In vitro and in vivo antiplasmodial activity of the root extracts of Brucea mollis Wall. ex Kurz.

Malaria control is compromised worldwide by continuously evolving drug-resistant strains of the parasite demanding exploration of natural resources for developing newer antimalarials. The northeastern region of India is endemic for malaria characterized by high prevalence of drug-resistant Plasmodium falciparum strains. Many plants are used by the indigenous communities living in the northeast India in their traditional system of medicine for the treatment of malarial fever. Folklore claim of antimalarial property of one such plant Brucea mollis was evaluated in vitro and in vivo for antiplasmodial activity. Crude extracts from dried B. mollis root powder were prepared through soxhlet extraction using petroleum ether, methanol, and water sequentially. Methanol extract was further partitioned between chloroform and water. These extracts were tested in vitro against laboratory-adapted chloroquine-sensitive and chloroquine-resistant strains of P. falciparum. In in vitro evaluation, extracts were found more active on the chloroquine-sensitive strain. Methanolic-chloroform (IC(50) 5.1 µg ml(-1)) and methanolic-aqueous (IC(50) 13.9 µg ml(-1)) extracts recorded significant in vitro antiplasmodial activity which was also supported by their promising in vivo activity (ED(50) 72 and 30 mg kg(-1) bw day(-1), respectively) against chloroquine-resistant Plasmodium yoelli N-67 strain in Swiss albino mice. Methanolic-aqueous extract-treated mice survived on average for 14 days that was comparable to the reference drug chloroquine. This is the first report of antiplasmodial activity of B. mollis validating the traditional use of this plant as antimalarial in the northeast India and calls for further detailed investigations.

In vitro antimalarial activity and molecular docking analysis of 4-aminoquinoline-clubbed 1,3,5-triazine derivatives.

AIMS: Present report describes the in vitro antimalarial activity and docking analysis of seven 4-aminoquinoline-clubbed 1,3,5-triazine derivatives on pf-DHFR-TS. METHODS AND RESULTS: The antimalarial activity was evaluated in vitro against chloroquine-sensitive 3D7 strain of Plasmodium falciparum. Compounds were docked onto the active site of pf-DHFR-TS using docking server to explicate necessary structural requirements for antimalarial activity. CONCLUSION: Title molecules demonstrated considerable bioactivity against the malaria parasite. Docking analysis revealed deep engulfment of the molecules into the inner groove of pf-DHFR-TS active site by making stable ligand-receptor posses. Hydrophobic interaction was identified as the only major interacting force playing a role between ligand-receptor interaction and minor with hydrogen bonds. SIGNIfiCANCE AND IMPACT OF THE STUDY: The study provided the novel insight into the necessary structural requirement for rationale-based antimalarial drug discovery.

A comparative study of vitrification and encapsulation-vitrification for cryopreservation of protocorms of Cymbidium eburneum L., a threatened and vulnerable orchid of India.

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.

Effects for the incorporation of five-atom thioacetamido nucleic acid (TANA) backbone on hybridization thermodynamics and kinetics of DNA duplexes.

Thermodynamic studies of nucleic acids serve not only to widen our understanding on the nature and strength of forces that stabilize nucleic acids in a myriad of structural states they assume but also to facilitate the development of databases that could be used to predict the stability and selectivity of probe/primer-sets required in a broad range of nucleic acid-based diagnostic and therapeutic protocols. In the current study, we investigated the effect of a novel, backbone-modified "thioacetamido linkage" (TANA) on thermodynamics of hybridization, binding kinetics, and conformation of a DNA duplex. The modification comprises of an extended five-atom amide (N3'-CO-CH2-S-CH2) linker, as opposed to four-atom phosphodiester linker backbone present in DNA. One to three TANA-substitutions have been introduced in the linker backbone of two thymidine residues of one of the strand of the DNA duplex. Using spectroscopic and calorimetric techniques, we observed that TANA destabilizes the DNA helix by lowering the favorable enthalpy parameter of duplex formation. TANA x DNA duplexes were found to adopt a conformation toward an A-type duplex as shown by circular dichroism spectroscopy studies. Analysis of differential scanning calorimetry data indicated a nonzero heat capacity change, deltaCp, accompanying the duplex formation. The average deltaCp, change per duplex was found to be 832.5 cal mol(-1) K(-1), giving an average base-pair change of 59.5 cal (mol of base pairs)(-1) K(-1). Hybridization kinetic measurements using surface plasmon resonance indicated a decrease in binding affinity parameter (KA) that originates from higher dissociation rate constants (k(d)). Furthermore, optical melting studies showed that increasing the number of modifications results in a modest change in the number of counterions taken up during duplex formation.

