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81.
Pratap S. Jadon Virendra Gajbhiye Rajesh S. Jadon Kavita R. Gajbhiye Narayanan Ganesh 《AAPS PharmSciTech》2009,10(4):1186-1192
The aim of the present report was to develop nonionic surfactant vesicles (niosomes) to improve poor and variable oral bioavailability
of griseofulvin. Niosomes were prepared by using different nonionic surfactants span 20, span 40, and span 60. The lipid mixture
consisted of surfactant, cholesterol, and dicetyl phosphate in the molar ratio of 125:25:1.5, 100:50:1.5, and 75:75:1.5, respectively.
The niosomal formulations were prepared by thin film method and ether injection method. The influence of different formulation
variables such as surfactant type, surfactant concentration, and cholesterol concentration was optimized for size distribution
and entrapment efficiency for both methods. Result indicated that the niosomes prepared by thin film method with span 60 provided
higher entrapment efficiency. The niosomal formulation exhibited significantly retarded in vitro release as compared with free drug. The in vivo study revealed that the niosomal dispersion significantly improved the oral bioavailability of griseofulvin in albino rats
after a single oral dose. The maximum concentration (C
max) achieved in case of niosomal formulation was approximately double (2.98 μg/ml) as compared to free drug (1.54 μg/ml). Plasma
drug profile also suggested that the developed niosomal system also has the potential of maintaining therapeutic level of
griseofulvin for a longer period of time as compared to free griseofulvin. The niosomal formulation showed significant increase
in area under the curve0-24 (AUC; 41.56 μg/ml h) as compared to free griseofulvin (22.36 μg/ml h) reflecting sustained release characteristics. In conclusion,
the niosomal formulation could be one of the promising delivery system for griseofulvin with improved oral bioavailability
and prolonged drug release profiles. 相似文献
82.
Kaposi's sarcoma-associated herpesvirus LANA-1 interacts with the short variant of BRD4 and releases cells from a BRD4- and BRD2/RING3-induced G1 cell cycle arrest 下载免费PDF全文
Ottinger M Christalla T Nathan K Brinkmann MM Viejo-Borbolla A Schulz TF 《Journal of virology》2006,80(21):10772-10786
The Kaposi's sarcoma-associated herpesvirus (KSHV) latency-associated nuclear antigen 1 (LANA-1) is required for the replication of episomal viral genomes. Regions in its N-terminal and C-terminal domains mediate the interaction with host cell chromatin. Several cellular nuclear proteins, e.g., BRD2/RING3, histones H2A and H2B, MeCP2, DEK, and HP1alpha, have been suggested to mediate this interaction. In this work, we identify the double-bromodomain proteins BRD4 and BRD3/ORFX as additional LANA-1 interaction partners. The carboxy-terminal region of the short variant of BRD4 (BRD4S) containing the highly conserved extraterminal domain directly interacts with an element in the LANA-1 carboxy-terminal domain. We show that ectopically expressed BRD4S and BRD2/RING3 delay progression into the S phase of the cell cycle in epithelial and B-cell lines and increase cyclin E promoter activity. LANA-1 partly releases epithelial and B cells from a BRD4S- and BRD2/RING3-induced G1 cell cycle arrest and also promotes S-phase entry in the presence of BRD4S and BRD2/RING3. This is accompanied by a reduction in BRD4S-mediated cyclin E promoter activity. Our data are in keeping with the notion that the direct interaction of KSHV LANA-1 with BRD4 and other BRD proteins could play a role in the G1/S phase-promoting functions of KSHV LANA-1. Further, our data support a model in which the LANA-1 C terminus contributes to a functional attachment to acetylated histones H3 and H4 via BRD4 and BRD2, in addition to the recently demonstrated direct interaction (A. J. Barbera, J. V. Chodaparambil, B. Kelley-Clarke, V. Joukov, J. C. Walter, K. Luger, and K. M. Kaye, Science 311:856-861, 2006) of the LANA-1 N terminus with histones H2A and H2B. 相似文献
83.
Talbot HK Rock MT Johnson C Tussey L Kavita U Shanker A Shaw AR Taylor DN 《PloS one》2010,5(12):e14442
Background
Currently controversy exists about the immunogenicity of seasonal trivalent influenza vaccine in certain populations, especially the elderly. STF2.4×M2e (VAX102) is a recombinant fusion protein that links four copies of the ectodomain of influenza virus matrix protein 2 (M2e) antigen to Salmonella typhimurium flagellin, a TLR5 ligand. The objectives of this study were to assess the feasibility of giving VAX102 and TIV in combination in an effort to achieve greater immunogenicity and to provide cross-protection.Methodology/Principal Findings
Eighty healthy subjects, 18-49 years old, were enrolled in May and June 2009 in a double-blind, randomized, controlled trial at two clinical sites. Subjects were randomized to receive either TIV + VAX102 or TIV + placebo. Both arms tolerated the vaccines. Pain at the injection site was more severe with TIV + VAX102. Two weeks after immunization the HAI responses to the H1 and H3 antigens of TIV were higher in those that received TIV + VAX102 than in TIV + placebo (309 vs 200 and 269 vs 185, respectively), although statistically non-significant. There was no difference in the HAI of the B antigen. In the TIV + VAX102 arm, the geometric mean M2e antibody concentration was 0.5 µg/ml and 73% seroconverted.Conclusions/Significance
The combination of TIV + VAX102 has the potential to increase the immune response to the influenza A components of TIV and to provide M2e immunity which may protect against influenza A strains not contained in seasonal TIV.Trial Registration
ClinicalTrials.gov NCT00921973相似文献84.
