Type III Monteggia Fracture-dislocation with Radial Nerve Injury in Adults - A Case Report of two Cases.

Introduction: Uncommon complication of Monteggia fracture is associated PIN palsy. The PIN palsy following Monteggia fracture-dislocation is neuropraxias and will recover spontaneously. Case Report: Two cases who were diagnosed as Monteggia fracture-dislocation with PIN palsy and associated superficial branch of radial nerve injury - Power 0/5 and sensations 0/2 were taken up for surgery (open reduction internal fixation of fracture of ulna + closed reduction of radial head). By the end of 7 weeks, both sensory and motor power were fully recovered spontaneously in both the cases. Discussion: Most of the PIN injuries following Monteggia fracture-dislocation are neuropraxias and will recover spontaneously after closed reduction of radial head without any intervention to the nerve. The nerve needs to be intervened if there are no signs of recovery by 3 months. The time frame for the nerve to be intervened remains controversial. Conclusion: In both of our cases, the injury is probably proximal to the terminal division of radial nerve and the injuries were neuropraxias and have recovered spontaneously. Hence, we suggest not exploring the nerve in all cases with Monteggia fracture-dislocation immediately even when there is associated sensory deficit.

α-Glucosidase Inhibitory Isomeric Corniculatolides from the Stems of the Indian Mangrove Plant, Xylocarpus granatum.

Three new isomeric corniculatolides (1, 2, and 3) with an unusual caffrane and isocorniculane framework, and five known metabolites were isolated from the chloroform extract of the stems of Xylocarpus granatum. The structures of the new metabolites were deduced as corniculatolide B (1), isocorniculatolide B (2), and corniculatolide C (3) by spectroscopic data analysis and a combination of chemical transformations and supported by single-crystal X-ray crystallographic data of 1 and 3. The isolated compounds were evaluated for their in vitro cytotoxicity and α-glucosidase (Saccharomyces cerevisiae) inhibitory potential. Compound 3 possessed α-glucosidase inhibitory activity with an IC50 value of 24.8 µM, whereas these rare macrolides showed no effect on the mammalian cancer cell lines MIAPaCa-2, DU145, MCF-7, and HTC-116.

Synthesis of novel pyrazolo[3,4-b]quinolinyl acetamide analogs, their evaluation for antimicrobial and anticancer activities, validation by molecular modeling and CoMFA analysis.

A series of novel alkyl amide functionalized 2,3-pyrazole fused quinoline derivatives 5, 6 and 7 have been prepared starting from quinoline-2(1H)one 1 in a series of steps. All the final products were screened for antibacterial activity, the promising lead compound 5r was identified with MIC values ranging between 3.9 and 7.8 µg/mL against different bacterial strains. Compound 5r also showed good antifungal and anti-biofilm activities against the tested panel of various fungal and bacterial strains. Compound 5r when treated on mature biofilms of S. aureus strain MLS16, showed increased levels of intracellular ROS accumulation suggesting its contribution to the bactericidal activity. All the compounds were also screened for anticancer activity against a panel of four human cancer cell lines. Based on these studies, compounds 5c, 5d, 5r and 7f were considered as promising and exhibited significant cytotoxicity with IC50 values of <15 µM. The biological activity data was further validated by molecular modeling and CoMFA studies.

Self-assembly, optical, thermal and electrochemical properties of bis-N-benzyl perylene diimide dye.

Flexible methylene containing N,N'-bis-(benzyl)-3,4,9,10-perylenebis(dicarboximide) (1) was synthesized. Self-assembled microstructures (hollow tubes, average length and width: 7.7 and 0.8 µm) of 1 were also prepared (T-1). Comparative studies of the optical, thermal and electrochemical properties of 1 and T-1 have been extensively carried out. The T-1 hallow tubes have shown extremely broad absorption in the near-infrared (300-800 nm) region (NIR) even in solution and intensified conductivity in the solid-state compared to 1. Under daylight and a UV lamp (365 nm), the emission colors of 1 are uniform pink and fluorescent yellow, respectively. Under the same conditions the colors of T-1 change to deep brown and glowing red, respectively. Two different isopotential points obtained through CV scans for 1 indicate the presence of two interconvertible chromophores within the system. The results clearly indicate that the anodic and cathodic processes are extremely intensified in the self-assembled T-1 structure.