Microbial profile of the vitreous aspirates in culture proven exogenous endophthalmitis: A 10-year retrospective study.

PURPOSE: To describe the microbiological profile and clinical outcome in the eyes with culture-proven exogenous endophthalmitis. METHODS: A retrospective analysis of 495 eyes diagnosed as exogenous endophthalmitis was performed over a period of 10 years. In all, aseptically collected aqueous and vitreous aspirates were cultured for bacteria and fungus using standard microbiological techniques. Gram-stain and KOH preparation of the specimens were also performed. The antibiotic susceptibility testing for bacterial isolates was performed by Kirby-Bauer disk diffusion method. The treatment was modified according to the antibiotic sensitivity profile. The final clinical ocular condition was divided into improved, stable or deteriorated. RESULTS: Of 148 culture-proven endophthalmitis eyes, 137 (92.57%) were referred from elsewhere, and 11 (7.43%) belonged to our institute. Aetiologically, 76 (51.35%) eyes were post-cataract surgery, 61 (41.22%) were post-traumatic, 5 (3.38%) eyes post-intravitreal anti-vascular endothelial growth factor injection, 5 associated with corneal diseases and 1 bleb-related endophthalmitis. In 31 (20.95%) eyes, primary intravitreal antibiotics were given outside. The cultures revealed monomicrobial growth in 92.57% (n = 137) and polymicrobial growth in 7.43% (n = 11). Among the bacteria (n = 121, 81.76%), Pseudomonas species dominated overall (n = 32, 27.11%) and post-operative (n = 26, 38.23%) endophthalmitis group. Staphylococcus epidermidis (n = 14, 28%) was prominent in post-traumatic endophthalmitis group. Ninety-two percent (n = 108 isolates) of bacteria were sensitive to vancomycin. In 78 (52.7%) eyes, the clinical ocular condition improved or remained stable while deteriorated in 51 (34.46%). CONCLUSION: A bacterial predominance was observed among causative organisms of exogenous endophthalmitis with Pseudomonas species being the most common. The appropriate surgical intervention improved or stabilised the visual acuity in nearly 50% eyes.

Larvicidal activity of few select indigenous plants of North East India against disease vector mosquitoes (Diptera: Culicidae).

Mosquitoes are the vectors of several life threatening diseases like dengue, malaria, Japanese encephalitis and lymphatic filariasis, which are widely present in the north-eastern states of India. Investigations on five local plants of north-east India, selected on the basis of their use by indigenous communities as fish poison, were carried out to study their mosquito larvicidal potential against Anopheles stephensi (malaria vector), Stegomyia aegypti (dengue vector) and Culex quinquefasciatus (lymphatic filariasis vector) mosquitoes. Crude Petroleum ether extracts of the roots of three plants viz. Derris elliptica, Linostoma decandrum and Croton tiglium were found to have remarkable larvicidal activity; D. elliptica extract was the most effective and with LC50 value of 0.307 µg/ml its activity was superior to propoxur, the standard synthetic larvicide. Half-life of larvicidal activity of D. elliptica and L. decandrum extracts ranged from 2-4 days.