Evaluation of relationship between microbial load and drug efficacy of Andrographis paniculata during storage

Three different extracts of Andrographis paniculata obtained by using three different solvents i.e. acetone, ethanol and water, were used to find out correlation of antimicrobial potency of the drug among them and with storage period of six months. Antibacterial activities were assessed by well diffusion method against Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Staphylococcus aureus, Bacillus subtilis, and Salmonella typhi and antifungal activity by food poisoning technique against Candida albicans. No definite pattern of antimicrobial nature in acetone, ethanol and aqueous extract could be observed. Acetone extract showed maximum inhibitory (18.3mm) effect among all extract in general. Ethanol extract could attain second position and aqueous extract failed to inhibit growth of any organism even at 100% concentration. A declined trend of inhibitory effect of extract with increased number of storage days has been found showing a negative relation between inhibitory effect of the drug and storage duration. But positive correlation between inhibitory effect and concentration has been recorded. No inhibition was recorded against E. coli by any of the extract Bacterial load in term of CFU/g was found tremendously enhanced with increase of storage period. Negative correlation between microbial load and drug efficacy had been established while positive correlation between microbial load and storage period had been recorded

FORMULATION OF CURCUMINOID LOADED SOLID LIPID NANOPARTICLES IN ORDER TO IMPROVE ORAL BIOAVAILABILITY

Objective: Solid lipid nanoparticles (SLNs) of Curcuminoids were formulated and characterized in order to improve poor oral bioavailability of Curcumin. In vivo pharmacokinetics study in rats was conducted to demonstrate improved oral bioavailability.Methods: High pressure homogenization followed by ultrasonication method was adopted to formulate solid lipid nanoparticles of Curcumin. Compritol 888 ATO and Precirol ATO 5 were explored as solid lipids with LIPOID S 75 being used as surfactant. Freeze dried solid lipid nanoparticles were compared with marketed formulation of Curcumin (Adcumin®) in rat plasma using High Pressure Liquid Chromatography (HPLC) method using ultraviolet (UV) detector.Results: Particle size measurements performed on Solid lipid nanoparticles of Curcumin revealed the mean particle size of 200-300 nm for optimized formulations and entrapment efficiency of close to 80%. Sucrose and Dextrose were suitable cryoprotectants to prepare freeze dried solid lipid nanoparticles. Curcumin loaded solid lipid nanoparticles exhibited sustained release pattern during in vitro release kinetics.Conclusion: In vivo pharmacokinetics study in Swiss albino rats revealed that encapsulation of Curcumin into solid lipid nanoparticles increased oral bioavailability of Curcumin to 12 folds when compared with marketed formulation of Raw Curcumin (Adcumin®).Â

Giant Dipole Resonance Width in near-Sn Nuclei at Low Temperature and High Angular Momentum

High energy gamma-rays in coincidence with low energy yrast gamma-rays have been measured from 113Sb, at excitation energies of 109 and 122 MeV, formed by bombarding 20Ne on 93Nb at projectile energies of 145 and 160 MeV respectively to study the role of angular momentum (J) and temperature (T) over Giant Dipole Resonance (GDR) width. The maximum populated angular momenta for fusion were 67hbar and 73hbar respectively for the above-mentioned beam energies. The high energy photons were detected using a Large Area Modular BaF2 Detector Array (LAMBDA) along with a 24-element multiplicity filter. After pre-equilibrium corrections, the excitation energy E* was averaged over the decay steps of the compound nucleus (CN). The average values of temperature, angular momentum, CN mass etc. have been calculated by the statistical model code CASCADE. Using those average values, results show the systematic increase of GDR width with T which is consistent with Kusnezov parametrization and the Thermal Shape Fluctuation Model. The rise of GDR width with temperature also supports the assumptions of adiabatic coupling in the Thermal Shape Fluctuation Model. But the GDR widths and corresponding reduced plots with J are not consistent with the theoretical model at high spins.Comment: 19 pages, 10 figures, Submitted to Physics Review

Determination of lethal dose (LD50) and sensitivity of fenugreek (Trigonella foenum-graecum) to sodium azide for induction of mutation

The present experiment was conducted in the year 2021 at Sri Karan Narendra Agriculture University, Jobner, Rajasthan, to determine the optimum dose (LD50) and duration of the chemical mutagen treatment for the induction of desirable mutation. A set of 100 pre-soaked fenugreek seeds were treated with 12 different concentrations of sodium azide, viz. 0.3 mM, 0.6 mM, 1 mM, 2 mM, 3 mM, 4 mM, 5 mM, 6 mM, 7 mM, 8 mM, 9 mM and 10 mM for three different durations, viz. 3 h, 6 h and 9 h. Results showed that a dose-dependent decreasing tendency was observed in germination percentage, survival percentage, root length and shoot length with increasing concentration and duration of sodium azide treatment. Almost all the mutagenic treatments resulted in decrease in germination percentage, survival percentage and seedling height (root and shoot length) with increasing concentrations and duration of mutagen in laboratory conditions. Also, the LD50 value was observed as an 8 mM sodium azide concentration for 6 h in fenugreek. The mutagen treatments given at 9 h duration were detrimental for fenugreek. They cannot be used for mutation induction as they are utterly lethal after a 3 mM sodium azide concentration. So, lower treatments of mutagens have influenced less biological damage and would be suitable for inducing desirable mutations

