Umakant Sharma

All India Institute of Medical Sciences, New Delhi, NCT, India

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Publications (11)16.74 Total impact

  • Sarman Singh, Umakant Sharma, Jyotsna Mishra
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    ABSTRACT: BACKGROUND AND OBJECTIVES: Because of the developing resistance of Mycobacterium species against currently available anti-mycobacterial drugs, there is an urgent need for new drug development. In this study, we have evaluated the in vitro anti-mycobacterial activity of Plumeria bicolor extract and its phytoconstituents- plumericin and isoplumericin against multi-drug resistance Mycobacterium tuberculosis. METHODS: The in vitro anti-mycobacterial activity of chloroform extract of Plumeria bicolor, plumericin and isoplumericin were tested against Mycobacterium tuberculosis (H37Rv) and four multi drug resistant (MDR) clinical isolates by measuring the minimum inhibitory concentration (MIC) using MTT (Tetrazolium bromide [3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide) assay. The extract and both compounds were further evaluated by standard assay procedures to determine their minimum bactericidal concentration (MBC). Cytotoxicity of these compounds was performed against J774G8 murine macrophage cell lines. The activity was represented in the mean (±SD) of duplicate samples from three independent assays. RESULTS: Plumericin showed better activity against pan sensitive as well as four MDR strains of M. tuberculosis with MIC values of 2.1±0.12, 1.3±0.15, 2.0±0.07, 1.5±0.13 & 2.0±0.14 μg/mL and MBC values of 3.6±0.22, 2.5±0.18, 3.8±0.27, 2.9±0.20 & 3.7±0.32 μg/mL than isoplumericin, respectively. Interestingly, both isolated active compounds showed an advantage over rifampicin (80 times) and isoniazid (8 times) by being highly active against the MDR strains. The extract and both compounds were found to be non toxic against J774G8 macrophages up to the used concentrations. CONCLUSION: Plumericin showed more potent activity than isoplumericin. The excellent activity of these compounds against MDR strains opens a possibility of obtaining new anti-mycobacterial drug candidate in near future.
    Pulmonary Pharmacology &amp Therapeutics 01/2013; · 2.54 Impact Factor
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    ABSTRACT: This study evaluated the in vitro antifungal activity of the chloroform extract of Plumeria bicolor and its phytoconstituents plumericin and isoplumericin against Candida species and Cryptococcus neoformans by measuring the Minimum Inhibitory Concentration (MIC) and Minimum Fungicidal Concentration (MFC). Plumericin's consistently high activity against Candida albicans, C. krusei, C. glabrata, C. tropicalis and Cryptococcus neoformans was more potent than isoplumericin and the standard antifungal drug nystatin suggesting its potential as a drug candidate for candidiasis and cryptococcosis.
    Natural product communications 11/2011; 6(11):1567-8. · 0.96 Impact Factor
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    ABSTRACT: The severe toxicity, exorbitant cost and emerging resistance of Leishmania species against most of the currently used drugs underscores the urgent need for the alternative drugs. The present study evaluates in vitro anti-leishmanial activity of Plumeria bicolor and its isolated compounds. The in vitro anti-parasitic activity of chloroform extract of Plumeria bicolor, plumericin and isoplumericin were tested alongwith appropriate controls against promastigote and amastigote forms of Leishmania donovani using 96 well microtiter plate. The concentration used for assessing the anti-leishmanial activity of extract of Plumeria bicolor and both isolated compounds were 100 μg/ml and 15 μM, respectively. The viability of the cells was assessed by MTT assay. The cytotoxicity of these compounds was performed against J774G8 murine macrophage cells lines at the concentration of 30 μM. The Plumeria bicolor extract showed activity with the IC 50 of 21±2.2 and 14±1.6 μg/ml against promastigote and amastigote forms of L. donovani, respectively. Plumericin consistently showed high activity with the IC 50 of 3.17±0.12 and 1.41±0.03 μM whereas isoplumericin showed the IC50 of 7.2±0.08 μM and 4.1±0.02 μM against promastigote and amastigote forms, respectively. Cytotoxic effect of the chloroform extract of P. bicolor, plumericin and isoplumericin was evaluated in murine macrophage (J774G8) model with CC50 value of 75±5.3 μg/ml, 20.6±0.5 and 24±0.7 μM, respectively. Our results indicated that plumericin showed more potent activity than isoplumericin and might be a promising anti-leishmanial agent against L. donovani.
