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A series of novel hybrid 4-aminoquinoline 1,3,5-triazine derivatives was synthesized in a five-steps reaction and evaluated for their in vitro antimalarial activity against chloroquine-sensitive (3D7) and chloroquine-resistant (RKL-2) strains of Plasmodium falciparum. Entire synthetic derivatives showed higher antimalarial activity on the sensitive strain while two compounds, viz., 9a and 9c displayed good activity against both the strains of P. falciparum. The observed activity was further substantiated by docking study on both wild and qradruple mutant type P. falciparum dihydrofolate reductase-thymidylate synthase (pf-DHFR-TS)., (Copyright © 2015 Elsevier Inc. All rights reserved.)

A new series of hybrid 4-aminoquinoline-1,3,5-triazine derivatives was synthesized by a four-step reaction. Target compounds were screened for in vitro antimalarial activity against chloroquine-sensitive (3D-7) and chloroquine-resistant (RKL-2) strains of Plasmodium falciparum. Compounds exhibited, by and large, good antimalarial activity against the resistant strain, while two of them, that is 8g and 8a, displayed higher activity against both the strains of P. falciparum. Additionally, docking study was performed on both wild (1J3I.pdb) and quadruple mutant (N51I, C59R, S108 N, I164L, 3QG2.pdb) type pf-DHFR-TS to highlight the structural features of hybrid molecules., (© 2014 John Wiley & Sons A/S.)

Reaction of Cu(II) complex [Cu(II)(LH)(O2CCH3)2] (1) [LH = 4,6-ditert-butyl-2-((2-picolyl(isopropyl)amino)methyl)phenol] with equivalent amount of NO2 leads to the reduction of Cu(II) to Cu(I) with concomitant nitration at the phenol ring of the ligand. This resulted in the in situ formation of intermediate Cu(I) complex of the nitrated ligand (L'H). Additional equivalent of NO2 coordinates to the Cu(I) complex to form corresponding O-nitrito Cu(II) complex [Cu(II)(L'(η(1)-ONO)] (2). Subsequent addition of NO2 led to the corresponding O-nitrato complex, [Cu(II)(L')(η(1)-ONO2)] (3) with concomitant formation of NO. Complexes 2 and 3 were isolated and structurally characterized. The formation of NO in the reaction was established by spin-trapping experiment. Isotopic labeling experiment revealed that the oxo transfer takes place from NO2 to the coordinated η(1)-ONO group.

The populations residing near polluted sites are more prone to various types of diseases. The important causes of air pollution are the suspended particulate matter, respirable suspended particulate matter, sulfur dioxide and nitrogen dioxide. As limited information is available enumerating the effect of these pollutants on liver physiology of the population living near the polluted sites; in the present study, we tried to investigate their effect on liver of the population residing near the oil drilling sites since birth. In this study, a randomly selected 105 subjects (46 subjects from oil drilling site and 61 subjects from control site) aged above 30 years were taken under consideration. The particulate matter as well as the gaseous pollutants, sulfur dioxide and nitrogen dioxide, were analyzed through a respirable dust sampler. The level of alkaline phosphatase, alanine transaminase and aspartate transaminase enzymes in serum were measured by spectrophotometer. The generalized regression model studies suggests a higher concentration of respirable suspended particulate matter, suspended particulate matter and nitrogen dioxide lowers the alkaline phosphatase level (p<0.0001) by 3.5 times (95% CI 3.1-3.9), 1.5 times (95% CI 1.4-1.6) and 12 times (95% CI 10.74-13.804), respectively in the exposed group. The higher concentration of respirable suspended particulate matter and nitrogen dioxide in air was associated with increase in alanine transaminase level (p<0.0001) by 0.8 times (95% CI 0.589-1.049) and by 2.8 times (95% CI 2.067-3.681) respectively in the exposed group. The increase in nitrogen dioxide level was also associated with increase in aspartate transaminase level (p<0.0001) by 2.5 times (95% CI 1.862-3.313) in the exposed group as compared to control group. Thus, the study reveals that long-term exposure to the environmental pollutants may lead to liver abnormality or injury of populations living in polluted sites.