Persistence in a Stationary Time-series

We study the persistence in a class of continuous stochastic processes that are stationary only under integer shifts of time. We show that under certain conditions, the persistence of such a continuous process reduces to the persistence of a corresponding discrete sequence obtained from the measurement of the process only at integer times. We then construct a specific sequence for which the persistence can be computed even though the sequence is non-Markovian. We show that this may be considered as a limiting case of persistence in the diffusion process on a hierarchical lattice.Comment: 8 pages revte

Biodegradable microparticulate drug delivery system of diltiazem HCl

The efficacy of a drug in a specific application requires the maintenance of appropriate drug blood level concentration during a prolonged period of time. Controlled release delivery is available for many routes of administration and offers many advantages (as microparticles and nanoparticles) over immediate release delivery. These advantages include reduced dosing frequency, better therapeutic control, fewer side effects, and, consequently, these dosage forms are well accepted by patients. Advances in polymer material science, particle engineering design, manufacture, and nanotechnology have led the way to the introduction of several marketed controlled release products and several more are in pre-clinical and clinical development. The objective of this work is to prepare and evaluate diltiazem HCl loaded albumin microparticles using a factorial design. Albumin (natural polymer) microparticles were prepared by emulsion heat-stabilization method. Selected formulations were characterized for their entrapment efficiency, particle size, surface morphology, and release behavior. Analysis of variance for entrapment efficiency indicates that entrapment efficiency is best fitted to a response surface linear model. Surface morphology was studied by scanning electron microscopy. Scanning electron microscopy of the microparticles revealed a spherical, nonporous and uniform appearance, with a smooth surface. The geometric mean diameter of the microparticles was found to be 2-9 µm, which more than 75% were below 3.5 µm and drug incorporation efficiency of 59.74 to 72.48% (w/w). In vitro release profile for formulations containing diltiazem HCl loaded BSA microparticles with heat stabilization technique shows slow controlled the release of the drug up to 24 hours. The release pattern was biphasic, characterized by an initial burst effect followed by a slow release. All selected microparticles exhibited a prolonged release for almost 24 hours. On comparing regression-coefficient (r²) values for Hixson Crowel, Higuchi and Peppas kinetic models, different batches of microparticles showed Fickian, non-Fickian, and diffusion kinetics. The release mechanism was regulated by D:P ratio. From the statistical analysis it was observed that as the drug:polymer (D:P) ratio increased, there was a significant increase in the encapsulation efficiency. Based on the particle size, entrapment efficiency and physical appearance, DTM-3 formulations were selected for in vivo release study and stability study. The in vivo result of drug loaded microparticles showed preferential drug targeting to liver followed by lungs, kidneys and spleen. Stability studies showed that maximum drug content and closest in vitro release to initial data were found in the formulation stored at 4 ºC. In present study, diltiazem HCl loaded BSA microparticles were prepared and targeted to various organs to satisfactory level and were found to be stable at 4 ºC.A eficácia terapêutica de um fármaco depende da manutenção de seu nível plasmático adequado em determinado intervalo de tempo. Nesse sentido, a liberação modificada de fármacos está disponível em muitas vias de administração e oferece muitas vantagens (como micropartículas e nanopartículas) quando comparada às formulações de liberação imediata. Essas vantagens incluem reduzida frequência da dosagem, melhor controle terapêutico e menos efeitos colaterais. Assim sendo, esses produtos apresentam maior aceitação pelos pacientes. Os avanços na ciência dos materiais, na engenharia das partículas, em manufatura e em nanotecnologia permitiram a introdução no mercado de vários produtos de liberação modificada e vários outros se encontram em desenvolvimento pré-clínico e clínico. O objetivo do presente trabalho foi preparar e avaliar o fármaco cloridrato de diltiazem associado a micropartículas de albumina utilizando planejamento fatorial. As micropartículas de albumina, um polímero natural, foram preparadas por método de emulsão empregando estabilização por calor. As formulações selecionadas foram caracterizadas no que se refere à sua eficiência de encapsulamento, tamanho médio de partículas, morfologia de superfície e perfil de liberação do fármaco. A análise de variância relativa à eficiência de encapsulamento indicou superfície de resposta linear. Com referência à morfologia superficial, essa foi avaliada empregando microscopia eletrônica de varredura. Essa análise revelou micropartículas esféricas, não porosas e de aparência uniforme, com superfície lisa. O diâmetro médio das micropartículas foi entre 2 e 9 µm, sendo que mais de 75% das micropartículas se apresentaram abaixo de 3,5 µm. Além disso, a eficiência de encapsulamento foi entre 59,74 e 72,48%. Quanto ao ensaio para avaliação do perfil de liberação in vitro do fármaco associado às micropartículas, as formulações apresentaram liberação lenta até 24 horas. O comportamento foi caracterizado por liberação inicial (efeito burst) seguida por liberação lenta. Todas as fórmulas selecionadas apresentaram liberação prolongada por aproximadamente 24 horas. Na comparação entre os valores de coeficientes de regressão (R²), os modelos propostos por Hixson Crowel, Higuchi e Peppas, para diferentes formulações de micropartículas, demonstraram cinética de liberação de acordo com modelo Fickiano e não-Fickiano. O mecanismo de liberação do fármaco foi regulado pela razão entre o fármaco e o polímero. A análise estatística revelou significativo aumento da eficiência de encapsulamento quando essa razão aumentou. As avaliações relativas à análise dimensional das micropartículas, à eficiência de encapsulamento do fármaco e à morfologia permitiram a seleção da formulação DTM-3 para os ensaios de liberação in vivo e para o estudo da estabilidade. O ensaio de liberação in vivo do fármaco associado às micropartículas demonstrou sítio-alvo preferencial no fígado, seguido pelos pulmões rins e baço. No presente estudo, as micropartículas de albumina contendo cloridrato de diltiazem foram adequadamente preparadas e orientadas satisfatoriamente para vários órgãos. Além disso, a formulação selecionada apresentou estabilidade físico-química a 4 ºC