Modelling nitrous oxide emissions from mown-grass and grain-cropping systems: Testing and sensitivity analysis of DailyDayCent using high frequency measurements.

The DailyDayCent biogeochemical model was used to simulate nitrous oxide (N2O) emissions from two contrasting agro-ecosystems viz. a mown-grassland and a grain-cropping system in France. Model performance was tested using high frequency measurements over three years; additionally a local sensitivity analysis was performed. Annual N2O emissions of 1.97 and 1.24kgNha-1year-1 were simulated from mown-grassland and grain-cropland, respectively. Measured and simulated water filled pore space (r=0.86, ME=-2.5%) and soil temperature (r=0.96, ME=-0.63°C) at 10cm soil depth matched well in mown-grassland. The model predicted cumulative hay and crop production effectively. The model simulated soil mineral nitrogen (N) concentrations, particularly ammonium (NH4+), reasonably, but the model significantly underestimated soil nitrate (NO3-) concentration under both systems. In general, the model effectively simulated the dynamics and the magnitude of daily N2O flux over the whole experimental period in grain-cropland (r=0.16, ME=-0.81gNha-1day-1), with reasonable agreement between measured and modelled N2O fluxes for the mown-grassland (r=0.63, ME=-0.65gNha-1day-1). Our results indicate that DailyDayCent has potential for use as a tool for predicting overall N2O emissions in the study region. However, in-depth analysis shows some systematic discrepancies between measured and simulated N2O fluxes on a daily basis. The current exercise suggests that the DailyDayCent may need improvement, particularly the sub-module responsible for N transformations, for better simulating soil mineral N, especially soil NO3- concentration, and N2O flux on a daily basis. The sensitivity analysis shows that many factors such as climate change, N-fertilizer use, input uncertainty and parameter value could influence the simulation of N2O emissions. Sensitivity estimation also helped to identify critical parameters, which need careful estimation or site-specific calibration for successful modelling of N2O emissions in the study region.

Synthesis of dihydrosterculic acid-based monoglucosyl diacylglycerol and its analogues and their biological evaluation.

In the present study, Lactobacillus plantarum glycolipid (GL1) molecule in ß-configuration and its fatty acid analogues were synthesized using trichloroacetimidate methodology. The ß-configuration of the GL1 molecule was unambiguously assigned by NMR studies using 2D-ROESY (NOE) and J-coupling analysis. Dihydrosterculic acid was synthesized using Furukawa's reagent and the selective esterification of dihydrosterculic acid at C-3 position of glycerol was achieved with EDC-HCl at 0 °C. In vitro cytotoxicity of the GL1 molecule and its fatty acid analogues was evaluated against DU145, A549, SKOV3 and MCF7 cell lines. Among all the synthesized molecules, the GL1 molecule and compound 7d showed moderate activity, while the compound 7b showed promising activity against all the tested cell lines with IC50 values of 20.1, 18.2, 19.1 and 17.6 µM, respectively. In addition, all tested compounds showed poor cytotoxicity against normal HUVEC cells. The MCF7 cells when treated with compound 7b showed lower bromodeoxyuridine incorporation levels as compared to untreated cells, suggesting that the compound 7b was highly effective and inhibited the cell proliferation. In addition, the compounds showed significant increase in caspases 3 and 9 levels by inducing apoptosis in MCF 7 cells.

Novel cycloartane triterpenoids from the Nepal native plant Caragana sukiensis.

A phytochemical study on the arial part of Caragana sukiensis resulted in the isolation of three new cycloartane triterpenoids 1-3 and their structures were fully established on the basis of detailed spectroscopic (especially 2D NMR and Mass) analysis. These new compounds possessed hemiacetal fused tetrahydropyran rings at C-15/C-16, while 2 and 3 also contains d-xylose moiety.

