Central Drug Research Institute

About: Central Drug Research Institute is a facility organization based out in Lucknow, Uttar Pradesh, India. It is known for research contribution in the topics: Catalysis & Leishmania donovani. The organization has 4357 authors who have published 7257 publications receiving 143871 citations. The organization is also known as: Central Drug Research Institute, Lucknow & CDRI.

Mitochondria Permeability Transition versus Necroptosis in Oxalate-Induced AKI.

Abstract: Background Serum oxalate levels suddenly increase with certain dietary exposures or ethylene glycol poisoning and are a well known cause of AKI. Established contributors to oxalate crystal–induced renal necroinflammation include the NACHT, LRR and PYD domains-containing protein-3 (NLRP3) inflammasome and mixed lineage kinase domain-like (MLKL) protein–dependent tubule necroptosis. These studies examined the role of a novel form of necrosis triggered by altered mitochondrial function. Methods To better understand the molecular pathophysiology of oxalate-induced AIK, we conducted in vitro studies in mouse and human kidney cells and in vivo studies in mice, including wild-type mice and knockout mice deficient in peptidylprolyl isomerase F (Ppif) or deficient in both Ppif and Mlkl. Results Crystals of calcium oxalate, monosodium urate, or calcium pyrophosphate dihydrate, as well as silica microparticles, triggered cell necrosis involving PPIF–dependent mitochondrial permeability transition. This process involves crystal phagocytosis, lysosomal cathepsin leakage, and increased release of reactive oxygen species. Mice with acute oxalosis displayed calcium oxalate crystals inside distal tubular epithelial cells associated with mitochondrial changes characteristic of mitochondrial permeability transition. Mice lacking Ppif or Mlkl or given an inhibitor of mitochondrial permeability transition displayed attenuated oxalate-induced AKI. Dual genetic deletion of Ppif and Mlkl or pharmaceutical inhibition of necroptosis was partially redundant, implying interlinked roles of these two pathways of regulated necrosis in acute oxalosis. Similarly, inhibition of mitochondrial permeability transition suppressed crystal-induced cell death in primary human tubular epithelial cells. PPIF and phosphorylated MLKL localized to injured tubules in diagnostic human kidney biopsies of oxalosis-related AKI. Conclusions Mitochondrial permeability transition–related regulated necrosis and necroptosis both contribute to oxalate-induced AKI, identifying PPIF as a potential molecular target for renoprotective intervention.

Short report: fluorescent Leishmania: application to anti-leishmanial drug testing.

Abstract: Classic techniques for detecting the susceptibility of Leishmania to different drugs are time-consuming, laborious, and require the use of macrophages. The use of flow cytometry for monitoring Leishmania susceptibility to drugs is beginning to be implemented. Using green fluorescent protein (GFP), we have improved and simplified the screening procedure. We introduced a GFP marker into field strains of Leishmania causing kala-azar (visceral leishmaniasis) and explored the suitability of transgenic L. donovani promastigotes that constitutively express GFP in their cytoplasm as target cells for in vitro screening of anti-leishmanial drugs.

Isolation and identification of a new antibacterial entity from the Antarctic cyanobacterium Nostoc CCC 537

Abstract: The present study was aimed at the isolation, purification and structural elucidation of an antibacterial entity/lead molecule from the Antarctic cyanobacterium Nostoc CCC 537. A methanolic extract of the cyanobacterium was bioassayed with Enterobacter aerogenes as a target. The extract was purified by TLC, and the most active band was subjected to HPLC. The fraction (retention time 15.7 min) designated as the active principle was antibacterial towards Gram positive Mycobacterium tuberculosis H37Rv, Staphylococcus aureus ATCC 25923, Gram negative Salmonella typhi MTCC 3216, Pseudomonas aeruginosa ATCC 27853, Escherichia coli ATCC 25992, Enterobacter aerogenes MTCC 2822 and multi-drug resistant strains of Escherichia coli GS 2003/01, 02, 03. Based on UV, IR, 1H NMR, EIMS, and ESIMS data, the structure of the active principle is proposed as 4-[(5-carboxy-2-hydroxy)-benzyl]-1,10-dihydroxy-3,4,7,11,11-pentamethyloctahydrocyclopenta naphthalene (Mr 428, Mp 243–249°C). This intracellular biomolecule is similar to anthraquinone and indane derivatives of a diterpenoid. The rate of production of the active principle currently corresponds to 1.70 mg g−1 biomass dry weight. The inherent property of Nostoc sp. to synthesise niche-specific biomolecules/lead molecules may be exploited for future drug development.