52 research outputs found
STUDIES ON THE PREPARATION, CHARACTERIZATION AND SOLUBILITY OF Β-CYCLODEXTRIN-NELFINAVIR INCLUSION COMPLEXES
Nelfinavir is a poor water-soluble antiretroviral drug with relatively low bioavailability. The effect of β-cyclodextrin on the aqueous solubility and dissolution rate of nelfinavir was investigated. Phase solubility studies indicated that the solubility of nelfinavir was significantly enhanced by complexing it with β- cyclodextrin. It was classified as Bs type indicating the 1:2 stoichiometric inclusion complexes. The various solid complexes prepared by physical mixture, Kneading, coprecipitation & common solvent methods were characterized by DSC, X-RD & FT-IR. Dissolution study showed that the solubility and dissolution rate of nelfinavir was significantly improved by complexation with β-cyclodextrin
Should the Arteriovenous Fistula Be Created before Starting Dialysis?: A Decision Analytic Approach
Background: An arteriovenous fistula (AVF) is considered the vascular access of choice, but uncertainty exists about the\ud
optimal time for its creation in pre-dialysis patients. The aim of this study was to determine the optimal vascular access\ud
referral strategy for stage 4 (glomerular filtration rate ,30 ml/min/1.73 m2) chronic kidney disease patients using a decision\ud
analytic framework.\ud
Methods: A Markov model was created to compare two strategies: refer all stage 4 chronic kidney disease patients for an\ud
AVF versus wait until the patient starts dialysis. Data from published observational studies were used to estimate the\ud
probabilities used in the model. A Markov cohort analysis was used to determine the optimal strategy with life expectancy\ud
and quality adjusted life expectancy as the outcomes. Sensitivity analyses, including a probabilistic sensitivity analysis, were\ud
performed using Monte Carlo simulation.\ud
Results: The wait strategy results in a higher life expectancy (66.6 versus 65.9 months) and quality adjusted life expectancy\ud
(38.9 versus 38.5 quality adjusted life months) than immediate AVF creation. It was robust across all the parameters except\ud
at higher rates of progression and lower rates of ischemic steal syndrome.\ud
Conclusions: Early creation of an AVF, as recommended by most guidelines, may not be the preferred strategy in all predialysis\ud
patients. Further research on cost implications and patient preferences for treatment options needs to be done\ud
before recommending early AVF creation
Development and use of genic molecular markers (GMMs) for construction of a transcript map of chickpea (Cicer arietinum L.)
A transcript map has been constructed by the development and integration of genic molecular markers (GMMs) including single nucleotide polymorphism (SNP), genic microsatellite or simple sequence repeat (SSR) and intron spanning region (ISR)-based markers, on an inter-specific mapping population of chickpea, the third food legume crop of the world and the first food legume crop of India. For SNP discovery through allele re-sequencing, primer pairs were designed for 688 genes/expressed sequence tags (ESTs) of chickpea and 657 genes/ESTs of closely related species of chickpea. High-quality sequence data obtained for 220 candidate genic regions on 2–20 genotypes representing 9 Cicer species provided 1,893 SNPs with an average frequency of 1/35.83 bp and 0.34 PIC (polymorphism information content) value. On an average 2.9 haplotypes were present in 220 candidate genic regions with an average haplotype diversity of 0.6326. SNP2CAPS analysis of 220 sequence alignments, as mentioned above, provided a total of 192 CAPS candidates. Experimental analysis of these 192 CAPS candidates together with 87 CAPS candidates identified earlier through in silico mining of ESTs provided scorable amplification in 173 (62.01%) cases of which predicted assays were validated in 143 (82.66%) cases (CGMM). Alignments of chickpea unigenes with Medicago truncatula genome were used to develop 121 intron spanning region (CISR) markers of which 87 yielded scorable products. In addition, optimization of 77 EST-derived SSR (ICCeM) markers provided 51 scorable markers. Screening of easily assayable 281 markers including 143 CGMMs, 87 CISRs and 51 ICCeMs on 5 parental genotypes of three mapping populations identified 104 polymorphic markers including 90 markers on the inter-specific mapping population. Sixty-two of these GMMs together with 218 earlier published markers (including 64 GMM loci) and 20 other unpublished markers could be integrated into this genetic map. A genetic map developed here, therefore, has a total of 300 loci including 126 GMM loci and spans 766.56 cM, with an average inter-marker distance of 2.55 cM. In summary, this is the first report on the development of large-scale genic markers including development of easily assayable markers and a transcript map of chickpea. These resources should be useful not only for genome analysis and genetics and breeding applications of chickpea, but also for comparative legume genomics
Integrated physical, genetic and genome map of chickpea (Cicer arietinum L.)