    The Indian Journal of Medical Research 11/2011; 134(5):709-16. · 2.06 Impact Factor
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    Sarman Singh, Umakant Sharma, Jyotsna Mishra
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    ABSTRACT: A substantial number of patients who recover from kala-azar will develop dermatosis [commonly known as post-kala-azar dermal leishmaniasis (PKDL)]. It usually occurs in the Indian subcontinent and East Africa. As many as 10-20% of Indian cases and 50-60% of Sudanese cases develop PKDL after successful treatment of visceral leishmaniasis. Most cases occur after infection with Leishmania donovani and less commonly after Leishmania infantum. However, the PKDL is extremely rare in patients infected with Leishmania chagasi. Though exact pathology is not yet fully known, here we review various evidence, which suggest that the pathogenesis is largely immunologically mediated. Our group has been of the opinion that PKDL disease manifestation is a result of in-vivo generation of quasi-species either as in-vivo hybridization of various circulating and latent populations of the causative species within the host cells or due to external reinfection. We, and other scientists, have recently demonstrated that strains of Leishmania that cause visceral diseases differ genetically from those that cause PKDL. We feel that this review will incite interest in several parasitologists and molecular biologists in the pathogenesis of this important manifestation of the infection, often blamed as the source of outbreaks of leishmaniasis.
    International journal of dermatology 09/2011; 50(9):1099-108. · 1.18 Impact Factor
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    ABSTRACT: A substantial number of patients who recover from kala-azar will develop dermatosis [commonly known as post-kala-azar dermal leishmaniasis (PKDL)]. It usually occurs in the Indian subcontinent and East Africa. As many as 10–20% of Indian cases and 50–60% of Sudanese cases develop PKDL after successful treatment of visceral leishmaniasis. Most cases occur after infection with Leishmania donovani and less commonly after Leishmania infantum. However, the PKDL is extremely rare in patients infected with Leishmania chagasi. Though exact pathology is not yet fully known, here we review various evidence, which suggest that the pathogenesis is largely immunologically mediated. Our group has been of the opinion that PKDL disease manifestation is a result of in-vivo generation of quasi-species either as in-vivo hybridization of various circulating and latent populations of the causative species within the host cells or due to external reinfection. We, and other scientists, have recently demonstrated that strains of Leishmania that cause visceral diseases differ genetically from those that cause PKDL. We feel that this review will incite interest in several parasitologists and molecular biologists in the pathogenesis of this impor-tant manifestation of the infection, often blamed as the source of outbreaks of leishmaniasis.
    International Journal of Dermatology 01/2011; 2011(50):1099–1108. · 1.34 Impact Factor
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    ABSTRACT: The severe toxicity, exorbitant cost and the emerging resistance of Leishmania spp. against most of the currently used drugs led to the urgent need for exploiting our traditional Ayurvedic knowledge to treat visceral leishmaniasis. The aim of this study was to evaluate the in vitro anti-leishmanial activity of various extracts from ten traditionally used Indian medicinal plants. The methanolic extract from only two plants, Withania somnifera Dunal (ashwagandha) and Allium sativum Linn. (garlic), showed appreciable activity against Leishmania donovani. Further active compounds from these two plants were isolated and purified based on bioactivity-guided fractionation. HPLC-purified fraction A6 of ashwagandha and G3 of garlic showed consistently high activity with 50% inhibitory concentration (IC(50)) of 12.5 +/- 4 and 18.6 +/- 3 microg/ml against promastigotes whereas IC(50) of 9.5 +/- 3 and 13.5 +/- 2 microg/ml against amastigote form, respectively. The fraction A6 of ashwagandha was identified as withaferin A while fraction G3 of garlic is yet to be identified, and the work is in progress. Cytotoxic effects of the promising fractions and compounds were further evaluated in the murine macrophage (J774G8) model and were found to be safe. These compounds showed negligible cytotoxicity against J774G8 macrophages. The results indicate that fraction A6 of ashwagandha and fraction G3 of garlic might be potential sources of new anti-leishmanial compounds. The in vivo efficacy study and further optimization of these active compounds are in progress.
