Outcome of tailored therapy in rheumatic heart disease with persistent atrial fibrillation (RHD-AF).

INTRODUCTION: Rheumatic heart disease with persistent atrial fibrillation (RHD-AF) is associated with increased morbidity. However, there is no standardized approach for the maintenance of sinus rhythm (SR) in them. We aimed to determine the utility of a stepwise approach to achieve SR in RHD-AF. METHODS: Consecutive patients with RHD-AF from July 2021 to August 2023 formed the study cohort. The stepwise approach included pharmacological rhythm control and/or electrical cardioversion (Central illustration). In patients with recurrence, additional options included AF ablation or pace and ablate strategy with conduction system pacing or biventricular pacing. Clinical improvement, NT-proBNP, 6-Minute Walk Test (6MWT), heart failure (HF) hospitalizations, and thromboembolic complications were documented during follow-up. RESULTS: Eighty-three patients with RHD-AF (mean age 56.13 ± 9.51 years, women 72.28%) were included. Utilizing this approach, 43 (51.81%) achieved and maintained SR during the study period of 11.04 ± 7.14 months. These patients had improved functional class, lower NT-proBNP, better distance covered for 6MWT, and reduced HF hospitalizations. The duration of AF was shorter in patients who achieved SR, compared to those who remained in AF (3.15 ± 1.29 vs 6.93 ± 5.23, p = 0.041). Thirty-five percent (29) maintained SR after a single cardioversion over the study period. Only one underwent AF ablation. Of the 24 who underwent pace and ablate strategy, atrial lead was implanted in 22 (hybrid approach), and 50% of these achieved and maintained SR. Among these 24, none had HF hospitalizations, but patients who maintained SR had further improvement in clinical and functional parameters. CONCLUSIONS: RHD-AF patients who could achieve SR with a stepwise approach, had better clinical outcomes and lower HF hospitalizations.

IgG4 related disease and aortitis: an up-to-date review.

Aortic involvement in immunoglobulin G4-related disease (IgG4-RD) is extremely rare and is often overlooked during the aortitis work-up. IgG4-related aortitis differs from non-IgG4-related aortitis in its histopathological features, site of involvement, laboratory markers, and treatment options. The histopathological examination of the vessel walls characteristically reveals adventitial thickening with intimal sparing, typically affecting the infrarenal abdominal aorta. In addition, inadequate knowledge about the disease often leads to delayed or missed diagnosis and undermanagement of a potentially treatable condition. Hence, in this paper, we review the unique clinical manifestations, laboratory markers, diagnostic features, current treatment strategies, and novel experimental therapeutic options in the management of IgG4-related aortitis.

Optical, emission, and excitation dynamics of Eu3+ -doped bismuth-based phosphate glass for visible display laser applications.

Eu3+ -doped-bismuth-based phosphate glasses with chemical equation (60 - x)P2 O5 -20Bi2 O3 -10Na2 CO3 -10SrF2 -xEu2 O3 (PBNSEu), (where x = 0, 0.1, 0.5, 1.0, 1.5 and 2 mol%) were fabricated using the melt-quenching method. Obtain X-ray diffraction (XRD), energy-dispersive X-ray (EDAX), and Fourier transform infrared (FTIR) spectra were used to characterize the structure of the prepared PBNSEu glass. The J-O (Judd-Ofelt) intensity parameters (Ω2 , Ω4 ) were estimated using photoluminescence emission spectra. When excited with a xenon lamp at λexc  = 394 nm, the most intense red-emission transition occurred at ~612 nm (5 D0 →7 F2 ). J-O intensity parameters were used to calculate radiative properties, whereas the radiative branching ratio (ßR ), radiative transition probability (AR ), radiative lifetime (τR ), and total radiative transition rate (Aτ ) were calculated for the transitions 5 D0 →7 FJ (where J = 0-4) and were obtained in the emission spectra for europium ion-doped in the current glass. Using the CIE1931 chromaticity coordinates axes, the colours of various concentrations of Eu3+ ion-doped PBNS glass were evaluated using the emission spectra. Temperature-dependent luminescence spectra were recorded for the optimized PBNSEu20 glass to calculate the activation energy. These results strongly suggested red components in w-LEDs and visible display laser applications.

Benzo[a]phenoxazinium chlorides: Synthesis, antifungal activity, in silico studies and evaluation as fluorescent probes.