Ranjeet R. Kumar Suneha Goswami Mohammad Shamim Kavita Dubey Khushboo Singh Shweta Singh Yugal K. Kala Ravi R.K. Niraj Akshay Sakhrey Gyanendra P. Singh Monendra Grover Bhupinder Singh Gyanendra K. Rai Anil K. Rai Viswanathan Chinnusamy Shelly Praveen 《Functional & integrative genomics》2017,17(6):621-640
85.
Recent experimental and theoretical studies have shown that small asexual populations evolving on complex fitness landscapes may achieve a higher fitness than large ones due to the increased heterogeneity of adaptive trajectories. Here, we introduce a class of haploid three-locus fitness landscapes that allow the investigation of this scenario in a precise and quantitative way. Our main result derived analytically shows how the probability of choosing the path of the largest initial fitness increase grows with the population size. This makes large populations more likely to get trapped at local fitness peaks and implies an advantage of small populations at intermediate time scales. The range of population sizes where this effect is operative coincides with the onset of clonal interference. Additional studies using ensembles of random fitness landscapes show that the results achieved for a particular choice of three-locus landscape parameters are robust and also persist as the number of loci increases. Our study indicates that an advantage for small populations is likely whenever the fitness landscape contains local maxima. The advantage appears at intermediate time scales, which are long enough for trapping at local fitness maxima to have occurred but too short for peak escape by the creation of multiple mutants. 相似文献
86.
Expression of key antioxidant enzymes under combined effect of heat and cadmium toxicity in growing rice seedlings 总被引:2,自引:0,他引:2
Effect of Cd2+ toxicity and heat stress in sensitive rice cv. DR-92 and tolerant rice cv. Bh-1 grown in North East region of India were studied in sand cultures. Increasing levels of 0–500 μM Cd2+ alone and/or heat stress showed increased activities of superoxide dismutase, guaiacol peroxidase, ascorbate peroxidase and
glutathione reductase enzymes which were associated with induced oxidative stress and altered enzyme activities. The values
for SOD and POD activities were always more in cv. DR-92 whereas CAT and GR activities were higher in cv. Bh-1 in roots and shoots under Cd2+ or heat stress alone in sensitive cv. DR-92. Upon imposition of a combination of Cd2+ + heat the activities of SOD and POD decreased significantly in root/shoot of both the sensitive and tolerant rice varieties.
A nine fold increase in GR activity under combination of heat + 100 μM Cd2+ stress in shoots of cv. Bh-1 at day 15 was noted when compared to controls. The dual stress combination of Cd2+ + heat did not alter catalase activity in vivo in both the rice varieties. Results suggest a time-specific and varietal distribution
of the antioxidant enzymes in rice plants subjected to Cd2+ and/or heat stress. Tolerant cv. Bh-1 has better survival to combined stressors like Cd2+ and heat than sensitive rice cv. DR-92 and heat stress when given in combination with Cd2+ toxicity seem to mitigate the effect of Cd2+ stress alone in rice. The study indicates individual Cd2+ toxicity and heat stress and a combination of the two stresses to have separate implications on antioxidative defense mechanism
in rice plants. Among enzymes of the defense apparatus ascorbate peroxidase and glutathione reductase appear to serve as an
important component for better survival of rice plants under combination of Cd2+ + heat stress. 相似文献
87.
Kavita Yadav Chanchal Kumar G. Archana G. Naresh Kumar 《Applied microbiology and biotechnology》2014,98(19):8327-8336
Mineral phosphate solubilization by bacteria is mediated through secretion of organic acids, among which citrate is one of the most effective. To overproduce citrate in bacterial systems, an artificial citrate operon comprising of genes encoding NADH-insensitive citrate synthase of E. coli and Salmonella typhimurium sodium-dependent citrate transporter was constructed. In order to improve its mineral phosphate solubilizing (MPS) ability, the citrate operon was incorporated into E. hormaechei DHRSS. The artificial citrate operon transformant secreted 7.2 mM citric acid whereas in the native strain, it was undetectable. The transformant released 0.82 mM phosphate in flask studies in buffered medium containing rock phosphate as sole P source. In fermenter studies, similar phenotype was observed under aerobic conditions. However, under microaerobic conditions, no citrate was detected and P release was not observed. Therefore, an artificial citrate gene cluster containing Vitreoscilla hemoglobin (vgb) gene under its native promoter, along with artificial citrate operon under constitutive tac promoter, was constructed and transformed into E. hormaechei DHRSS. This transformant secreted 9 mM citric acid under microaerobic conditions and released 1.0 mM P. Thus, incorporation of citrate operon along with vgb gene improves MPS ability of E. hormaechei DHRSS under buffered, microaerobic conditions mimicking rhizospheric environment. 相似文献
88.
