Thiophene Appended Dual Fluorescent Sensor for Detection of Hg2+ and Cysteamine.

An efficient and highly selective pyrene-thiophene conjugate has been reported as a dual sensor for Hg2+ and cysteamine (an important drug for genetic disorder). The sensor displays a turn-on fluorescence response towards Hg2+ in a 2:1 stoichiometric ratio via excimer formation with a detection limit as low as of 30.6 nM. The excimer emission upon binding with Hg2+ has been rationalized by experimental as well as theoritical studies. Moreover, the [probe-Hg2+] adduct functions as an efficient sensor for cysteamine. This sensing process happens via the extraction of Hg2+ from the adduct. In this paper, change in emission properties of the receptor with varying pH and water content has also been explained. The sensing abilities of the sensor were examined in real water sample analysis. Therefore, the sensor can be used as an efficient and reusable fluorescent sensor for recognition of Hg2+ in water.

Enantioselective Tissue Distribution of Ketorolac and its Enantiomers in Rats.

The difference in tissue distribution of Ketorolac and its enantiomers were investigated in wistar rats. Separate high performance liquid chromatographic method was developed and validated for determination of Ketorolac and its enantiomers. Oyster BDS (150 × 4.6 mm id., 5 µm particle size) column was used for determination of concentration of Ketorolac. Ketorolac enantiomers were determined using Chiral-AGP column (100 × 4.0 mm I.D., particle size 5 µ, Chrom tech Ltd, Sweden). Detection was done at wavelength of 322 nm using an ultraviolet detector in the analytical system. Ketorolac enantiomers exhibit difference in their disposition in Wistar rats. In kidney, there was a significant difference in pharmacokinetic parameters. The Cmax was nearly 4 times and AUC 0-∞ was found to be more than double for S (-) Ketorolac than that of R (+) Ketorolac. MRT, Ke and t1/2 differ significantly in kidney. In liver, Cmax was found to be approximately 69% higher for S (-) Ketorolac compared to R (+) Ketorolac. AUC 0-∞ did not differ significantly for the enantiomers in liver. In liver, S (-) Ketorolac eliminated very fast in comparison to R (+) Ketorolac having t1/2 (one third) in comparison to R (+) Ketorolac. In lungs, there was no difference observed for Cmax and other parameters but AUC 0-∞ was found to be marginally higher for S (-) ketorolac.

A pyrene-based simple but highly selective fluorescence sensor for Cu(2+) ions via a static excimer mechanism.

A pyrene-based simple fluorosensor has been synthesized by a one step process. It exhibited high selectivity towards Cu(2+) ions via fluorescence enhancement of monomer and excimer emission. The origin of excimer formation was examined and established to be of static in nature from the study of absorption and excitation spectra. The observed monomer and excimer emission in the presence and absence of Cu(2+) ion with varying pH was studied and provided probable justification. The effect of varying portions of water content in solvent on the sensor molecule was also examined. The sensor found its proper application in finding accurate and trace amount of Cu(2+) ions present in drinking water samples from various sources. The detection limit of the current sensor was found to be 4 × 10(-8) M.

Rapid and Sensitive Reverse-phase High-performance Liquid Chromatography Method for Estimation of Ketorolac in Pharmaceuticals Using Weighted Regression.

A reliable, rapid and sensitive isocratic reverse phase high-performance liquid chromatography method has been developed and validated for assay of ketorolac tromethamine in tablets and ophthalmic dosage forms using diclofenac sodium as an internal standard. An isocratic separation of ketorolac tromethamine was achieved on Oyster BDS (150×4.6 mm i.d., 5 µm particle size) column using mobile phase of methanol:acetonitrile:sodium dihydrogen phosphate (20 mM; pH 5.5) (50:10:40, %v/v) at a flow rate of 1.0 ml/min. The eluents were monitored at 322 nm for ketorolac and at 282 nm for diclofenac sodium with a photodiode array detector. The retention times of ketorolac and diclofenac sodium were found to be 1.9 min and 4.6 min, respectively. Response was a linear function of drug concentration in the range of 0.01-15 µg/ml (R (2)=0.994; linear regression model using weighing factor 1/x (2)) with a limit of detection and quantification of 0.002 µg/ml and 0.007 µg/ml, respectively. The % recovery and % relative standard deviation values indicated the method was accurate and precise.