Synthesis of novel amide functionalized 2H-chromene derivatives by Ritter amidation of primary alcohol using HBF4·OEt2 as a mild and versatile reagent and evaluation of their antimicrobial and anti-biofilm activities.

A series of novel amide functionalized 2H-chromene derivatives 3 were prepared starting from ethyl-2-hydroxy-2-(trifluoromethyl)-2H-chromene-3-carboxylate 1 via sodium borohydride reduction followed by Ritter amidation using HBF4·OEt2 as a mild and versatile reagent. All the products 3 were screened for antimicrobial activity against various Gram-positive, Gram-negative bacteria and fungal strain. The promising derivatives such as 3f, 3g, 3k, 3l, 3m, 3n and 3o were further screened for minimum bactericidal concentration and bio-film inhibition activity and identified the potential ones. Among all the promising, compound 3g was more potent for antimicrobial, MBC and anti bio-film activities. The structure verses activity relationship of 3g revealed that the presence of two bromine atoms at sixth and R position promotes high activity.

Stereoselective synthesis of spiro[tetrahydropyran-3,3'-oxindole] derivatives employing Prins cascade strategy.

A variety of aldehydes undergo smooth coupling with 4-hydroxy-N-methyl-2-methylene-N-phenylbutanamide in the presence of BF3·OEt2 under ambient conditions to produce the corresponding spiro-oxindole derivatives in good yields with excellent selectivity. It is an entirely new strategy to construct the spirocycles in a one-pot operation through a Prins cascade process.

Synthesis of a novel fluorescent amphiphilic chitosan biopolymer: photophysical and electrochemical behavior.

The present investigation describes for the first time, the synthesis and detailed characterization of a novel fluorescent and amphiphilic chitosan polymer (3) containing fluorescent peryleneimide chromophores for biomedical applications. The polymer 3 is moderately soluble in a wide range of organic solvents and aqueous solutions, unlike chitosan (2). The Mw of 3 and 2 determined by GPC were 467 kDa and 460 kDa, respectively. The photophysical and electrochemical properties measured in solution and solid states are engrossing. is soluble in the entire pH range and exhibits excimer emission above pH 5. In solution, 3 is electroactive but 2 is not. Whereas in the solid-state, 3 shows one quasi-reversible oxidation and reversible reduction step and 2 exhibits only one quasi-reversible oxidation step. Our results point out a new class of organic biopolymers that could yield promising potentials in many biomedical applications.

Development and validation of highly selective and robust method for simultaneous estimation of pioglitazone, hydroxypioglitazone and metformin in human plasma by LC-MS/MS: application to a pharmacokinetic study.

A simple, selective and robust reverse phase high performance liquid chromatography-electrospray ionization-tandem mass spectrometry (ESI-MS/MS) method for simultaneous quantitation of pioglitazone (PIO), pioglitazone metabolite M-IV - hydroxypioglitazone (OH-PIO) and metformin (MET) in human plasma using deuterated internal standards (IS) is developed and fully validated as per industrial practices. After acetonitrile-induced protein precipitation of the plasma samples; PIO, OH-PIO, MET and IS were chromatographed on reverse phase column and analyzed in the multiple reaction monitoring in positive ion mode. The ion transitions were monitored at m/z 357.2→134.2 for PIO, 373.0→150.1 for OH-PIO, 130.2→71.0 for MET, 361.1→134.2 for PIO-IS and 136.1→77.1 for MET-IS. The total chromatographic run time was 4.0min. A linear response function (r>0.998) was established for the range of concentrations 15-2500ng/mL, 10-1500ng/mL and 25-3000ng/mL for PIO, OH-PIO and MET respectively in human plasma. The intra and inter-day precision and accuracy values have met the set acceptance criteria. The method is simple, selective, robust economic and has been applied successfully to more than 2000 plasma samples as part of pharmacokinetic study in humans.

