Sequence Analysis of Rifampicin Resistance Determining Region (RRDR) of Mycobacterium Tuberculosis

Mycobacterium tuberculosis has become the cause for one of the most dreadful disease which the mankind has ever known i.e. Tuberculosis. The organism holds the ability to infect multiple organs at a time resulting in multiple symptomatic presentations in pathogenic condition while in non-pathogenic condition, it can lay dormant and remain asymptomatic. The research work presented here aimed at sequencing of Rifampicin Resistance Determining Region (RRDR) of the rpoB gene present in phenotypically multidrug resistant M. tuberculosis. The findings showed that the major point of mutations to be present within this region was at codon 516, 526, and 531. Early diagnosis of multidrug resistance in any pathogen has become a pre – requisite for proper treatment and efficient elimination of pathogenic organisms from the host with minimal toxicity. Similarly, understanding the mutation dynamics of target genes also help in novel drug design and discovery

Rare association of Visceral leishmaniasis with Hodgkin's disease: A case report

We present here a case of young male with complaints of fever and swelling in the neck for eight months. History of progressive weakness associated with weight loss was present. Physical examination revealed pallor, multiple enlarged cervical lymph nodes and hepatosplenomegaly. Investigations showed pancytopenia, hyperglobinemia and Leishman-Donovan bodies on bone marrow aspiration. Serological test confirmed diagnosis of visceral leishmaniasis. However, cervical lymph node aspiration and biopsy were suggestive of Mixed cellularity Hodgkin's disease. This made it a very rare case of Leishmaniasis as an opportunistic infection in a patient of pre-chemotherapy Hodgkin's disease. There was marked improvement in haematological profile and regression of hepatosplenomegaly with Amphotericin B treatment followed by favourable response to chemotherapy. The case emphasizes the suspicion for leishmaniasis as a masquerader and as an opportunistic infection in haematological malignancies

Mitochondria-Dependent Reactive Oxygen Species-Mediated Programmed Cell Death Induced by 3,3�-Diindolylmethane through Inhibition of F0F1-ATP Synthase in Unicellular Protozoan Parasite Leishmania donovan

Mitochondria are the principal site for the generation of cellular ATP by oxidative phosphorylation. F0F1-ATP synthase, a complex V of the electron transport chain, is an important constituent of mitochondria-dependent signaling pathways involved in apoptosis. In the present study, we have shown for the first time that 3,3�-diindolylmethane (DIM), a DNA topoisomerase I poison, inhibits mitochondrial F0F1-ATP synthase of Leishmania donovani and induces programmed cell death (PCD), which is a novel insight into the mechanism in protozoan parasites. DIM-induced inhibition of F0F1-ATP synthase activity causes depletion of mitochondrial ATP levels and significant stimulation of mitochondrial reactive oxygen species (ROS) production, followed by depolarization of mitochondrial membrane potential (��m). Because ��m is the driving force for mito mitochondrial ATP synthesis, loss of ��m results in depletion of cellular ATP level. The loss of ��m causes the cellular ROS generation and in turn leads to the oxidative DNA lesions followed by DNA fragmentation. In contrast, loss of ��m leads to release of cytochrome c into the cytosol and subsequently activates the caspase-like proteases, which lead to oligonucleosomal DNA cleavage. We have also shown that mitochondrial DNA-depleted cells are insensitive to DIM to induce PCD. Therefore, mitochondria are necessary for cytotoxicity of DIM in kinetoplastid parasites. Taken together, our study indicates for the first time that DIM-induced mitochondrial dysfunction by inhibition of F0F1-ATP synthase activity leads to PCD in Leishmania spp. parasites, which could be exploited to develop newer potential therapeutic targets

A novel spirooxindole derivative inhibits the growth of Leishmania donovani parasite both in vitro and in vivo by targeting type IB topoisomerase

Visceral Leishmaniasis is a fatal parasitic disease and there is an emergent need for development of effective drugs against this neglected tropical disease. We report here development of a novel spirooxindole derivative N-benzyl 2, 2’ α 3, 3’, 5’, 6’, 7’, 7α,α'-octahydro-2methoxycarbonyl-spiro [indole-3, 3’ -pyrrolizidine]-2 one (Compound 4c) which inhibits Leishmania donovani topoisomerase IB (LdTopIB) and kills the wild type as well as drug-resistant parasite strains. This compound inhibits catalytic activity of LdTopIB in competitive manner. Unlike Camptothecin, the compound does not stabilize the DNA-topoisomerase IB cleavage complex; rather, they hinder drug-DNA-enzyme covalent complex formation. Fluorescence studies show stoichiometry of this compound binding to LdTopIB is 2:1 (mole/mole) with a dissociation constant of 6.65 μM. Molecular docking with LdTopIB using the stereoisomers of Compound 4c produced two probable hits for binding site: one in small subunit and the other in the hinge region of the large subunit of LdTopIB. This spirooxindole is highly cytotoxic to promastogotes of L. donovani and also induces apoptosis-like cell death in parasite. Treatment with compound 4c causes depolarization of mitochondrial membrane potential, formation of reactive oxygen species inside parasites and ultimately fragmentation of nuclear DNA. Compound 4c also effectively clears amastigote forms of wild type and drug-resistant parasites from infected mouse peritoneal macrophages but has less effect on host macrophages. Moreover compound 4c showed strong antileishmanial efficacies in BALB/c mice model of leishmaniasis. Potentially this compound can be used as a lead for developing excellent anileishmanial agent against emerging drug resistant strains of the parasite

Evaluation of Phytochemical Parameters, Antibacterial and Antihelminthic Activity of Leaves and Bark Extracts of Plant Bombax Ceiba

Bombax ceiba, commonly known as the red silk-cotton tree, is a large, briefly deciduous tree occurring in warm monsoon forests in southern Asia. Various phytochemical constituents present in different plant parts has been already reported earlier to possess many biological activities, here in this work extraction was performed by mixture of solvent (distilled water: ethanol) as well as the individual solvents (water) and (ethanol). The phytochemical screening of the leaves and barks was found to exhibit the presence of carbohydrates, glycoside, saponin, phytosterol phenol, tannins, flavonoid, proteins and diterpenes and negative result for alkaloids in all the solvent extracts. The ethanolic extract of leaves was subjected to antihelmenthic activity and the result was found to be moderat