Splitting hares and tortoises: a classification of neuronal immediate early gene transcription based on poised RNA polymerase II.

Immediate early transcription is an integral part of the neuronal response to environmental stimulation and serves many brain processes including development, learning, triggers of programmed cell death, and reaction to injury and drugs. Following a stimulus, neurons express a select few genes within a short period of time without undergoing de novo protein translation. Referred to as the 'gateway to genetic response', these immediate early genes (IEGs) are either expressed within a few minutes of stimulation or later within the hour. In neuronal IEGs that are expressed rapidly, productive elongation in response to neuronal activity is jump-started by constitutive transcription initiation together with RNA polymerase II stalling in the vicinity of the promoter. IEGs expressed later in the hour do not depend on this mechanism. On the basis of this Polymerase II poising, we propose that the immediate early genes can be grouped in two distinct classes: the rapid and the delayed IEGs. The possible biological relevance of these classes in neurons is discussed.

Enantioselective disposition after single dose I.V administration of ketorolac in male Wistar rats.

Ketorolac, a commonly used anti-inflammatory and analgesic agent, was studied in male wistar rats. The plasma samples were analysed using chiral AGP column with UV detection. The experimental data was analysed for probable fit in the compartmental and non-compartmental models using WinNolin software. The data of (+)-R-Ketorolac and (-)-S-Ketorolac was found to fit into the compartmental as well as non compartmental model. There was a difference between the plasma concentrations of (+)-R-Ketorolac and (-)-S-Ketorolac; the plasma concentrations of (+)-R-Ketorolac were higher than those of (-)-S-Ketorolac throughout the time course of the study. The area under the curve (AUC) of time vs. concentration profile of (+)-R-Ketorolac was found to be higher than (-)-S-Ketorolac. Volume of distribution and clearance was found to be higher for (-)-S-Ketorolac.

Rapid sensitive validated UPLC-MS method for determination of venlafaxine and its metabolite in rat plasma: Application to pharmacokinetic study.

A new ultra-performance liquid chromatography-electrospray ionization mass spectrometry (UPLC-MS/ESI) method for simultaneous determination of venlafaxine (VEN) and its metabolite O-desmethylvenlafaxine (ODV) in rat plasma has been developed and validated using Venlafaxine d6 as the internal standard. The compounds and internal standard were extracted from plasma by solid phase extraction. The UPLC separation of the analytes was performed on ACQUITY UPLC® BEH Shield RP18 (1.7 µm, 100 mm×2.1 mm) column, using isocratic elution with mobile phase constituted of water (containing 2 mM ammonium acetate): acetonitrile (20:80, v/v) at a flow rate of 0.3 mL/min. All of the analytes were eluted within 1.5 min. The compounds were ionized in the electrospray ionization (ESI) ion source of the mass spectrometer, operating in multiple reaction monitoring (MRM) and positive ion mode. The precursor to product ion transitions monitored for VEN, ODV and Venlafaxine d6 were m/z 278.3→121.08, 264.2→107.1 and 284.4→121.0, respectively. The developed and validated method was used for the pharmacokinetic study of VEN in rats.

New chiral reverse phase HPLC method for enantioselective analysis of ketorolac using chiral AGP column.

A simple, specific, precise, sensitive and rapid reverse phase-HPLC method was developed for determination of ketorolac enantiomers, a potent nonnarcotic analgesic in pharmaceutical formulations. The method was developed on a chiral AGP column. Mobile phase was 0.1 M sodium phosphate buffer (pH 4.5): Isopropanol (98:2, v/v), at a flow rate of 1 mL/min with run time of 15 min. Ultraviolet detection was made at 322 nm. The linearity range was 0.02-10 µg/mL for each of the enantiomers. The mobile phase composition was systematically studied to find the optimum chromatographic conditions. Validation of the method under the conditions selected showed that it was selective and precise and that the detector response was linear function of ketorolac.