Development and validation of a highly sensitive LC-MS/MS method for quantitation of dexlansoprazole in human plasma: application to a human pharmacokinetic study.

A highly sensitive, specific and simple LC-MS/MS method was developed for the simultaneous estimation of dexlansoprazole (DEX) with 50 µL of human plasma using omeprazole as an internal standard (IS). The API-4000 LC-MS/MS was operated under multiple reaction-monitoring mode using electrospray ionization. A simple liquid-liquid extraction process was used to extract DEX and IS from human plasma. The total run time was 2.00 min and the elution of DEX and IS occurred at 1.20 min. This was achieved with a mobile phase consisting of 0.2% ammonia-acetonitrile (20:80, v/v) at a flow rate of 0.50 mL/min on an X-terra RP 18 (50 × 4.6 mm, 5 µm) column. The developed method was validated in human plasma with a lower limit of quantitation of 2 ng/mL for DEX. A linear response function was established for the range of concentrations 2.00-2500.0 ng/mL (r > 0.998) for DEX. The intra- and inter-day precision values for DEX met the acceptance criteria as per FDA guidelines. DEX was stable in the battery of stability studies, viz. bench-top, auto-sampler and freeze-thaw cycles. The developed assay method was applied to an oral bioequivalence study in humans.

A rapid LC-MS/MS method for quantitation of eszopiclone in human plasma: application to a human pharmacokinetic study.

A highly reproducible, specific and cost-effective LC-MS/MS method was developed for simultaneous estimation of eszopiclone (ESZ) with 50 µL of human plasma using paroxetine as an internal standard (IS). The API-4000 LC-MS/MS was operated under the multiple reaction-monitoring mode using the electrospray ionization technique. A simple liquid-liquid extraction process was used to extract ESZ and IS from human plasma. The total run time was 1.5 min and the elution of ESZ and IS occurred at 0.90 min; this was achieved with a mobile phase consisting of 0.1% formic acid-methanol (15:85, v/v) at a flow rate of 0.50 mL/min on a Discover C(18) (50 × 4.6 mm, 5 µm) column. The developed method was validated in human plasma with a lower limit of quantitation of 0.1 ng/mL for ESZ. A linear response function was established for the range of concentrations 0.10-120 ng/mL (r > 0.998) for ESZ. The intra- and inter-day precision values for ESZ were acceptable as per FDA guidelines. Eszopiclone was stable in the battery of stability studies, viz. bench-top, autosampler and freeze-thaw cycles. The developed assay method was applied to an oral bioequivalence study in humans.

Systems approaches in global change and biogeochemistry research.

Systems approaches have great potential for application in predictive ecology. In this paper, we present a range of examples, where systems approaches are being developed and applied at a range of scales in the field of global change and biogeochemical cycling. Systems approaches range from Bayesian calibration techniques at plot scale, through data assimilation methods at regional to continental scales, to multi-disciplinary numerical model applications at country to global scales. We provide examples from a range of studies and show how these approaches are being used to address current topics in global change and biogeochemical research, such as the interaction between carbon and nitrogen cycles, terrestrial carbon feedbacks to climate change and the attribution of observed global changes to various drivers of change. We examine how transferable the methods and techniques might be to other areas of ecosystem science and ecology.

Development and validation of highly sensitive method for determination of misoprostol free acid in human plasma by liquid chromatography-electrospray ionization tandem mass spectrometry: application to a clinical pharmacokinetic study.

A highly sensitive, selective and evaporation free SPE extraction, ESI-LC-MS/MS method has been developed for estimation of misoprostol free acid in human plasma using misoprostol acid-d(5) as an internal standard (IS). The analyte was separated using isocratic mobile phase on reverse phase column and analyzed by MS/MS in the multiple reaction monitoring mode using the respective [M-H] anions, m/z 367-249 for misoprostol acid and m/z 372-249 for the IS. The total run time was 5.0 min and the elution of misoprostol acid and misoprostol acid-d(5) (IS) occurred at 3.6 min. The developed method was validated in human plasma with a lower limit of quantification of 2.5 pg/mL. A linear response function was established for the range of concentrations 2.5-1200 pg/mL (r>0.998) for misoprostol acid in human plasma. The intra and inter-day precision values for misoprostol acid met the acceptance as per FDA guidelines. Misoprostol acid was stable in the battery of stability studies viz., bench-top, auto-sampler and freeze/thaw cycles. The developed assay method was applied to an oral pharmacokinetic study in humans.