Physics Potential of the ICAL detector at the India-based Neutrino Observatory (INO)

The upcoming 50 kt magnetized iron calorimeter (ICAL) detector at the India-based Neutrino Observatory (INO) is designed to study the atmospheric neutrinos and antineutrinos separately over a wide range of energies and path lengths. The primary focus of this experiment is to explore the Earth matter effects by observing the energy and zenith angle dependence of the atmospheric neutrinos in the multi-GeV range. This study will be crucial to address some of the outstanding issues in neutrino oscillation physics, including the fundamental issue of neutrino mass hierarchy. In this document, we present the physics potential of the detector as obtained from realistic detector simulations. We describe the simulation framework, the neutrino interactions in the detector, and the expected response of the detector to particles traversing it. The ICAL detector can determine the energy and direction of the muons to a high precision, and in addition, its sensitivity to multi-GeV hadrons increases its physics reach substantially. Its charge identification capability, and hence its ability to distinguish neutrinos from antineutrinos, makes it an efficient detector for determining the neutrino mass hierarchy. In this report, we outline the analyses carried out for the determination of neutrino mass hierarchy and precision measurements of atmospheric neutrino mixing parameters at ICAL, and give the expected physics reach of the detector with 10 years of runtime. We also explore the potential of ICAL for probing new physics scenarios like CPT violation and the presence of magnetic monopoles.Comment: 139 pages, Physics White Paper of the ICAL (INO) Collaboration, Contents identical with the version published in Pramana - J. Physic

Genome-Wide Distribution and Organization of Microsatellites in Plants: An Insight into Marker Development in Brachypodium

Plant genomes are complex and contain large amounts of repetitive DNA including microsatellites that are distributed across entire genomes. Whole genome sequences of several monocot and dicot plants that are available in the public domain provide an opportunity to study the origin, distribution and evolution of microsatellites, and also facilitate the development of new molecular markers. In the present investigation, a genome-wide analysis of microsatellite distribution in monocots (Brachypodium, sorghum and rice) and dicots (Arabidopsis, Medicago and Populus) was performed. A total of 797,863 simple sequence repeats (SSRs) were identified in the whole genome sequences of six plant species. Characterization of these SSRs revealed that mono-nucleotide repeats were the most abundant repeats, and that the frequency of repeats decreased with increase in motif length both in monocots and dicots. However, the frequency of SSRs was higher in dicots than in monocots both for nuclear and chloroplast genomes. Interestingly, GC-rich repeats were the dominant repeats only in monocots, with the majority of them being present in the coding region. These coding GC-rich repeats were found to be involved in different biological processes, predominantly binding activities. In addition, a set of 22,879 SSR markers that were validated by e-PCR were developed and mapped on different chromosomes in Brachypodium for the first time, with a frequency of 101 SSR markers per Mb. Experimental validation of 55 markers showed successful amplification of 80% SSR markers in 16 Brachypodium accessions. An online database ‘BraMi’ (Brachypodium microsatellite markers) of these genome-wide SSR markers was developed and made available in the public domain. The observed differential patterns of SSR marker distribution would be useful for studying microsatellite evolution in a monocot–dicot system. SSR markers developed in this study would be helpful for genomic studies in Brachypodium and related grass species, especially for the map based cloning of the candidate gene(s)