Assessment of air pollution stress on some commonly grown tree species in industrial zone of Durgapur, West Bengal, India.

The present study deals with the biochemical responses of some selected tree species with respect to increased air pollution in Durgapur industrial city in India. Areas in vicinity to industries possess very high concentrations of suspended particulate matter (571 microg/m3), SOx (132 microg/m3) and NOx (97 microg/m3) which shows significant correlations (p < 0.05) with the biochemical constituents of stressed plants. Plants growing in industrial zone exhibit a considerable decline in total chlorophyll (34.97-59.81%), soluble sugars (23.85-33.16%) and protein content (21.59-47.13%) and increase in ascorbic acid (81.87-238.53%) and proline content (123.47-284.91%). Of the studied tree species, Shorea robusta (9.78 +/- 0.095), Alstonia scholaris (8.76 +/- 0.084), Peltophorum pterocarpum (8.99 +/- 0.13) and Albizia lebbeck (7.71 +/- 0.012) were found to be more tolerant with higher Air Pollution Toblerance Index (APTI) and Tectona grandis (6.13 +/- 0.276), Lagerstroemia speciosa (7.075 +/- 0.18) and Delonix regia (6.87 +/- 0.079) were sensitive with lower APTI values. Therefore, plant species with higher APTI value, being more resistant, can be used as pollutant absorbent to reduce the pollution level and are suitable for plantations in industrial areas.

Temporal changes and depth wise variations in pit pond hydrochemistry contaminated with industrial effluents with special emphasis on metal distribution in water-sediment system.

The investigation showed pronounced temporal and vertical variations of pit lake-water chemistry contaminated with industrial effluents. An intermixing layer of few meters at a depth of 5-8 m usually separates an upper oxic epilimnion with alkaline pH from deeper sub-oxic/anoxic zone with relatively lower pH. Metal concentrations were in higher magnitude at anoxic zone in comparison to surface layer. Most of the parameters including metals showed higher concentrations during summer, while least concentrations were observed during monsoon. In shallow sediments, metals were mainly in insoluble-residual form, while redox metals were fractionated as oxihydroxide-reducible form. Geoaccumulation of metals in bottom sediments were Fe>Cr>Pb>Cu>Cd>Mn>Zn. Toxicity assessment showed that pit pond water is highly contaminated (C(d)=7.52) and moderate pollution load (PLI=2.272) in shallow sediments, with metal evaluation index (HEI) value of 11.08 and 15.91 respectively.

Metal accumulation and its effects in relation to biochemical response of vegetables irrigated with metal contaminated water and wastewater.

Agricultural application of metal contaminated water resulted in elevated concentrations of metals in irrigated soil and vegetables. Metal enrichment in irrigated soil is in the sequence of Cr>Fe>Pb>Mn>Zn>Cu>Cd. High metal translocation was observed from soil to plants with varied accumulation pattern in different species. Fe, Mn, Cu, Zn, Cr showed higher translocation to the aerial parts, while Cd, Pb exhibits their restricted mobility and concentrated in roots and stems. Hyperaccumulation of metals in vegetative parts resulted significant decrease (p<0.05) in total chlorophyll and soluble sugars, with elevated (p<0.05) protein and proline content in cultivated vegetables. Oxidative stress due to high metal concentrations significantly induced (p<0.05) the antioxidant-enzyme activity. Peroxidase (52-206%) and catalase (40-106%) activity was noticeably higher in all the examined species, while enhanced activity of ascorbate peroxidase (70-78%) was observed in pea and spinach.

Rapid and sensitive liquid chromatographic method for determination of Paclitaxel from parenteral formulation and nanoparticles.