Physical map of chickpea was developed for the reference chickpea genotype (ICC 4958) using bacterial artificial chromosome (BAC) libraries targeting 71,094 clones (~12× coverage). High information content fingerprinting (HICF) of these clones gave high-quality fingerprinting data for 67,483 clones, and 1,174 contigs comprising 46,112 clones and 3,256 singletons were defined. In brief, 574 Mb genome size was assembled in 1,174 contigs with an average of 0.49 Mb per contig and 3,256 singletons represent 407 Mb genome. The physical map was linked with two genetic maps with the help of 245 BAC-end sequence (BES)-derived simple sequence repeat (SSR) markers. This allowed locating some of the BACs in the vicinity of some important quantitative trait loci (QTLs) for drought tolerance and reistance to Fusarium wilt and Ascochyta blight. In addition, fingerprinted contig (FPC) assembly was also integrated with the draft genome sequence of chickpea. As a result, ~965 BACs including 163 minimum tilling path (MTP) clones could be mapped on eight pseudo-molecules of chickpea forming 491 hypothetical contigs representing 54,013,992 bp (~54 Mb) of the draft genome. Comprehensive analysis of markers in abiotic and biotic stress tolerance QTL regions led to identification of 654, 306 and 23 genes in drought tolerance “QTL-hotspot” region, Ascochyta blight resistance QTL region and Fusarium wilt resistance QTL region, respectively. Integrated physical, genetic and genome map should provide a foundation for cloning and isolation of QTLs/genes for molecular dissection of traits as well as markers for molecular breeding for chickpea improvement
Advances in genetics and molecular breeding of three legume crops of semi-arid tropics using next-generation sequencing and high-throughput genotyping technologies
Molecular markers are the most powerful genomic tools to increase the efficiency and precision of breeding practices
for crop improvement. Progress in the development of genomic resources in the leading legume crops of the semi-arid
tropics (SAT), namely, chickpea (Cicer arietinum), pigeonpea (Cajanus cajan) and groundnut (Arachis hypogaea), as
compared to other crop species like cereals, has been very slow. With the advances in next-generation sequencing
(NGS) and high-throughput (HTP) genotyping methods, there is a shift in development of genomic resources
including molecular markers in these crops. For instance, 2,000 to 3,000 novel simple sequence repeats (SSR)
markers have been developed each for chickpea, pigeonpea and groundnut. Based on Sanger, 454/FLX and
Illumina transcript reads, transcriptome assemblies have been developed for chickpea (44,845 transcript
assembly contigs, or TACs) and pigeonpea (21,434 TACs). Illumina sequencing of some parental genotypes
of mapping populations has resulted in the development of 120 million reads for chickpea and 128.9 million
reads for pigeonpea. Alignment of these Illumina reads with respective transcriptome assemblies have
provided >10,000 SNPs each in chickpea and pigeonpea. A variety of SNP genotyping platforms including
GoldenGate, VeraCode and Competitive Allele Specific PCR (KASPar) assays have been developed in
chickpea and pigeonpea. By using above resources, the first-generation or comprehensive genetic maps have
been developed in the three legume speciesmentioned above. Analysis of phenotyping data together with genotyping data
has provided candidate markers for drought-tolerance-related root traits in chickpea, resistance to foliar diseases in
groundnut and sterility mosaic disease (SMD) and fertility restoration in pigeonpea. Together with these traitassociated
markers along with those already available, molecular breeding programmes have been initiated for
enhancing drought tolerance, resistance to fusarium wilt and ascochyta blight in chickpea and resistance to
foliar diseases in groundnut. These trait-associated robust markers along with other genomic resources including
genetic maps and genomic resources will certainly accelerate crop improvement programmes in the SAT legum
Identification of a non-redundant set of 202 in silico SSR markers and applicability of a select set in chickpea (Cicer arietinum L.)
