and NPY increased alpha subunit mRNA levels. It is demonstrated for the first time that both leptin and NPY exert a direct action at rat pituitary affecting steady-state levels of mRNA of TSHbeta and PGHalpha subunits. The present study supports that both leptin and NPY act at the pituitary as well besides the hypothalamus in HPT axis in relation to regulation of energy homeostasis.

Analysis of Variance↗

PubMed2004

Effect of exchangeable cation on the swelling property of 2:1 dioctahedral smectite--a periodic first principle study.

We used both localized and periodic calculations on a series of monovalent (Li+, Na+, K+, Rb+, Cs+) and divalent (Mg2+, Ca2+, Sr2+, Ba2+) cations to monitor their effect on the swelling of clays. The activity order obtained for the exchangeable cations among all the monovalent and divalent series studied: Ca2+ > Sr2+ > Mg2+ > Rb+ > Ba2+ > Na+ > Li+ > Cs+ > K+. We have shown that, in case of dioctahedral smectite, the hydroxyl groups play a major role in their interaction with water and other polar molecules in the presence of an interlayer cation. We studied both type of clays, with a different surface structure and with/without water using a periodic calculation. Interlayer cations and charged 2:1 clay surfaces interact strongly with polar solvents; when it is in an aqueous medium, clay expands and the phenomenon is known as crystalline swelling. The extent of swelling is controlled by a balance between relatively strong swelling forces and electrostatic forces of attraction between the negatively charged phyllosilicate layer and the positively charged interlayer cation. We have calculated the solvation energy at the first hydration shell of an exchangeable cation, but the results do not correspond directly to the experimental d-spacing values. A novel quantitative scale is proposed with the numbers generated by the relative nucleophilicity of the active cation sites in their hydrated state through Fukui functions within the helm of the hard soft acid base principle. The solvation effect thus measured show a perfect match with experiment, which proposes that the reactivity index calculation with a first hydration shell could rationalize the swelling mechanism for exchangeable cations. The conformers after electron donation or acceptance propose the swelling mechanism for monovalent and divalent cations.

Journal Article↗

PubMed2004

Effect of a selective cyclooxygenase-2 inhibitor, nimesulide, on the growth of lung tumors and their expression of cyclooxygenase-2 and peroxisome proliferator- activated receptor-gamma.

PURPOSE: The objectives of this study were to evaluate the effect of a cyclooxygenase (COX)-2 inhibitor, nimesulide, on the growth inhibition of s.c. human lung A549 adenocarcinoma tumors and to assess the effect of nimesulide on the expression of COX-2 and peroxisome proliferator-activated receptor (PPAR)-gamma in lung tumors harvested from mice. EXPERIMENTAL DESIGN: Female nu/nu mice were xenografted with s.c. A549 lung tumors, and 1 day after tumor implantation, the mice were fed with a diet containing nimesulide at 250-1500 ppm doses. Tumor dimensions were monitored twice weekly, and tumor samples isolated from mice were used to determine prostaglandin E(2) (PGE(2)) levels by enzyme immunoassay, expression of COX-2 and PPAR-gamma by Western blotting and immunohistochemistry. Furthermore, the induction of apoptosis in tumor specimens was determined by terminal deoxynucleotidyl transferase-mediated nick end labeling staining. RESULTS: Nimesulide treatment showed a dose-dependent growth-inhibitory effect of A549 tumors with a maximum of 77.7% inhibition at 1500 ppm of nimesulide. Western blotting experiments showed similar expression of COX-2 in both control and nimesulide (250-1500 ppm)-treated mice tumor tissues. PPAR-gamma was found to be overexpressed as a result of 1500 ppm nimesulide treatment and was not detected in tumors from control or 250-1000 ppm nimesulide-treated mice. Nimesulide (1500 ppm) significantly reduced intratumor PGE(2) levels (P < 0.001) and induced apoptosis in 25% of tumor cells as compared with control tumors. CONCLUSIONS: Nimesulide (1500 ppm) induced growth inhibition of A549 lung tumors is associated with the reduction of intratumor PGE(2) levels but without affecting the expression of COX-2. Nimesulide-induced enhancement of the expression of PPAR-gamma may also contribute to its antitumor effect, which needs to be further investigated.

Animals↗

PubMed2004

Effects of monensin liposomes on the cytotoxicity, apoptosis and expression of multidrug resistance genes in doxorubicin-resistant human breast tumour (MCF-7/dox) cell-line.

We have evaluated the effects of monensin liposomes on drug resistance reversal, induction of apoptosis and expression of multidrug resistance (MDR) genes in a doxorubicin-resistant human breast tumour (MCF-7/dox) cell line. Monensin liposomes were prepared by the pH-gradient method. MCF-7/dox cells were treated with various anticancer drugs (doxorubicin, paclitaxel and etoposide) alone and in combination with monensin liposomes. The cytotoxicity was assessed using the crystal violet dye uptake method. The induction of apoptosis in MCF-7/dox cells was assessed by established techniques such as TUNEL (terminal deoxynucleotidyl transferase-mediated nick end labelling) staining and caspase-3 assay. The effect of monensin liposomes on doxorubicin accumulation in MCF-7/dox cells was monitored by fluorescent microscopy. Finally, the expression of MDR genes (MDR1 and MRP1) in MCF-7/dox cells following the exposure to doxorubicin alone and in combination with monensin liposomes was evaluated by semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). Our results indicated that monensin liposomes overcame drug resistance in MCF-7/dox cells to doxorubicin, etoposide and paclitaxel by 16.5-, 5.6- and 2.8-times, respectively. The combination of doxorubicin (2.5 microg mL(-1)) with monensin liposomes (20 x 10(-8)M) induced apoptosis in approximately 40% cells, whereas doxorubicin (2.5 microg mL(-1)) or monensin liposomes (20 x 10(-8)M) alone produced minimal apoptosis (<10%) in MCF-7/dox cells. Fluorescent microscopy revealed that monensin liposomes increased the accumulation of doxorubicin in MCF-7/dox cells. RT-PCR studies demonstrated that the expression of MDR1 and MRP1 was increased by 33 and 57%, respectively, in MCF-7/dox cells following treatment with doxorubicin (2.5 microg mL(-1)) for 72 h as compared with control MCF-7/dox cells. Furthermore, the levels of MDR1 and MRP1 in MCF-7/dox cells exposed to both doxorubicin and monensin liposomes showed a modest decrease as compared with MCF-7/dox cells treated with doxorubicin alone. In conclusion, the delivery of monensin via liposomes provided an opportunity to overcome drug resistance.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2003