A simple and fast reversed phase liquid chromatographic method was developed for estimation of paclitaxel in commercially available parenteral formulation and nanoparticles. Separations were carried out using mobile phase consisting of acetonitrile and 20 mM potassium dihydrogen phosphate (45:55, v/v) on Lichrocart(®) C(18) analytical column at a flow rate of 1 ml/min and detection wavelength of 230 nm. The developed method exhibited linearity over an analytical range of 50-2000 ng/ml with regression equation, mean peak area= 137.58 concentration (ng/ml)+1765.94, (R(2) =0.9999). The method demonstrated selectivity with no interfering peaks eluting near the vicinity of drug peak. The method was found to be sensitive with detection and quantification limits of 7.57 ng/ml and 22.94 ng/ml. The method has shown consistent and good recoveries from parenteral formulation (100.06±0.86%) and nanoparticles (100.43±0.91%). The method was successfully employed for the analysis of in vitro release study samples of nanoparticle formulation. The method was also applied for determination of paclitaxel content in various pharmaceutical formulations.

Oral controlled release formulations of rifampicin. Part II: Effect of formulation variables and process parameters on in vitro release.

Hydrophilic controlled release matrix tablets of rifampicin, a poorly soluble drug, have been formulated using hydroxypropyl methylcellulose (HPMC) polymer (low, medium, and high viscosity) by direct compression method. Influence of formulation variables and process parameters such as drug:HPMC ratio, viscosity grade of HPMC, drug particle size, and compression force on the formulation characters and drug release has been studied. Our results indicated that the release rate of the drug and the mechanism of release from the HPMC matrices are mainly controlled by the drug:HPMC ratio and viscosity grade of the HPMC. In general, decrease in the drug particle size decreased the drug release. Lower viscosity HPMC polymer was found to be more sensitive to the effect of compression force than the higher viscosity. The formulations were found to be stable and reproducible.

Screening of wheat varieties and associated bacterial population in old alluvial soil of Burdwan, West Bengal.

In order to screen out the best variety of wheat (Triticum aestivum) out of eight varieties (viz., HP 1633, BW 11, NW 1014, Sonalika, HUW 468, K 9107, HP 1731 and HUW 234), a field experiment was conducted (from Dec. 2002 to April 2003) in a randomized block design replicated thrice at Crop Research and Seed Multiplication Farm, Burdwan University, West Bengal, India. Various morpho physiological parameters viz., plant population, length of shoot and root, leaf area index (LAI), crop growth rate (CGR), leaf area ratio (LAR), leaf area duration (LAD), net assimilation rate (NAR), yield attributes viz., length of panicles, number of grains per panicle, grain yield, straw yield, pigment content in flag leaf (chlorophyll a, b and total chlorophyll and carotenoid content) were estimated and analyzed statistically Soil bacterial populations were also estimated in the fallow land before sowing of seeds and after harvesting of crop. The HUW 468 variety records higher grain yield, maximum panicle length and maximum chlorophyll b and total chlorophyll content.

New, sensitive and validated spectrofluorimetric method for the estimation of etoposide in bulk and pharmaceutical formulations.

A new, simple and sensitive spectrofluorimetric method was developed for the routine estimation of etoposide, an anticancer drug, in bulk and in pharmaceutical formulations. The medium selected for the estimation of etoposide was methanol : phosphate buffer (pH 7.4) in a ratio of 70 : 30 v/v. Excitation and emission wavelengths used were 240 and 324 nm respectively. The method was validated according to ICH and U.S.P guidelines. Linearity range was 200-1000 ng/ml with detection and quantitation limits of 23 ng/ml and 72 ng/ml respectively. Regression equation obtained was Fluorescence Intensity = 6.704 (Concentration in ng/ml) + 115.4. The drug was found to be stable and there was no interference from the excipients present in different formulations of etoposide.

HATs and HDACs in neurodegeneration: a tale of disconcerted acetylation homeostasis.

Gradual disclosure of the molecular basis of selective neuronal apoptosis during neurodegenerative diseases reveals active participation of acetylating and deacetylating agents during the process. Several studies have now successfully manipulated neuronal vulnerability by influencing the dose and enzymatic activity of histone acetyltransferases (HATs) and histone deacetylases (HDACs), enzymes regulating acetylation homeostasis within the nucleus, thus focusing on the importance of balanced acetylation status in neuronal vitality. It is now increasingly becoming clear that acetylation balance is greatly impaired during neurodegenerative conditions. Herein, we attempt to illuminate molecular means by which such impairment is manifested and how the compromised acetylation homeostasis is intimately coupled to neurodegeneration. Finally, we discuss the therapeutic potential of reinstating the HAT-HDAC balance to ameliorate neurodegenerative diseases.