Plant growth promoting rhizobacteria (PGPR) are beneficial rhizobacteria which enhance plant growth as well as the productivity by a variety of mechanisms PGPR were isolated from the rhizosphere region of som plants (Machilus bombycina King) maintained at the Central Muga Eri Research and Training Institute, Lahdoigarh, Jorhat. A bacterial based bioformulation was prepared and sprayed over the experimental crops including tomato (Solanum lycopersicum), cauliflower (Brassica oleracea var botrytis), chili (Capsicum annuum) and brinjal (Solanum melongena). Biochemical analysis was done on these PGPR treated crops as well as the untreated crops. The bioformulations prepared from Bacillus cereus (MTCC 8297), Pseudomonas rhodesiae (MTCC 8299) and Pseudomonas rhodesiae (MTCC 8300) was found to be the most effective in increasing the shoot height, number of leaves, early fruiting and total biomass content of the plants after treatment.

RNA interference (RNAi) has great potential to treat human disease. However, in vivo delivery of short interfering RNAs (siRNAs), which are negatively charged double-stranded RNA macromolecules, remains a major hurdle. Current siRNA delivery has begun to move away from large lipid and synthetic nanoparticles to more defined molecular conjugates. Here we address this issue by synthesis of short interfering ribonucleic neutrals (siRNNs) whose phosphate backbone contains neutral phosphotriester groups, allowing for delivery into cells. Once inside cells, siRNNs are converted by cytoplasmic thioesterases into native, charged phosphodiester-backbone siRNAs, which induce robust RNAi responses. siRNNs have favorable drug-like properties, including high synthetic yields, serum stability and absence of innate immune responses. Unlike siRNAs, siRNNs avidly bind serum albumin to positively influence pharmacokinetic properties. Systemic delivery of siRNNs conjugated to a hepatocyte-specific targeting domain induced extended dose-dependent in vivo RNAi responses in mice. We believe that siRNNs represent a technology that will open new avenues for development of RNAi therapeutics.

Background: COPD may develop due to variation in the functioning of antioxidants along with smoking and environmental factors in genetically susceptible individuals. Since there are different views about the antioxidants responsible for detoxifying xenobiotic compound in the human body whose functional variation may lead to obstructive disease, this associative study has been taken up between GST gene polymorphism and COPD in populations exposed to coal dusts., Methods: Genotypes of the 70 COPD patients and 85 non COPD patients were determined by PCR based methods followed by multiplex PCR of GSTT1 and GSTM1 genes taking albumin gene as a control. Suspended particulate analyses were determined through the Respirable Dust sampler along with the FTIR analysis of the dust samples from the glass microfiber filters., Results: Dust sampling analysis reveals higher level of respirable suspended particulate matter, non respirable particulate matter, SO2 and NO2 present in air of the study site. FTIR analysis also suggests a higher concentration of organic silicone and aliphatic C-F compounds present in air of the study site and when spirometry was done, low lung function was observed among most of the subjects. GSTM1 null type was significantly associated with low lung function in smoker groups and the presence of at least one active allele (either GSTM1/GSTT1) seemed to have a protective role in the development of COPD., Conclusions: GSTM1 (null genotype) appeared to be a risk factor for lower lung function in smokers living in the vicinity of coal mines. Apart from polluted environment and genetic susceptibility, mixed coal dust exposure rich in organic silicone and aliphatic C-F compounds also appears to be a factor for the low lung function.