Four new benzo[a]phenoxazinium chlorides with combinations of chloride, ethyl ester and methyl as terminals of the amino substituents were synthesized. These compounds were characterized and their optical properties were studied in absolute dry ethanol and water. Their antiproliferative activity was tested against Saccharomyces cerevisiae in a broth microdilution assay, along with an array of 36 other benzo[a]phenoxazinium chlorides. Minimum Inhibitory Concentration (MIC) values between 1.56 and >200 µM were observed. Fluorescence microscopy studies, used to assess the intracellular distribution of the dyes, showed that these benzo[a]phenoxazinium chlorides function as efficient and site specific probes for the detection of the vacuole membrane. The added advantage of some of the compounds, that displayed the lower MIC values, was the simultaneous staining of both the vacuole membrane and the perinuclear membrane of endoplasmic reticulum (ER). Molecular docking studies were performed on the human membrane protein oxidosqualene cyclase (OSC), using the crystal structure available on PDB (code 1W6K). The results showed that these most active compounds accommodated better in the active sites of ER enzyme OSC suggesting this enzyme as a potential target. As a whole, the results demonstrate that the benzo[a]phenoxazinium chlorides are interesting alternatives to the available commercial dyes. Changes in the substituents of these compounds can tailor both their staining specificity and antimicrobial activity.

Study of trivalent samarium ion embedded lithium-based borate glass for high-density optical memory devices.

Sm3+ ions doped strontium lithium lead borate glasses (SLLB:Sm) were prepared using a conventional melt-quenching technique. The glasses were analyzed using X-ray diffractometry and Fourier transform infrared spectroscopy, optical absorption, fluorescence spectral analysis, and fluorescence lifetime decay. The Judd-Ofelt (J-O) parameters and radiative parameters of the SLLB:Sm10 glass (1.0 mol% Sm3+ ion-doped glass) were calculated using J-O theory. From the emission spectra, among all the synthesized glass, SLLB:Sm10 glass had the highest emission intensity for 4 G5/2 →6 H11/2 transition (610 nm). Emission parameters, such as stimulated emission cross-section and optical gain bandwidth, were calculated. For all concentrations of Sm3+ ions, the decay profile showed an exponential nature and decreased when the Sm3+ ion concentration was increased due to a concentration quenching effect. This result suggests that the synthesized SLLB:Sm10 glass could be used for application in high-density optical memory devices.

Liquid chromatography/electrospray ionization tandem mass spectrometry study of repaglinide and its forced degradation products.

RATIONALE: Stress stability studies of drugs have been recognized as an essential part of the drug development process. These studies are used to investigate the intrinsic stability of the drugs and for the development of a selective stability indicating assay method (SIAM). Stress testing is also useful for the formulation and packaging development, shelf-life determination and designing of manufacturing processes. As per regulatory guidelines, stress degradation studies and structural characterization should be carried out to establish degradation pathways of the drug, which is essential from both the efficacy and safety point of view. As the stress stability studies of repaglinide have not been reported in the literature, the present study has been undertaken. METHODS: Repaglinide (RP), an oral anti-diabetic drug, was subjected to hydrolysis (acidic, alkaline and neutral), oxidation, photolysis and thermal stress conditions as per International Conference on Harmonization (ICH) guidelines Q1A (R2). The chromatographic separation of the drug and its degradation products (DPs) was achieved on an Agilent XDB C-18 column using the gradient elution method with a mobile phase consisting of 20 mM ammonium acetate and acetonitrile at flow rate of 1.0 mL min-1 . The DPs were characterized using liquid chromatography/electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS) in combination with accurate mass measurements. RESULTS: The drug degraded under hydrolytic and oxidative stress, while it was stable under thermal and photolytic stress conditions. In total, six DPs were formed and the LC/MS method described here can resolve all DPs from the parent as well as from each other under various stress conditions. To elucidate the structures of DPs, fragmentation of the [M + H]+ ions of RP and its DPs was studied by using LC/ESI-MS/MS combined with accurate mass measurements. CONCLUSIONS: The forced degradation of RP carried out as per ICH guidelines results in the formation of six degradation products which have been characterized using LC/MS/MS in combination with accurate mass measurements.

Lasing transition at 1.06 µm emission in Nd3+ -doped borate-based tellurium calcium zinc niobium oxide glasses for high-power solid-state lasers.