Design and study of rifampicin oral controlled release formulations.

Oral controlled release formulations of rifampicin have been developed by using hydroxypropyl methylcellulose polymer at different ratios. From in vitro release data, we found that the release was extended with an increase of polymer proportion from 20% to 40%. However, increase in polymer beyond 40% resulted in no significant change in the release rate. There was a distinct difference in the release rate and release character due to variation in the compression force. The release kinetics were analyzed using Ritger and Peppas exponential equation. Stability studies at ambient storage conditions for 1 year showed that formulations were stable.

Determination of celecoxib in pharmaceutical formulations using UV spectrophotometry and liquid chromatography.

A new UV spectrophotometric method (UV method) and a reversed phase liquid chromatographic method (LC method) for the quantitative estimation of celecoxib, a selective COX-2 inhibitor, in pure form and in solid dosage form were developed in the present study. The linear regression equations obtained by least square regression method, were Abs=4.949 x 10(-2).Conc. (in microg/ml)+1.110 x 10(-2) for the UV method and Area under the curve=5.340 x 10(1).Conc. (in ng/ml)+3.144 x 10(2) for the LC method, respectively. The detection limit, as per the error propagation theory, was found to be 0.26 microg/ml and 25 ng/ml, respectively, for the UV and LC methods. The developed methods were employed with a high degree of precision and accuracy for the estimation of total drug content in three commercial capsule formulations of celecoxib. The results of analysis were treated statistically, as per International Conference on Harmonisation (ICH) guidelines for validation of analytical procedures, and by recovery studies. The results were found to be accurate, reproducible and free from interference and better than the earlier reported methods.

Oral controlled release formulation of diclofenac sodium by microencapsulation with ethyl cellulose.

The aim of this study was to formulate and evaluate microencapsulated controlled release preparations of diclofenac sodium (DFS) using different proportions of ethyl cellulose (EC) as the retardant material to extend the release. The formulated microcapsules were then compressed into tablets to obtain controlled release oral formulations. Phase separation-coacervation technique was employed to prepare microcapsules of DFS using different proportions of EC in cyclohexane. Physical characteristics of microcapsules and their tablets, in vitro release pattern of the designed microcapsules and their tablets prepared from them were studied using USP dissolution apparatus (USP 2000) type 2 (paddle method) in triple distilled water. The prepared microcapsules were white, free flowing and spherical in shape, with the particle size varying from 49.94-52.72 microm. The duration of DFS release from microcapsules was found to be directly proportional to the proportion of EC and, thus, coat thickness. All tablets were of good quality with respect to appearance, drug content uniformity, hardness, weight variation, friability and thickness uniformity. In vitro release study of the tabletted microcapsules in triple distilled water showed a zero order release kinetics and extended release beyond 24 h. A good correlation was obtained between drug release (t(60)) and proportion of EC in the microcapsules. In the case of tabletted microcapsules, very good correlation could be established between t(60), proportion of EC, weight of the tablets and between release rate constant (K) and proportion of EC. All the formulations were highly stable and possessed reproducible release kinetics across the batches.

A comparative study of controlled release matrix tablets of diclofenac sodium, ciprofloxacin hydrochloride, and theophylline.

The need for controlled release formulations for diclofenac sodium, ciprofloxacin, and theophylline is well recognized. In our study, controlled release tablets of the three drugs were formulated by the matrix-embedding technique using ethyl cellulose as retardant. Tablets of all the drugs were of good physical quality with respect to appearance, drug content uniformity, hardness, weight variation, and friability. In vitro release rate studies showed that ethyl cellulose extended the release of the three drugs to 12 hr or more. Release patterns from formulations of the three drugs followed Higuchi's square root kinetics. At pH 6.8, the release rate was higher in all three drugs, probably due to increased solubility of the drugs and/or increased swelling of ethyl cellulose at the higher pH. The formulations were highly stable and possessed reproducible release kinetics across batches.