Aims: To describe liquefied after cataract (LAC) and its surgical management following an uneventful phacoemulsification with posterior chamber in-the-bag intraocular lens (IOL) implantation and continuous curvilinear capsulorrhexis (CCC)., Design: Interventional case series., Materials and Methods: Eleven patients with LAC, following uneventful phacoemulsification with CCC and in-the-bag IOL implantation were enrolled. After the basic slit lamp examination, each case was investigated with Scheimpflug photography and ultrasound biomicroscopy (UBM). Each case was treated with capsular lavage. Biochemical composition of the milky fluid was evaluated and ring of anterior capsular opacity (ACO) was examined under electron microscope., Results: All 11 cases presented with blurring of vision after 6-8 years of cataract surgery with IOL implantation. All cases had IOL microvacuoles, 360° anterior capsule, and anterior IOL surface touch along with ACO, ring of Soemmering, and posterior capsule distension filled with opalescent milky fluid with whitish floppy or crystalline deposits. Biochemically, the milky fluid contained protein (800 mg/dl), albumin (100 mg/dl), sugar (105 mg/dl), and calcium (0.13%) and was bacteriologically sterile. Histologically, the dissected ACO showed fibrous tissue. All cases were successfully treated with capsular lavage with good visual recovery and with no complication. There was no recurrence of LAC during 2 years postoperative follow-up in any of the cases., Conclusions: LAC is a late complication of standard cataract surgery. It may be a spectrum of capsular bag distension syndrome (CBDS) without shallow anterior chamber and secondary glaucoma. Capsular bag lavage is a simple and effective treatment for LAC and a safe alternative to neodymium-doped yttrium aluminum garnet (Nd-YAG) capsulotomy.

Cellulose from Musa balbisiana was purified. A part of it was dispersed in distilled water using ultrasonication. The silver nanoparticles (SNP) were synthesized in the colloidal cellulose solution and stability of the nanoparticles was tested using UV-Vis spectrophotometer. Further characterization of the composite was done using spectral analysis by Fourier Transform Infrared Spectroscopy (FTIR) to reveal any bond formation between silver nanoparticles with M. balbisiana cellulose. Here we found that cellulose/silver nanoparticle colloid is stable for 29 days and there is no chemical interaction of cellulose with silver nanoparticles., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Cryopreservation of the threatened orchid Cymbidium eburneum L. was successfully achieved using encapsulation-vitrification and vitrification. Comparing the two methods tested, it was observed that regeneration of protocorms cryopreserved using encapsulation-vitrification was higher than with vitrification. To achieve optimal regrowth after cryopreservation, protocorms were precultured for 24 h with 0.2 M sucrose for vitrification and with 0.7 M sucrose for encapsulation-vitrification, reaching 60 percent and 70 percent regeneration, respectively. With both techniques employed, a 20 min exposure duration to Plant Vitrification Solution 2 (PVS2) led to optimal regeneration after cryopreservation. A maximum of 66 percent regeneration was achieved after cryopreservation using encapsulation-vitrification, whereas it was only 50 percent after cryopreservation using vitrification. The same regeneration pattern was observed with protocorms cryopreserved using both techniques employed. This is the first report of long-term conservation by cryopreservation of C. eburneum protocorms.

Present communication deals with the docking study of hybrid phenyl thiazolyl-1,3,5-triazine analogues (1a-36d) on three selected different binding site viz., α, β and γ of wild type Pf-DFHR-TS. In admiration of excellent H-bond scoring, with regard to cycloguanil and to a large extent similar scoring with WR99210, compound 4a, 12b, 21c, 23c, 28d, 29d, 34d, and 35d were selected for in vitro antimalarial activity against 3D7 strain of Plasmodium falciparum. Findings from the study disclose that a significant correlation was exist between in vitro results and in silico prediction (r(2)=0.543). Furthermore, investigation of structure-activity relationships elucidate crucial structural requirement for site specific binding of ligands., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Subtle differences in RNA and DNA duplex geometry could be sensed by the changed stereochemistry at 3'-amino function in the 5-atom thioacetamido linker of thioacetamido-linked nucleic acids and iso-thioacetamido-linked nucleic acids modified oligomers. In contrast to the preferred N-type sugar conformations for either 3'- ribo- or xylo amino nucleosides, predominant S-type sugar conformations were found in the dimers. Although the CD spectral differences for the dimer blocks were found to be identical for those found in phosphodiester linked ribo/xylo dimers, the 5-atom thioactamido linker could reverse the RNA binding selectivity to DNA binding selectivity by the change in configuration at the 3'-amino-substituted sugar.