The spectroscopic properties of Tellurium Calcium Zinc Niobium oxide Borate (TCZNB) glasses of composition (in mol%) 10TeO2  + 15CaO + 5ZnO + 10 Nb2 O5  + (60 - x)B2 O3  + Nd2 O3 (x = 0.1, 0.5, 1.0 or 1.5 mol%) have been investigated experimentally. The three phenomenological intensity parameters Ω2 , Ω4, Ω6 have been calculated using the Judd-Ofelt theory and in turn radiative properties such as radiative transition probabilities, emission cross-sections, branching ratios and radiative lifetimes have been estimated. The trend found in the JO intensity parameter is Ω2  > Ω6  > Ω4 If Ω6  > Ω4 , the glass system is favourable for the laser emission 4 F3/2  â†’ 4 I11/2 in the infrared (IR) wavelength. The experimental values of branching ratio of 4 F3/2  â†’ 4 I11/2 transition indicate favourable lasing action with low threshold power. The evaluated total radiative transition probabilities (AT ), stimulated emission cross-section (σe ) and gain bandwidth parameters (σe  × Δλp ) were compared with earlier reports. An energy level analysis has been carried out considering the experimental energy positions of the absorption and emission bands.

An efficient orange-red-emitting LiNa3 P2 O7 :Sm3+ pyrophosphate: Structural and optical analysis for solid-state lighting.

A trivalent rare-earth ion (Sm3+ )-doped LiNa3 P2 O7 (LNPO) phosphor was synthesized using a conventional high-temperature solid-state reaction route. A predominant orthorhombic phase of LNPO was observed in all X-ray diffraction patterns. The surface states of the LNPO:Sm phosphor were confirmed by X-ray photoelectron spectroscopy. Under 401 nm excitation, the Sm-doped LNPO phosphors showed sharp emission peaks at 563, 600 and 647 nm that are related to the f-f transition of Sm3+ ions. The optimum concentration of Sm3+ (9 mol%) produced Commission Internationale de l'Eclairage chromaticity coordinates, color rendering index and correlated color temperature of (0.564, 0.434), 42 and 1843 K, respectively.

Bacopa monniera Stabilized Silver Nanoparticles Attenuates Oxidative Stress Induced by Aluminum in Albino Mice.

In the recent years usage of nanomedicine plays a promising strategy in the improvement of medical treatment. The ecofriendly synthesized silver nanoparticles has introduced a new opportunity to increase the efficacy of drug by reducing its side effects. In the present study, we investigated the antioxidant property of Bacopa monniera stabilized silver nanoparticles against aluminum induced toxicity in albino mice. Forty male albino mice were randomly divided into five groups. First group was treated as control, second group received aluminum acetate (5 mg/kg b . w), third group received Bacopa monniera extract (5 mg/kg b . w), fourth group received BmSNPs (5 mg/kg b . w), fifth group received aluminum acetate plus BmSNPs. Exposure to aluminum acetate significantly increased lipid peroxidation levels with a significant decrease in the antioxidant enzymes such as superoxide dismutase, catalase and glutathione peroxidase activities in the brain, liver and kidney of mice. Degenerative changes were also observed in brain, liver and kidney of aluminum treated mice. No significant changes in the oxidative stress were observed in the Bacopa monniera and BmSNPs alone treated mice. Whereas, co-administration of BmSNPs to Al treated mice showed a significant decrease in lipid peroxidation levels with a significant increase of SOD, CAT and GPx indicating the antioxidant potential of nanoparticles and in counteracting Al induced oxidative stress and histological response in male albino mice. These findings clearly implicate that BmSNPs are able to eradicate the oxidative stress and prevent the tissue damage in aluminum exposed mice.

Biogenic Preparation of Gold Nanostructures Reduced from Piper longum Leaf Broth and Their Electrochemical Studies.