Chickpea
The narrow genetic base of cultivated chickpea warrants systematic collection,
documentation and evaluation of chickpea germplasm and particularly wild
Cicer species for effective and efficient use in chickpea breeding programmes.
Limiting factors to crop production, possible solutions and ways to overcome
them, importance of wild relatives and barriers to alien gene introgression and
strategies to overcome them and traits for base broadening have been discussed.
It has been clearly demonstrated that resistance to major biotic and abiotic
stresses can be successfully introgressed from the primary gene pool
comprising progenitor species. However, many desirable traits including high
degree of resistance to multiple stresses that are present in the species
belonging to secondary and tertiary gene pools can also be introgressed by
using special techniques to overcome pre- and post-fertilization barriers.
Besides resistance to various biotic and abiotic stresses, the yield QTLs have
also been introgressed from wild Cicer species to cultivated varieties. Status
and importance of molecular markers, genome mapping and genomic tools
for chickpea improvement are elaborated. Because of major genes for various
biotic and abiotic stresses, the transfer of agronomically important traits into
elite cultivars has been made easy and practical through marker-assisted
selection and marker-assisted backcross. The usefulness of molecular markers
such as SSR and SNP for the construction of high-density genetic maps of
chickpea and for the identification of genes/QTLs for stress resistance, quality
and yield contributing traits has also been discussed
Ayurvedic management of Corneal Ectasia - A Conceptual Study
Corneal ectasia is a disorder that results in thinning of the central, paracentral, or peripheral cornea that leads to progressive myopia and irregular astigmatism. Keratoconus, Pellucid marginal corneal degeneration (PMCD), Terrien's marginal degeneration (TMD), Keratoglobus, Posterior keratoconus are the conditions/types of corneal ectatia. In Ayurveda there is no direct reference of corneal ectasia, based on signs and symptoms it can be correlated with Vataja Timira. Timira is the Drustigata Roga which further leads to Linganasha if not treated initially. Based on symptoms and Dosha-Dushya involvement Brhumhana and Vatahara line of treatment should be followed in the form of Virechana, Nasya, Tarpana, Putapaka and Pindi. These treatment modalities are more beneficial in corneal ectasia
The central region of meso-3,4-diphenylhexane-2,5-dione
As with 1,2-diphenylethane (dpe), X-ray crystallographic methods measure the central bond in meso-3,4-diphenylhexane-2,5-done (dphd) as significantly shorter than normal for an sp(3)-sp(3) bond. The same methods measure the benzylic (ethane C-Ph) bonds in dphd as unusually long for sp(3)-sp(2) liaisons. Torsional motions of the phenyl rings about the C-Ph bonds have been proposed as the artifacts behind the result of a 'short' central bond in dpe. While a similar explanation can, presumably, hold for the even 'shorter' central bond in dphd, it cannot account for the 'long' C-Ph bonds. The phenyl groups, departing much from regular hexagonal shape, adopt highly skewed conformations with respect to the plane constituted by the four central atoms. It is thought that-the thermal motions of the phenyl rings, conditioned by the potential wells in which they are ensconced in the unit cell, are largely libratory around their normal axes. In what appears to be a straightforward explanation under the 'rigid-body' concept, it appears that these libratory motions of the phenyl rings, that account, at the same time, for the 'short' central bond, are the artifacts behind the 'long' measurement of the C-Ph bonds. These motions could be superimposed on torsional motions analogous to those proposed in the case of dpe. An inspection of the ORTEP diagram from the 298 K data on dphd clearly suggests these possibilities. Supportive evidence for these qualitative explanations from an analysis of the differences between the mean square displacements of C(1) and C(7)/C(1a) and C(7a) based on the 'rigid-body model' is discussed. (C) 2002 Elsevier Science B.V. All rights reserved
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