A density functional study to choose the best fluorophore for photon-induced electron-transfer (PET) sensors.

Anthracenes bearing aliphatic or aromatic amino substituents, which behave as molecular sensors, have shown their potential to act as photon-induced electron-transfer (PET) systems. In this PET, the fluorophore moieties are responsible for electron release during protonation and deprotonation. The principle of hard and soft acids and bases (HSAB) deals with both intra- and intermolecular electron migration. It is possible to calculate the localized properties in terms of Fukui functions in the realm of density functional theory (DFT) and thus calculate and establish a numerical matchmaking procedure that will generate an a priori rule for choosing the fluorophore in terms of its activity. We calculated the localized properties for neutral, anionic, and cationic systems to trace the course of the efficiency. A qualitative scale is proposed in terms of the feasibility of intramolecular hydrogen bonding. To investigate the effect of the environment of the nitrogen atom on protonation going from mono- to diprotonated systems, we calculated the partial density of states and compared the activity sequence with reactivity indices. The results show that location of the nitrogen atom in an aromatic ring does not influence the PET, but for aliphatic chains it plays a role. Furthermore, the protonation/deprotonation scenario has been explained. The results show that the reactivity indices can be used as a suitable property for scaling the activity of fluorophore molecules for the PET process.

Journal Article↗

PubMed2003

2,3,7,8-Tetrachloro dibenzo-p-dioxin can be successfully decomposed over 2:1 dioctahedral smectite-a reactivity index study.

2:1 Dioctahedral smectite family has shown its capability to decompose 2,3,7,8-tetrachloro dibenzo-p-dioxin (TeCDD) using the active hydroxyl hydrogen attached with the central octahedral aluminum, as monitored using density functional theory (DFT). From the values of the local softness and the charge on the hydrogen atom of the bridging/structural (occurring on the surface) hydroxyl attached to octahedral/tetrahedral metal site present in smectite used as a first approximation to the local hardness, it is concluded that the local acidities of the inorganic material systems are dependent on several characteristics which are of importance within the framework of hard-soft acid-base (HSAB) principle. The first step in this process of decomposition is the abstraction of chlorine bound to TeCDD using surface hydrogen of smectites. This results in non-chlorinated dibenzo-p-dioxin (NCDD), which is less toxic than TeCDD. The second step is the formation of a dative bond between oxygen of NCDD and hydroxyl proton of smectite, with the breaking of Cz.sbnd;O bond of NCDD. The reaction mechanism is postulated within the helm of DFT using Fukui functions for all possible chlorinated and non-chlorinated dioxin varieties along with clay clusters. The material is identified to act for the decomposition of dioxin.

Computer-Aided Design↗

PubMed2003

Evaluation of an aerosolized selective COX-2 inhibitor as a potentiator of doxorubicin in a non-small-cell lung cancer cell line.

PURPOSE: To evaluate the in vitro effects of an aerosolized cyclooxygenase-2 (COX-2) inhibitor, nimesulide, on the cytotoxicity and apoptotic response of doxorubicin against the human lung adenocarcinoma cell line A549. METHODS: Nimesulide was formulated into a metered dose inhaler (MDI) formulation and characterized for aerodynamic particle size and medication delivery. The in vitro cytotoxicity of nimesulide-MDI in the presence or absence of doxorubicin was assessed by using the six-stage viable impactor by an already standardized method. Induction of apoptosis in A549 cells by nimesulide (nonaerosolized or aerosolized) in combination with doxorubicin was evaluated by established techniques such as caspase-3 estimation and terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) staining. Finally, to understand the mechanism of action, the influence of different treatments on the expression of COX-2 and peroxisome proliferator-activated receptor-gamma (PPAR-gamma) in A549 cells was studied by immunoblotting. RESULTS: The nimesulide-MDI formulation had a mass median aerodynamic diameter (MMAD) of 1.1 microm, (GSD = 2.8) and a medication delivery of 51 microg/shot. Nimesulide-MDI (40 shots) in combination with doxorubicin (0.01 microg/ml) had a cell kill of more than 60% as determined by in vitro cytotoxicity assay. The specific caspase-3 activity in A549 cells treated with nimesulide (40 microg/ml) and doxorubicin (0.25 microg/ml) in combination was 3 and 5 times higher than doxorubicin and nimesulide, respectively. Further, TUNEL staining showed apoptosis in over 30% of A549 cells treated with aerosolized nimesulide and doxorubicin combination vs. negligible as seen in cells treated individually. The expression of COX-2 was not altered in control or treatments, whereas PPAR-gamma was expressed only in the combination treatment. CONCLUSION: Our results indicate that aerosolized nimesulide significantly enhances doxorubicin activity against A549 cells, and the enhanced cytotoxicity was probably mediated via a COX-2-independent mechanism.

Aerosols↗