Exploitation of green chemical procedures for the synthesis of metal nanoparticles by biological process has received great attention in the field of nanotechnology. To demonstrate a biogenic method that involves the reduction of aqueous gold ions by the extract of Piper longum leaves leading to the formation of different morphological gold nanoparticles (AuNPs). The formation of gold nano-structures has been characterized by UV-Vis absorption spectroscopy. The X-ray diffraction (XRD) and selected area electron diffraction (SAED) patterns indicates the AuNPs are highly crystalline nature with the face-centered cubic (111), (200), (220) and (311) facets, respectively. The AuNPs have different sizes and morphologies that are identified by TEM studies. The involvement of water soluble bio-molecules such as carboxylic acids, flavonoids, proteins and terpenoids were identified by Fourier transform infrared (FT-IR) and Raman spectrum. The responsible mechanism of improving acidic nature and the process of encapsulation of gold nanoparticles by Piper longum extract was discussed. Additionally, we have demonstrated the modified carbon paste electrode using gold nanoparticles by means of cyclic voltammetry in a solution of 1 M KCI and 1 mM [Fe(CN)6]3-/4-. The analysis of cyclic voltammetry shows electronic transmission rate between modified Au-CPE and Bare-CPE electrode increased.

Liquid chromatography electrospray ionization tandem mass spectrometry study of nilutamide and its stress degradation products: in silico toxicity prediction of degradation products.

Nilutamide, a nonsteroidal anti-androgen drug, widely used in the treatment of prostate cancer, was subjected to hydrolytic, photolytic, thermal and oxidative stress conditions as per International Conference on Harmonization guidelines Q1A (R2). Nilutamide showed significant degradation under basic hydrolysis and photolytic stress conditions, while it was stable to neutral, acidic and thermal stress conditions. Five degradation products were formed and the chromatographic separation of nilutamide and its degradation products was achieved on a Waters C18 column (4.6 × 250 mm, 5 µm) using a mobile phase consisting of acetonitrile and 0.1% of formic acid in an isocratic elution method. All these degradation products were characterized by LC/MS/MS in negative ion mode, combined with accurate mass measurements. To assign likely structures for the observed degradation products, the fragmentation patterns of the deprotonated drug and its degradation products were compared. The in silico toxicity of the drug and its degradation products was also assessed using TOPKAT software. The carcinogenicity probability of the degradation products, DP-I-IV, was greater than that of nilutamide.

Investigations on anticancer activity of Eu3+ doped hydroxyapatite nanocomposites against MCF7 and 4T1 breast cancer cell lines: A structural and luminescence Perspective.

Breast cancer remains a significant global health concern, necessitating the development of novel therapeutic approaches. In this study, we investigate the role of Eu3+ doped hydroxyapatite nanocomposites (Han: Eu3+) in the treatment of MCF7 and 4T1 breast cancer cell lines. Furthermore, we explored the structural and luminescent properties of these nanocomposites. Han: Eu3+ were synthesized using a modified co-precipitation method, and their morphology and crystal structure were characterized using scanning electron microscopy (SEM) and X-ray diffraction (XRD) in which the average crystalline size of Han: Eu3+ was found to be 25 nm, rendering them suitable for cellular uptake and targeted therapy. To gain insights into the luminescent properties of Han: Eu3+, their excitation and emission spectra were recorded using photoluminescence spectrometer. The characteristic red emission of Eu3+ ions was observed upon excitation, validating the successful doping of Eu3+ into the Han lattice, which was confirmed by the CIE chromaticity coordinate study. These luminescent properties of Han: Eu3+ hold promise for potential applications in bioimaging. To evaluate the efficacy of Han: Eu3+ in breast cancer treatment, MCF7 and 4T1 cell lines were exposed to varying concentrations of the nanocomposites. Cell viability assays revealed a concentration-dependent reduction in cell viability, indicating the potential anticancer activity of Han: Eu3+. The findings of this study contribute to the expanding field of nanomedicine, bringing targeted breast cancer treatments and us closer to more effective.

Do rainfed production systems have lower environmental impact over irrigated production systems?: On -farm mitigation strategies.