Kavita Venkataraman ChinMeng Khoo Hwee Lin Wee Chuen Seng Tan Stefan Ma Derrick Heng Jeannette Lee E. Shyong Tai Julian Thumboo 《PloS one》2014,9(11)
Background
Health related quality of life (HRQoL) is an important dimension of individuals'' well-being, and especially in chronic diseases like diabetes and hypertension. The objective of this study was to evaluate the contributions of disease process, comorbidities, medication or awareness of the disease to HRQoL in diabetes mellitus, hypertension and dyslipidemia.Methods
This was a cross-sectional study of 3514 respondents from the general community in Singapore, assessed for HRQoL, disease and comorbid conditions through self-report, clinical and laboratory investigations. HRQoL was assessed using SF-36 health survey version 2. For each condition, participants were categorized as having 1) no disease, 2) undiagnosed, 3) diagnosed, not taking medication, and 4) diagnosed, taking medication. Analysis used one-way ANOVA and multiple linear regression.Results
Diagnosed disease was associated with lower physical health component summary (PCS) scores across all three conditions. After adjustment for comorbidities, this association remained significant only for those not on medication in diabetes (−2.7±1.2 points, p = 0.03) and dyslipidemia (−1.3±0.4 points, p = 0.003). Diagnosed hypertension (no medication −2.6±0.9 points, p = 0.002; medication −1.4±0.5 points, p = 0.004) and dyslipidemia (no medication −0.9±0.4 points, p = 0.03; medication −1.9±0.5 points, p<0.001) were associated with lower mental health component summary (MCS) scores. Undiagnosed disease was associated with higher MCS in diabetes (2.4±1.0 points, p = 0.01) and dyslipidemia (0.8±0.4 points, p = 0.045), and PCS in hypertension (1.2±0.4 points, p = 0.004).Conclusions
Disease awareness was associated with lower HRQoL across the diseases studied, with PCS associations partially mediated by comorbidities. Equally importantly, undiagnosed disease was not associated with HRQoL deficits, which may partly explain why these individuals do not seek medical care. 相似文献89.
Biochemical characteristics of bi-resistant mutants (resistant to ethambutol plus streptomycin or isoniazid plus streptomycin)
of mycobacteria isolated by replica plating fromMycobacterium smegmatis ATCC were compared with those of the drug-susceptible strains. Reduced incorporation of [14C]uracil, [3H]lysine and [14C]acetate into RNA, protein and phospholipids respectively was seen in the resistant mutants. Total phosphorlipids were enhanced
in ethambutol plus streptomycin resistant mutant and decreased in isoniazid plus streptomycin resistant mutant. There were
similar changes in levels of individual phospholipids. The resistant mutants revealed an accumulation of phospholipids in
the cell wall, and a marked decrease of phospholipids in the cell membrane in comparison to the susceptible strain. Several
qualitative alterations in the polypeptide profile (with respect to number and molecular weight) of the crude protein extract
and of different subcellular compartments were seen in the resistant mutants. 相似文献
90.
Analysis of γ-Aminobutyric AcidA Receptor Subunits in the Mouse Cochlea by Means of the Polymerase Chain Reaction 总被引:1,自引:0,他引:1
Dennis G. Drescher Glenn E. Green Khalid M. Khan† Kavita Hajela Kirk W. Beisel Barbara J. Morley Anil K. Gupta 《Journal of neurochemistry》1993,61(3):1167-1170
Abstract: Unlike 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which produces consistent decreases in levels of striatal dopamine (DA) with considerably smaller and more variable effects on mouse brain levels of serotonin (5-HT) and norepinephrine (NE), a novel amine-substituted MPTP analogue, 1-methyl-4-(2'-aminophenyl)-1,2,3,6-tetrahydropyridine (2'-NH2 -MPTP), administered in a standard mouse dosing paradigm for MPTP (20 mg/kg X 4) did not affect striatal DA but led to marked reductions (60–70%) in levels of 5-HT, 5-hydroxyindoleacetic acid (5-HIAA), and NE measured in frontal cortex and hippocampus 1 week after treatment. Another 2'-substituted MPTP analogue, 1-methyl-4-(2'-methylphenyl)-1,2,3,6-tetrahydropyridine, affected cortical and hippocampal 5-HT, 5-HIAA, and NE only minimally, while markedly reducing the DA content in striatum (90%), thus indicating that the substituent (-NH2 versus -CH3 ) at the 2'position is important for the differential effects of these MPTP analogues. In a replication study with a 3-week end point, hippocampal and cortical 5-HT, 5-HIAA, and NE levels remained depressed with no indication of recovery. These results suggest that 2'-NH2 -MPTP may be a novel, regionally selective neurotoxin for serotonergic and norad-renergic nerve terminals. 相似文献