A new tunable light-emitting and π-stacked hexa-ethyleneglycol naphthalene-bisimide oligomer: synthesis, photophysics and electrochemical properties.

An oligomer (3) containing flexible hydrophilic hexa(ethylene glycol) and hydrophobic naphthalene-bisimide chromophores has been synthesized by a one-step condensation reaction and its photophysical and electrochemical properties were investigated. 3 was characterized through the data from NMR, IR, UV-vis, GPC, DSC, TGA, elemental analysis and cyclic voltammetry. The average molecular weight (M(w)) of 3 was 4430 g mol(-1). Intrinsic viscosity was measured as 0.28 dL g(-1) in m-cresol at 25 °C. It has high thermal stability (T(d) = 325 °C). Interestingly, compound 3 shows excimer-like emission in all kinds of solvents. The band gap energy (E(g)), LUMO and HOMO energy values in nonpolar and polar protic solvents were 2.71 eV/3.12 eV, -3.69 eV/-3.88 eV and -6.40 eV/-7.00 eV for 3, respectively. The oligomer showed concentration and solvent dependent fluorescent color tunability. Remarkably, the fluorescent colors of the excimer emissions at 10(-6) M concentration in CHCl(3), DMF and MeOH are light yellow, light blue-yellow and strong blue, respectively, and become more intense at higher concentrations. The excimer emission color in CHCl(3) and DMF is fluorescent yellow and changed to green in MeOH at 10(-4) M concentration. 3 shows two reversible reduction steps at -1.103 and -1.457 V (vs. ferrocene/ferrocenium) in nonpolar solvent CH(2)Cl(2) and only one at -0.917 V in (50:50) CH(3)OH-CH(3)CN binary solvent mixture with higher reversibility. Strong blue-shifts of emission band were noted in protic solvents, which confirm the existence of a negative solvatochromism probably due to protonation. The strong solvent-dependent photophysical and electrochemical properties, including the large shift of excimer emission maximum reflecting self-assembly mediated through hydrogen bonding and π-stacking interactions, make the oligomer a potential candidate for various photo-sensing applications.

Development and validation of a highly sensitive LC-MS/MS method for simultaneous quantitation of nortriptyline and 10-hydroxynortriptyline in human plasma: application to a human pharmacokinetic study.

A highly sensitive and specific LC-MS/MS method has been developed for simultaneous estimation of nortriptyline (NTP) and 10-hydroxynortriptyline (OH-NTP) in human plasma (250 µL) using carbamazepine as an internal standard (IS). LC-MS/MS was operated under the multiple reaction-monitoring mode using the electrospray ionization technique. A simple liquid-liquid extraction process was used to extract NTP, OH-NTP and IS from human plasma. The total run time was 2.5 min and the elution of NTP, OH-NTP and IS occurred at 1.44, 1.28 and 1.39 min, respectively; this was achieved with a mobile phase consisting of 20 mm ammonium acetate : acetonitrile (20:80, v/v) at a flow rate of 0.50 mL/min on a HyPURITY C(18) column. The developed method was validated in human plasma with a lower limit of quantitation of 1.09 ng/mL for both NTP and OH-NTP. A linear response function was established for the range of concentrations 1.09-30.0 ng/mL (r > 0.998) for both NTP and OH-NTP. The intra- and inter-day precision values for NTP and OH-NTP met the acceptance as per FDA guidelines. NTP and OH-NTP were stable in a battery of stability studies, i.e. bench-top, auto-sampler and freeze-thaw cycles. The developed assay was applied to a pharmacokinetic study in humans.