The intensive agriculture practices improved the crop productivity but escalated energy inputs (EI) and carbon foot print (CF) which contributes to global warming. Hence designing productive, profitable crop management practices under different production systems with low environmental impact (EI and CF) is the need of the hour. To identify the practices, quantification of baseline emissions and the major sources of emissions are required. Indian agriculture has diversified crops and production systems but there is dearth of information on both EI and CF of these production systems and crops. Hence the present study was an attempt to find hot spots and identify suitable strategies with high productivity, energy use efficiency (EUE) and carbon use efficiency (CUE). Energy and carbon balance of castor, cotton, chickpea, groundnut, maize, rice (both rainfed and irrigated), wheat, sugarcane (only irrigated), pigeon pea, soybean, sorghum, pearl millet (only rainfed) in different production systems was assessed. Field specific data on different crop management practices as well as grain and biomass yields were considered. Rainfed production systems had lower EI and CF than irrigated system. The nonrenewable sources of energy like fertilizer (64 %), irrigation (78 %), diesel fuel (75 %) and electricity (67 %) are the major source of energy input. Rainfed crops recorded higher CUE over irrigated condition. Adoption of technologies like efficient irrigation strategies (micro irrigation), enhancing fertilizer use efficiency (site specific nutrient management or slow release fertilizer), conservation agriculture (conservation or reduced tillage) rice cultivation methods (SRI or Direct seeded rice) were the mitigation strategies. These results will help policy makers and stake holders in adoption of suitable strategies for sustainable intensification.

Interdisciplinary treatment of an adolescent with unilateral cleft lip and palate.

AIM: The present case report describes the importance of interdisciplinary approach and gives an understanding on management of an adolescent with unilateral cleft lip and palate. BACKGROUND: Failure of fusion between medial nasal process and maxillary process or between the palatal process leads to the formation of clefts. Clefts are result of genetic or environmental factors or a combination of both. Common dental problems associated with clefts includes anterior and posterior crossbites, hypodontia, malformation and abnormal eruption pattern. CASE REPORT: A girl, aged 15 years reported with a chief complaint of unesthetic appearance of her maxillary anterior teeth. She had unilateral cleft lip and palate and had received cheiloplasty and palatoplasty when she was in young age and rhinoplasty when she was 14 years of age. At pretreatment evaluation, she had concave profile with maxillary arch constriction and oroantral fistula and mesially tipped maxillary left canine. CONCLUSION: This patient's treatment was unconventional, but it was successful in significantly improving her masticatory function and smile, along with favorable dental and facial results. Generalized esthetics and function were significantly improved in this patient without orthognathic surgery, and treatment results were stable 3 years after the appliance removal. Clinical considerations, sequencing of treatment phases as shown in this case report can be utilized while treating an adolescent with cleft lip and palate. CLINICAL SIGNIFICANCE: If the skeletal discrepancy is mild and esthetic concerns are minimal, dental compensation by orthodontic treatment alone might be recommended. The cephalometric analysis and prediction tracings provide further information for deciding whether a patient can be treated by orthodontics alone, or by orthodontics and an orthognathic surgical procedure. A change in axial inclination of the teeth can camouflage the skeletal relationship adequately. However, one should be cautious in a growing patient, because he or she might outgrow the dental correction so that ultimately skeletal surgery would be indicated.

Energy decomposition and waterswapping analysis to investigate the SNP associated DPD mediated 5-FU resistance.

5-fluorouracil is an essential component of systemic chemotherapy for colon, breast, head, and neck cancer patients. However, tumoral overexpression of the dihydropyrimidine dehydrogenase has rendered 5-FU clinically ineffective by inactivating it to 5'-6'-dihydro fluorouracil. The responses to 5-FU in terms of efficacy and toxicity greatly differ depending upon the population group, because of variability in the DPD activity levels. In the current study, key active site amino acids involved in the 5-FU inactivation were investigated by modelling the 3D structure of human DPD in a complex with 5-FU. The identified amino acids were analyzed for their possible missense mutations available in dbSNP database. Out of 12 missense SNPs, four were validated either by sequencing in the 1000 Genomes project or frequency/genotype data. The recorded validated missense SNPs were further considered to analyze the effect of their respective alterations on 5-FU binding. Overall findings suggested that population bearing the Glu611Val DPD mutation (rs762523739) is highly vulnerable to 5-FU resistance. From the docking, electrostatic complementarity, dynamics, and energy decomposition analyses it was found that the above mutation showed superior scores than the wild DPD -5FU complex. Therefore, prescribing prodrug NUC-3373 or DPD inhibitors (Gimeracil/3-Cyano-2,6-Dihydroxypyridines) as adjuvant therapy may overcome the 5-FU resistance.

Network pharmacology based anti-diabetic attributes of bioactive compounds from Ocimum gratissimum L. through computational approach.