Intracellular delivery of functional macromolecules using peptide transduction domains (PTDs) is an exciting technology with both experimental and therapeutic applications. Recent data indicate that PTD-mediated transduction occurs via fluid-phase macropinocytosis involving an intracellular pH drop to approximately 5. Nitrilotriacetic acid (NTA)-coordinated metals avidly bind hexahistidine-tagged macromolecules, including peptides and proteins. Histidine's imidazole ring has a pK(a) of 6, making this an attractive target for the biological pH drop of PTD-mediated macropinocytotic delivery. The objective of this study was to develop a pH-sensitive PTD delivery peptide (NTA(3)-PTD). We demonstrate the in vitro function of this novel peptide by delivering fluorescently labeled peptides (1.6 kDa) and functional enzymes, beta-galactosidase (119 kDa) and Cre recombinase (37 kDa). Furthermore, the NTA(3)-PTD peptide was able to deliver functional Cre recombinase in an in vivo mouse model.

An alpha/beta-peptide backbone oligonucleotide comprising natural alpha-amino acids alternating with a beta-amino acid component derived from thymidine sequence specifically recognizes and binds to deoxy- and ribo-oligoadenylates in triplex mode.

Purpose: To determine the pattern of bacteriology of chronic dacryocystitis in the Northeast Indian population and compare it with previous studies., Methods: A prospective analysis of 543 lacrimal sac content of 421 patients in the period of October 2003 to June 2007. Material obtained directly from the lacrimal sac during making sac flap that had undergone external dacryocystorhinostomy for chronic dacryocystitis., Results: Five hundred eighty-four bacteria were isolated from 543 specimens of 421 patients. Growths were observed in 494 (90.97%) specimens, and there was no growth in 49 (9.03%) of the specimens; 61.04% were female and 38.95% were male. Four hundred ninety-four samples (90.97%) were positive for bacteria, including both single and mixed isolations. Four hundred five (74.58%) had single isolations, 89 (16.39%) patients had mixed bacterial isolations (more than one organism), and no organisms were isolated from 49 (9.02%) specimens. The majority of microorganisms in our study were gram-positive bacteria, 75% of the overall microorganisms cultured were gram-positive bacteria, with a predominance of staphylococcus species. Gram-negative bacteria were isolated in 25% of the specimens with predominance of Pseudomonas aeruginosa., Conclusions: It is important to have knowledge of the microbial organisms responsible for chronic dacryocystitis in a particular geographical area to choose the prophylactic antibiotic following lacrimal drainage procedure. Identification of the microbes and proper antibiotic prophylaxis helps for the better management of the postoperative period.

Convenient chemical synthesis and incorporation of dithymidine and thymidine-cytidine dimer blocks connected with a five-atom amide linker N3'-CO-CH2-S-CH2 into oligonucleotides (ONs) are reported. The UV-Tm experiments for binding affinities of these mixed backbone ONs with complementary DNA and RNA sequences revealed important results such as significantly higher RNA-binding selectivity as compared with complementary DNA. NMR studies of the dimer blocks suggested a marginal increase in the N-type sugar conformations over that of the native DNA.

The specific 1,3 dipolar Hüisgen cycloaddition reaction known as 'click-reaction' between azide and alkyne groups is employed for the synthesis of peptide-oligonucleotide conjugates. The peptide nucleic acids (PNA)/DNA and peptides may be appended either by azide or alkyne groups. The cycloaddition reaction between the azide and alkyne appended substrates allows the synthesis of the desired conjugates in high purity and yields irrespective of the sequence and functional groups on either of the two substrates. The versatile approach could also be employed to generate the conjugates of peptides with thioacetamido nucleic acid (TANA) analog. The click reaction is catalyzed by Cu (I) in either water or in organic medium. In water, approximately 3-fold excess of the peptide-alkyne/azide drives the reaction to completion in 2 h with no side products.

The amide linkage being shorter than the natural phosphate linkage, an additional atom is introduced into oligodeoxyribonucleosides (ODNs) with sugar-thioacetamide backbone that show very good RNA recognition properties.