Gas-liquid chromatography for fenvalerate residue analysis: in vivo alterations in the acetylcholinesterase activity and acetylcholine in different tissues of the fish, Labeo rohita (Hamilton).

The disruption of acetylcholinesterase activity (AChE) in the freshwater fish, Labeo rohita is demonstrated in the present study using acetylthiocholine iodide as substrate. L. rohita on exposure to lethal (6 microg/L) and sub-lethal (0.75 microg/L) concentrations of fenvalerate showed time- and dose-dependent inhibition in the activity of AChE, suggesting a decrease in the cholinergic transmission and consequent accumulation of acetylcholine (ACh) in the tissues (brain, gill, liver, and muscle) leading to continuous nerve impulses, causing prolonged muscle contraction which, as a consequence, causes paralysis and results in death. These also have lead to behavioral changes and create widespread disturbance in the normal neural physiology of the fish. Residue analysis using a gas-liquid chromatography technique (GLC) revealed that highest quantity of fenvalerate accumulated in gill followed by liver and muscle under lethal concentrations, whereas in sub-lethal concentrations muscle accumulated the highest concentration followed by gill and liver. The results suggest that in a biomonitoring program AChE activity can be a good diagnostic tool for assessing fenvalerate toxicity. The lipophilic nature of fenvalerate is of concern, since L. rohita is an important staple fish species, which may lead to the phenomenon of biomagnification.

Simultaneous estimation of four proton pump inhibitors--lansoprazole, omeprazole, pantoprazole and rabeprazole: development of a novel generic HPLC-UV method and its application to clinical pharmacokinetic study.

A highly selective, sensitive and accurate HPLC method has been developed and validated for the estimation of four proton-pump inhibitors (PPI), lansoprazole (LPZ), omeprazole (OPZ), pantoprazole (PPZ) and rabeprazole (RPZ), with 500 microL human plasma using zonisamide as an internal standard (IS). The sample preparation involved simple liquid-liquid extraction of LPZ, OPZ, PPZ and RPZ and IS from human plasma with ethyl acetate. The baseline separation of all the peaks was achieved with 0.1% triethylamine (pH 6.0):acetonitrile (72:28, v/v) at a flow rate of 1 mL/min on a Zorbax C(8) column. The total chromatographic run time was 11.0 min and the simultaneous elution of IS, OPZ, RPZ, PPZ and LPZ occurred at approximately 2.42, 4.45, 5.02 and 9.37 min, respectively. The method was proved to be accurate and precise at linearity range of 20.61-1999.79 ng/mL with a correlation coefficient (r) of >or=0.999. The limit of quantitation for each of the PPI studied was 20.61 ng/mL. The intra- and inter-day precision and accuracy values were found to be within the assay variability limits as per the FDA guidelines. The developed assay method was applied to a pharmacokinetic study in human volunteers.

Quantification of montelukast, a selective cysteinyl leukotriene receptor (CysLT1) antagonist in human plasma by liquid chromatography-mass spectrometry: validation and its application to a human pharmacokinetic study.

A highly sensitive, rapid assay method has been developed and validated for the estimation of montelukast (MTK) in human plasma with liquid chromatography coupled to tandem mass spectrometry with electro spray ionization in the positive-ion mode. Liquid-liquid extraction was used to extract MTK and amlodipine (internal standard, IS) from human plasma. Chromatographic separation was achieved with 10 mM ammonium acetate (pH 6.4): acetonitrile (15:85, v/v) at a flow rate of 0.50 mL/min on a Discovery HS C(18) column with a total run time of 3.5 min. The MS/MS ion transitions monitored were 586.10 --> 422.10 for MTK and 409.20 --> 238.30 for IS. Method validation and clinical sample analysis were performed as per FDA guidelines and the results met the acceptance criteria. The lower limit of quantitation achieved was 0.25 ng/mL and linearity was observed from 0.25 to 800 ng/mL. The intra-day and inter-day precisions were 5.97-8.33 and 7.09-10.13%, respectively. This novel method has been applied to a pharmacokinetic study of MTK in humans.