The present research was framed to determine the key compounds present in the plant Ocimum gratissimum L. targeting protein molecules of Diabetes Mellitus (DM) by employing In-silico approaches. Phytochemicals previously reported to be present in this herb were collated through literature survey and public phytochemical databases, and their probable targets were anticipated using BindingDB (p ≥ 0.7). STRING and KEGG pathway databases were employed for pathway enrichment analysis. Homology modelling was executed to elucidate the structures of therapeutic targets. Further, Phytocompounds from O. gratissimum were subjected for docking with four therapeutic targets of DM by using AutoDock vina through POAP pipeline implementation. 30 compounds were predicted to target 136 protein molecules including aldose reductase, DPP4, alpha-amylase, and alpha-glucosidase. Neuroactive ligand-receptor interaction, MAPK, PI3K-Akt, starch and insulin resistance were predicted to have potentially modulation by phytocompounds. Based on the phytocompound's binding score with the four targets of DM, Rutin scored the lowest binding energy (-11 kcal/mol) with Aldose reductase by forming 17 intermolecular interactions. In conclusion, based on the network and binding score, phytocompounds from O. gratissimum have a synergistic and considerable effect in the management of DM via multi-compound, multi-target, and multi-pathway mechanisms.

Soil bacterial community structure and functioning in a long-term conservation agriculture experiment under semi-arid rainfed production system.

Soil microbial communities are important drivers of biogeochemical cycling of nutrients, organic matter decomposition, soil organic carbon, and Greenhouse gas emissions (GHGs: CO2, N2O, and CH4) and are influenced by crop and soil management practices. The knowledge on the impact of conservation agriculture (CA) on soil bacterial diversity, nutrient availability, and GHG emissions in semi-arid regions under rainfed conditions is vital to develop sustainable agricultural practices, but such information has not been systemically documented. Hence, studies were conducted for 10 years in rainfed pigeonpea (Cajanus cajan L.)-castor bean (Ricinus communis L.) cropping system under semi-arid conditions to assess the effects of tillage and crop residue levels on the soil bacterial diversity, enzyme activity (Dehydrogenase, urease, acid phosphatase, and alkaline phosphatase), GHG emissions, and soil available nutrients (Nitrogen, phosphorus, and potassium). Sequencing of soil DNA through Illumina HiSeq-based 16S rRNA amplicon sequencing technology has revealed that bacterial community responded to both tillage and residue levels. The relative abundance of Actinobacteria in terms of Operational Taxonomic Unit (OTUs) at phyla, class as well as genera level was higher in CA (NTR1: No Tillage + 10 cm anchored residue and NTR2 NT + 30 cm anchored residue) over CT (conventional tillage without crop residues). CA resulted in higher enzyme activities (dehydrogenase, urease, acid phosphatase, and alkaline phosphatase) and reduction in GHG emissions over CT. CA recorded 34% higher and 3% lower OC, as compared to CT, and CTR1, respectively. CA recorded 10, 34, and 26% higher available nitrogen, phosphorus, and potassium over CT and CTR1, respectively. NTR1 recorded 25 and 38% lower N2O emissions as compared to CTR1 and CTR2, respectively. Whereas only NT recorded 12% higher N2O emissions as compared to CT. Overall, the results of the study indicate that CA improves the relative abundance of soil bacterial communities, nutrient availability, and enzyme activities, and may help to contribute to the mitigation of climate change, and sustainability in rainfed areas.

Pest scenario of Helicoverpa armigera (Hub.) on pigeonpea during future climate change periods under RCP based projections in India.