    Parasitology Research 08/2009; 105(5):1287-93. · 2.85 Impact Factor
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    Umakant Sharma, Sarman Singh
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    ABSTRACT: Leishmaniasis is a parasitic disease caused by various species of Leishmania, a unicellular kinetoplastid protozoan flagellate. It manifests mainly in 3 clinical forms; visceral leishmaniasis (VL), cutaneous leishmaniasis (CL) and mucocutaneous leishmaniasis (MCL), of which VL is the most severe form of the disease. VL is lethal if untreated and spontaneous cure is extremely rare. Cutaneous leishmaniasis usually has milder course and often results into a self-healing of ulcers. Resolution of leishmanial infection is dependent on the coordinated interactions between components of cell mediated immune response, specifically the activation of targeted T-cell populations for appropriate cytokine production and activation of macrophages. In murine model, the development of Thl response is associated with control of infection, and Th2 response is associated with disease progression. However, Th1 and Th2 dichotomy in the human system is not as distinct as in mice and the murine model does not strictly apply to human leishmaniasis. This review focuses the dichotomy of immune response against various clinical forms of the disease. An in-depth knowledge of sequences involved in the immune response to the parasite would help in designing prophylactic and therapeutic strategies against leishmaniasis.
    Indian journal of experimental biology 07/2009; 47(6):412-23. · 1.20 Impact Factor
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    Umakant Sharma, Sarman Singh
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    ABSTRACT: Leishmaniasis is a deadly vector-borne disease that causes significant morbidity and mortality in Africa, Asia, Latin America and Mediterranean regions. The causative agent of leishmaniasis is transmitted from man to man by a tiny insect called sandfly. Approximately, 600 species of sandflies are known but only 10% of these act as disease vectors. Further, only 30 species of these are important from public health point. Fauna of Indian sub-zone is represented by 46 species, of these, 11 belong to Phlebotomine species and 35 to Sergentomyia species. Phlebotomus argentipes is the proven vector of kala-azar or visceral leishmaniasis in India. This review gives an insight into the insect vectors of human leishmaniasis, their geographical distribution, recent taxonomic classification, habitat, and different control measures including indoor residual spraying (IRS), insecticide-treated bednets (ITNs), environmental management, biological control, and emerging resistance to DDT. Role of satellite remote sensing for early prediction of the disease by identifying the sandflygenic conditions cannot be undermined. The article also underlines the importance of synthetic pheromones which can be used in near future for the control of these vectors.
    Journal of vector borne diseases 01/2009; 45(4):255-72. · 1.04 Impact Factor
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    Journal of vector borne diseases 10/2007; 44(3):230-2. · 1.04 Impact Factor
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    Ayan Dey, Umakant Sharma, Sarman Singh
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    ABSTRACT: Visceral leishmaniasis is endemic in the eastern states of India, but central India remains free of leishmaniais. This report describes the first indigenous case of visceral leishmaniasis in a seven-year-old girl from central India. The child presented with fever for 10 days and was diagnosed by bone marrow examination, serology using rKE16 and rK39 antigens, and a polymerase chain reaction specific for the kinesin gene. Sequencing of the immunodominant region of the kinesin gene of the parasite showed four tandem repeats, each 117 basepairs. The first tandem repeat of this strain had 97% homology with the corresponding first tandem repeat of the Leishmania donovani KE16 strain and 92% homology with the L. chagasi BA-2 strain. The second, third, and fourth tandem repeats had 97%, 98%, and 99% homology, respectively, with the L. donovani KE16 strain, and 89%, 96%, and 92% homology, respectively, with the L. chagasi BA-2 strain. This case shows that more than one genetic variant of L. donovani is circulating in various parts of India.
    The American journal of tropical medicine and hygiene 08/2007; 77(1):95-8. · 2.53 Impact Factor