Gram pod borer, Helicoverpa armigera (Hub.) is the major insect pest of pigeonpea and prediction of number of generations (no. of gen.) and generation time (gen. time) using growing degree days (GDD) approach during three future climate change periods viz., Near (NP), Distant (DP) and Far Distant (FDP) periods at eleven major pigeonpea growing locations of India was attempted. Multi-model ensemble of Maximum (Tmax) and Minimum (Tmin) temperature data of four Representative Concentration Pathways viz., RCP 2.6, 4.5, 6.0 and 8.5 of Coupled Model Inter comparison Project 5 (CMIP5) models was adopted here. The increase in projected Tmax and Tmin are significant during 3 climate change periods (CCPs) viz., the NP, DP and FDP over base line (BL) period under four RCP scenarios at all locations and would be higher (4.7-5.1 °C) in RCP 8.5 and in FDP. More number of annual (10-17) and seasonal (5-8) gens. are expected to occur with greater percent increase in FDP (8 to 38%) over base line followed by DP (7 to 22%) and NP (5to 10%) periods with shortened annual gen. time (4 to 27%) across 4 RCPs. The reduction of crop duration was substantial in short, medium and long duration pigeonpeas at all locations across 4 RCPs and 3 CCPs. The seasonal no.of gen. is expected to increase (5 to 35%) with shortened gen. time (4 to 26%) even with reduced crop duration across DP and FDP climate periods of 6.0 and 8.5 RCPs in LD pigeonpea. More no. of gen. of H. armigera with reduced gen. time are expected to occur at Ludhiana, Coimbatore, Mohanpur, Warangal and Akola locations over BL period in 4 RCPs when normal duration of pigeonpeas is considered. Geographical location (66 to 72%), climate period (11 to 19%), RCPs (5-7%) and their interaction (0.04-1%) is vital and together explained more than 90% of the total variation in future pest scenario. The findings indicate that the incidence of H. armigera would be higher on pigeonpea during ensuing CCPs in India under global warming context.

In vivo metabolic investigation of moxifloxacin using liquid chromatography/electrospray ionization tandem mass spectrometry in combination with online hydrogen/deuterium exchange experiments.

RATIONALE: Tuberculosis is a leading cause of death from an infectious disease and moxifloxacin is an effective drug as compared to other fluoroquinolones. To date only two metabolites of the drug are known. Therefore, the present study on characterization of hitherto unknown in vivo metabolites of moxifloxacin using liquid chromatography/electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS) is undertaken. METHODS: In vivo metabolites of moxifloxacin have been identified and characterized by using LC/ESI-MS/MS in combination with an online hydrogen/deuterium (H/D) exchange technique. To identify in vivo metabolites, blood, urine and faeces samples were collected after oral administration of moxifloxacin to Sprague-Dawley rats. The samples were prepared using an optimized sample preparation approach involving protein precipitation, liquid-liquid extraction followed by solid-phase extraction and LC/MS/MS analysis. RESULTS: A total of nine phase I and ten phase II metabolites of moxifloxacin have been identified in urine samples including N-sulphated, glucuronide and hydroxylated metabolites which are also observed in plasma samples. In faeces samples, only the N-sulphated metabolite is observed. The structures of metabolites have been elucidated based on fragmentation patterns, accurate mass measurements and online H/D exchange LC/MS/MS experiments. Online H/D exchange experiments are used to support the identification and structural characterization of drug metabolites. CONCLUSIONS: A total of 19 in vivo metabolites of moxifloxacin have been characterized using LC/ESI-MS/MS in combination with accurate mass measurements and online H/D exchange experiments. The main phase I metabolites of moxifloxacin are hydroxylated, decarbonylated, desmethylated and desmethylhydroxylated metabolites which undergo subsequent phase II glucuronidation pathways.

Identification and characterization of stressed degradation products of metoprolol using LC/Q-TOF-ESI-MS/MS and MS(n) experiments.

A rapid, specific and reliable isocratic high-performance liquid chromatography combined with quadrupole time-of-flight electrospray ionization tandem mass spectrometry (LC/Q-TOF-ESI-MS/MS) method has been developed and validated for the identification and characterization of stressed degradation products of metoprolol. Metoprolol, an anti-hypertensive drug, was subjected to hydrolysis (acidic, alkaline and neutral), oxidation, photolysis and thermal stress, as per ICH-specified conditions. The drug showed extensive degradation under oxidative and hydrolysis (acid and base) stress conditions. However, it was stable to thermal, neutral and photolysis stress conditions. A total of 14 degradation products were observed and the chromatographic separation of the drug and its degradation products was achieved on a C(18) column (4.6 × 250 mm, 5 µm). To characterize degradation products, initially the mass spectral fragmentation pathway of the drug was established with the help of MS/MS, MS(n) and accurate mass measurements. Similarly, fragmentation pattern and accurate masses of the degradation products were established by subjecting them to LC-MS/QTOF analysis. Structure elucidation of degradation products was achieved by comparing their fragmentation pattern with that of the drug. The degradation products DP(2) (m/z 153) and DP(14) (m/z 236) were matched with impurity B, listed in European Pharmacopoeia and British Pharmacopoeia, and impurity I, respectively. The LC-MS method was validated with respect to specificity, linearity, accuracy and precision.